EVOLUTION, SCIENCE AND SOCIETY: version 2 [draft of February 1996, revised beginning April 2, 1996] [P] [PREAMBLE] [P-1] Three great themes run through the biological sciences: function, unity, and diversity. Much of biology, extending from molecular biology to behavioral biology, is concerned with the mechanisms by which organisms function. Many of these mechanisms are adaptations: features that enhance survival and reproduction. Some such features are found only in certain groups of organisms, and others characterize almost all living things, betokening the unity of life. At the same time, the diversity of characteristics among the earth's millions of species is staggering. [P-2] The unity, diversity, and adaptive characteristics of organisms, as well as features that are not adaptive, are the consequences of their evolutionary history, and can be understood fully only in this light. The science of evolutionary biology is the study of the history of life and the processes that have led to its unity and diversity. It provides explanations for the phenomena studied in molecular biology, developmental biology, physiology, behavior, and ecology, complementing these disciplines' study of mechanisms with explanations based on history and adaptation. Throughout the biological sciences, the evolutionary perspective has provided an important and sometimes indispensable framework for organizing and interpreting observations. [P-3] There is reason to believe that despite its centrality in the life sciences, evolutionary biology does not command prominence in educational curricula or in research funding commensurate with its intellectual contributions and its potential for contributing to social needs. The reasons for this may include a misperception that scientific questions about evolution have already been answered; a misperception that evolutionary biology is less modern and advanced a field than some more conspicuous disciplines; and the controversy among non-scientists about the reality of evolution and its perceived (but groundless) threat to traditional social values. Contrary to these perceptions, evolutionary biology is an intellectually and technologically dynamic discipline, which at present is undergoing some of the most exciting developments in the biological sciences. [P-4] This document is addressed mostly to decision-makers responsible for guiding basic and applied scientific research and for developing educational curricula, primarily but not exclusively at the college and university level. The major purposes of this document are (1) to describe our present understanding of evolution and some of the major intellectual accomplishments of evolutionary biology; (2) to identify some major questions and challenges in which progress in evolutionary science can be expected in the near future; (3) to describe some past and expected contributions of evolutionary biology both to other sciences and to meeting social needs in areas such as health science, agriculture, and environmental science; and (4) to suggest ways in which progress can be facilitated in basic research, development of applications of evolutionary biology to social needs, and education in biological science. [P-5] We conclude that (1) Evolutionary biology has made spectacular progress in answering many of its major questions, but that much remains to be done; (2) Evolutionary biology has made significant contributions to many other biological disciplines, but the potential for such contributions in certain areas has not been fully realized; (3) Knowledge and concepts from evolutionary biology have had many important social applications, but the potential for such applications is only beginning to be realized; (4) Various subdisciplines of evolutionary biology are intimately related to the missions of diverse funding agencies concerned with supporting both basic biological research and its applications to social needs; (5) Explicitly targeting such subdisciplines for research support is warranted; (6) Mechanisms for supporting interchange between evolutionary science and areas of applied research and development should be developed; (7) Increased emphasis on evolution is critically needed in science education, in both secondary education and college curricula; and (8) Evolutionary scientists should be more active in public outreach and education and in developing applications of their work to social needs. [P-6] This document has been prepared by delegates from all the major professional scientific societies in the United States whose subject matter substantially includes evolution. Contributions to the document have also been made by several other specialists in various topics. A draft of the document was revised in light of feedback elicited from the community of evolutionary biologists in the United States, by making the draft public at scientific meetings and on the Worldwide Web. Although full agreement cannot be expected on every detail and point of emphasis, the major points and conclusions in the following pages fairly represent a large majority of professional evolutionary biologists. [I] [INTRODUCTION] [I-1] "What a piece of work is man! The beauty of the world, the paragon of animals!" Like Shakespeare's Hamlet, we too marvel at the exquisite features of our species, but after four centuries we do so in the light of immensely greater knowledge. Reflect, for example, on the human body: a textbook of biology, a lesson in evolution. [I-2] We are struck, first, by the innumerable features that enable us to function. Whether we consider our eyes, brain, or immune system, we find complex features admirably suited for the functions they perform. Such features, serving survival and reproduction, are called adaptations. How did they come to be? [I-3] Looking more closely, though, we find anomalies that don't make adaptive sense. How do we account for our nonfunctional appendix, for nipples on men, for wisdom teeth that erupt painfully or not at all, or for the peculiar arrangement of our digestive and respiratory tracts, which inconveniently cross each other so that we are at risk of choking on food? [I-4] Considering our species at large, we see almost endless variation. Differences among people in size, shape, and pigmentation are the tip of the iceberg: almost everyone has unique facial features and unique DNA "fingerprints," there is hereditary variation in susceptibility to infectious diseases, and an unfortunate number of people inherit any of many rare genetic defects. What accounts for all this variation? [I-5] If we expand our view, and compare ourselves to other organisms, we find a range of features that we hold in common with increasingly broad ranges of other species. We are united with apes, monkeys, and lemurs by our fingernails, with all mammals by hair, milk, and the structure of our teeth and jaws, with reptiles, birds, and amphibians by the basic structure of our arms and legs, and with all vertebrates, including fish, by our vertebrae and many other features of our skeleton. Probing more deeply, we find that the structure of our cells unites us with all animals, and the biochemical functions of our cells, such as the way the cells' mitochondria use oxygen, are virtually identical across a still wider group of organisms, the eukaryotes: not only animals, but also plants, fungi, and protists such as amoebas. Most fundamental of all, the vehicle of heredity, DNA, the variety of amino acids that are the building blocks of proteins, the specific code in the DNA for each of these amino acids -- all these features are the same throughout the living world, from bacteria to mammals. Such commonalities among species demand explanation. [I-6] This world of species with which we hold so much in common: how extraordinarily diverse it is, despite its unity! Look at a back yard, a roadside ditch, or even an abandoned city lot, and you will find an astonishing variety of plants, insects, fungi, and perhaps some birds and mammals; with a lens or microscope you would discover diverse mites, nematode worms, and bacteria; and you yourself have a thriving community of many kinds of bacteria on your skin, in your mouth, and in your intestine. And this is just the beginning. From the driest deserts to the hot vents on the ocean floor, the world teems with organisms -- at least two million and perhaps more than ten million species -- that differ in the most amazing ways. They range in size from giant redwoods and whales to viruses that are hardly more than large molecules; they nourish themselves by photosynthesis, by chemical synthesis, by eating plants, dry wood, hair, live or dead animals; they are capable in some cases of living almost anywhere, and in other cases are so specialized that they can eat only one species of plant, or live within the cells of a single species of insect; they reproduce sexually or clonally, have separate sexes or not, outcross or self-fertilize; their behavior is as simple as orienting toward light, or complex enough to carry them on annual migrations between continents, or engage in complex cooperation. Among the millions of species are some without which we could not survive, and others, such as the virus that causes AIDS and the protozoan that causes malaria, that are our formidable enemies. [I-8] Our reflections raise some of the most sweeping, profound questions in biology. How do we account for the unity of life? How can we explain its astonishing diversity? What accounts for the wondrous adaptations of all species, including ourselves, as well as for their nonadaptive features? What accounts for the variation, both within and among species? [I-9] These are the fundamental questions of the science of evolutionary biology. The endeavor to answer them, and the thousand other questions that grow out of them, has spawned theories and methods that have continually deepened our understanding of the living world -- including ourselves. Every subject in the biological sciences has been enriched by an evolutionary perspective. Evolution, which provides an explanatory framework for biological phenomena ranging from genes to ecosystems, is the single unifying theory of biology. [I-10] Evolutionary science explains the unity of life by its history, whereby all species have arisen from common ancestors over the past 3 1/2 billion years. It explains the diversity and the characteristics of organisms, both adaptive and nonadaptive, by processes of genetic change, influenced by environmental circumstances. It fashions from general principles of evolution more particular explanations for the diverse characteristics of organisms, ranging from their molecular and biochemical features to their behavior and ecological attributes. In developing such explanations, moreover, evolutionary biology has honed methods and concepts that are being applied in other fields, such as linguistics, medicine, and even economics, in which changing systems are studied. Thus the perspective developed by evolutionary biology can inform the study of a wide range of phenomena. Nor does the reach of evolutionary thought stop there. Attended by controversy to be sure, the evolutionary perspective that Darwin revealed shook the foundations of philosophy, left its imprint on literature and other arts, deeply affected psychology and anthropology, and provided wholly new perspectives on what it means to be human. Probably no other discovery in science, with the exception of Newton's mechanistic, law-driven explanation of the physical world, has had so far-reaching -- and challenging -- an impact on Western thought. [I-11] This document addresses the fundamental role that evolutionary science plays in modern biology, its applications to social concerns and needs, the major future directions of evolutionary research and its applications, and the critical position that evolutionary biology must hold in biological research and in education. To address these issues, it is necessary first to describe the nature of evolutionary research and some of its accomplishments, both as basic and applied science. [II] WHAT IS EVOLUTION? [II-1] Biological (or organic) evolution consists of change (modification) in the hereditary characteristics of groups of organisms over the course of generations. Such groups of organisms, termed populations or species, are formed by division of ancestral populations or species, and the descendant groups then change independently. Hence in a long-term perspective, evolution is the descent, with modification, of different lineages from common ancestors. Thus the history of evolution has two major components: branching of lineages and change within lineages. Successive changes in the characteristics of diverging lineages result in initially similar species that become ever more different, so that, over the course of sufficient time, they may come to differ profoundly. [II-2] The hierarchically organized patterns of commonality among species -- such as the common features of all primates, all mammals, all vertebrates, all eukaryotes, and all living things -- reflect a history in which all living species can be traced back through time to fewer and fewer common ancestors, and ultimately to one ancestor of all. It is profoundly wonderful that all forms of life, from viruses to redwoods to humans, are literally related by unbroken chains of physical descent. Much of this history can be described by the metaphor of the phylogenetic tree (Figure 1). Although not all of this history is recorded in the fossil record by any means, much of it is. The fossil record documents simple, bacteria-like life as far back as 3.5 billion years, as well as a subsequent history of diversification, origination of major new groups of organisms ("higher taxa" such as orders and classes), and extinctions. The evidence for descent from common ancestors, however, lies not only in the fossil record, but also in the common characteristics of living organisms, including their anatomy, embryological development, and DNA. On such grounds, for example, humans and apes clearly had a relatively recent common ancestor; a more remote common ancestor gave rise to all primates; and successively more remote ancestors gave rise to all mammals, to all tetrapod (four-legged) vertebrates, and to all vertebrates, including fishes. [II-3] "Evolutionary theory" refers to a body of statements about the processes of evolution that are believed to have caused the history of evolutionary events. (As noted later, "evolutionary theory" does not refer to the proposition that evolution has occurred.) These processes include both random (stochastic) and nonrandom (deterministic) factors. "Random" or "chance" events are those that cannot be predicted by knowledge of a specific factor, or perhaps by any known factors. (For example, knowing the sex of a couple's children does not predict the sex of their next child.) However, it is often possible to state the probability (the "chance") of one versus another outcome (such as the probability that the next child will be a daughter). In contrast, if we can at least sometimes predict events from knowledge of other factors, then the process is nonrandom. (We can predict at least the direction of difference in accident rates among groups of people from data on their driving habits.) Both random and nonrandom factors may act at the same time (even the best driver may experience an accident due to various unpredictable events). "Random," incidentally, is not a synonym for "purposeless." The orbit of the earth is predictable (nonrandom), but it lacks purpose. In none of the natural sciences does the concept of purpose play any role. ---------------------------------------------------------------------------------------------------------- BOXED MATERIAL TO GO NEAR HERE: SOME IMPORTANT VOCABULARY Gene: A unit of heredity, usually a sequence of DNA that encodes a protein or other product that influences the development of one or more characteristics. Each amino acid in a protein chain is encoded by one or more specific triplets of four kinds of nucleotide bases. The term locus, meaning the site on a chromosome occupied by a gene, often refers to the gene itself. Allele: One of several alternative forms of a gene, differing in nucleotide sequence, and usually differing in their effect on some characteristic. Genotype: A specific combination of alleles at one or more loci. Organisms such as humans carry two gene copies at each of most loci; their genotype at a given locus is homozygous if the two copies are the same allele, and heterozygous if they are different alleles. Phenotype: An observable characteristic(s) of an organism, e.g., eye color, respiration rate, number of offspring produced. Both genetic and environmental factors often determine the phenotype. Often, a given phenotype can be due to any of several different genotypes, and conversely, a given genotype can have different phenotypes, depending on environmental effects. Character: A specific feature, e.g. "molar teeth." A character state is one of several alternative conditions, e.g. the specific number of molars. A quantitative character varies continuously (e.g., weight) rather than discretely, usually because of the effects of both environment and the action of several or many genes, hence the term "polygenic" character. Pleiotropy: The effects of different alleles of a single gene on more than one characteristic. Development: The changes that an individual organism undergoes during its lifetime, from egg through maturity to death. "Ontogeny" is approximately synonymous. Mutation: Alteration of the DNA sequence of a gene, hence the origin of a different allele. Population: A local group of individuals of a species; in sexually reproducing organisms, members of a population interbreed more frequently than with members of other populations. Allele frequency: The proportion of gene copies in a population that are a specific allele. If the population has N individuals, each with 2 gene copies, the total number of genes is 2N. Fixation: An allele reaches fixation if it replaces all other alleles in a population, so that its frequency is 1 (i.e., 100%). Polymorphism: Presence in a population of two or more alleles, so that no one of them is fixed. Selection: Shorthand for "natural selection," i. e., consistent differences in the rate of survival or reproduction between different genotypes or alleles, due to differences in their phenotypes. Fitness: The rate of increase in number, per generation, of a genotype or allele, relative to other genotypes, due to its average rate of survival and reproduction. Neutral alleles: Two or more alleles that do not differ in their average effect on fitness. They are said to be "selectively neutral." Genetic drift: Random changes in the frequencies of alleles within a population, often because they are selectively neutral or nearly so. Gene flow: The incorporation of genes from one population into another (usually of the same species), due to movement of individuals or their gametes such as pollen, followed by interbreeding. Species: A group of populations that actually or potentially exchange genes by interbreeding, and which are reproductively isolated from other such groups by biological differences that reduce or prevent gene exchange. Speciation is the origin of two or more species by division of an ancestral species into reproductively isolated populations. Taxon: A named entity in biological classification, such as a species ( e.g., Homo sapiens) or an order (e.g., Primates). Higher taxa are those above the species level (e.g., genera, families, orders), and ideally are monophyletic groups, i.e., sets of species that have descended from a common ancestor. ---------------------------------------- END BOXED MATERIAL -------------------------------- [II-4] Biological evolution is believed to occur as the consequence of several fundamental processes. [II-5] 1. The variation in the characteristics of organisms in a population arises originally by random mutation of the DNA, the genes that affect the development of the characteristics. ("Random" here means that the mutations occur irrespective of their possible consequences for survival or reproduction.) The variants of a gene that arise by mutation are called alleles. random mutation has been extensively studied, especially in laboratory stocks of organisms such as bacteria and fruit flies (Drosophila). [II-6] 2. This genetic variation is often augmented by recombination , the formation of various combinations of alleles at different gene loci. This process is especially important in sexually reproducing organisms. Variation is also augmented by gene flow, or input of variant genes from other populations of the species. [II-7] Evolutionary changes within the population are then changes in the proportions of different genes that affect various characteristics. With some exceptions, changes transpire independently in different genes or characteristics. However, changes at several gene loci may occur if they all affect the same characteristic, and conversely, change at a single locus can affect more than one feature, by influencing the complex, interrelated processes of development. [II-8] Changes in the proportion of alleles at each locus can be due to two major processes of sorting, whereby some individuals leave more descendants than others, and therefore bequeath more genes to subsequent generations. One sorting process, random genetic drift, consists of random variation in survival and reproduction; the other, natural selection, consists of nonrandom differences. [II-9] In random genetic drift, different genotypes vary at random in their rates of survival or reproduction. Hence the frequencies of alleles fluctuate by pure chance. Eventually, one allele will replace others (i.e., be fixed in the population). Genetic drift is most important when the alleles are selectively neutral (i.e., the variants do not substantially differ with respect to survival or reproduction), and it proceeds faster, the smaller the population is. Genetic drift is change but not adaptation. [II-10] The other sorting process is natural selection, which is a name for any consistent (that is, biased, nonrandom) differences in the rate of survival or reproduction between variant genes or genotypes. In some cases, one variant survives or reproduces better than others (has higher fitness) almost irrespective of environmental conditions, but in most cases environmental circumstances affect which variant has the higher rate of survival and reproduction. The relevant environmental circumstances depend greatly on an organisms' way of life -- much that is relevant to a squirrel is irrelevant to an earthworm or mushroom -- and they include not only physical factors such as temperature, but also other species, as well as other members of the organism's own species, with which it competes, mates, or has other social interactions. A common consequence of natural selection is the process of adaptation, an improvement in the average ability of the population's members to survive and reproduce in their environment. (The word "adaptation" is also used for a feature that has evolved as a consequence of natural selection.) Natural selection tends to eliminate genes and characteristics that reduce fitness (such as mutations that cause severe birth defects in humans and other species), and it also acts as a sorting device -- a sieve -- that preserves and increases the abundance of combinations of genes and characteristics which would occur only rarely by chance alone. Thus selection plays a "creative" role, by making the improbable more probable. Often the effect of selection will be to completely replace formerly common genes and characteristics by new ones (directional selection), but under some circumstances, "balancing selection" can maintain several genetic variants indefinitely in a population (a state of genetic polymorphism, such as sickle-cell and "normal" hemoglobins in some human populations in Africa). [II-11] Natural selection is the cause of adaptations such as eyes, hormonal controls on development, and courtship behaviors that attract mates. Because it is a purely statistical difference in survival and reproduction, from one generation to the next, natural selection cannot have any foresight, cannot have a goal, and therefore cannot prepare a species for future contingencies. Because the features that are adaptive for any species depend on the species' local environment and way of life, natural selection need not generate anything that we might call "progress" in the long term. [II-12] 6. If individuals move among populations of a species and interbreed (i.e., if there is gene flow), new genes and characteristics may spread from their population of origin throughout the species as a whole. [II-13] 7. Over a long enough time, new mutations and recombinations, sorted by genetic drift or natural selection, can alter many characteristics and can alter each characteristic both quantitatively and qualitatively. The result can be indefinitely great change, so that a descendant species differs strikingly from its remote ancestor. [II-14] 8. If gene flow among different, geographically separated populations of a species is slight, different genetic changes can transpire. Because the populations experience different histories of mutation, genetic drift, and natural selection (the latter especially if environments differ), they follow different paths of change, diverging in genetic constitution and in the organisms' characteristics (geographic variation). The differences that accumulate eventually cause the members of different populations, if they should encounter each other (by expanding into new areas), to be reproductively isolated: they do not exchange genes because they do not mate with each other, or if they do, the "hybrid" offspring are inviable or infertile. By anyone's definition of the term, they are then different species. The profound significance of their becoming different reproductively isolated species is that they are likely to evolve independently from then on, and to give rise to yet other species, which ultimately may become exceedingly different from each other. Speciation, the process of becoming different species, is the fundamental process of branching that gives rise to the phylogenetic tree of living things. Successive speciation events, coupled with divergence, gives rise to clusters of "twigs" on the phylogenetic tree, each cluster perhaps being named as a higher taxon (genus, family, etc.). [II-15] 9. Entities that vary, replicate, and show common ancestry can be identified at several levels: genes, organisms within populations, populations within species, species, higher taxa. Sorting processes can occur at any of these levels; that is, random or nonrandom differences in rates of survival or origination (reproduction in a broad sense) can occur among any of these entities. Thus, variant genes might spread irrespective of their effects on organisms' survival or reproduction; the complexion of a species might be altered by differences in the rate of extinction or proliferation of whole populations that differ in some feature; and the changing history of biological diversity on earth has been influenced by differences among species and higher taxa in rates of extinction (e.g., mammals and birds replacing dinosaurs) and origination (e.g., higher speciation rates of rodents than anteaters). [II-16] Although each of the separate processes involved in evolution seems relatively simple, evolution is not as straightforward as this summary might make it appear. The various factors of evolution interact in complex ways, and each of them itself has many nuances and complexities. Thus when one gene affects several characters, when many genes affect one character, when variation in a character is affected by interactions between genes and environment, when selection changes from year to year, or when conflicting selection pressures affect a characteristic (e.g., when selection by mates to make a male conspicuous is opposed by selection by predators against conspicuousness): when such complexities are taken into account, it can be quite difficult to predict when and how a characteristic will evolve. Mathematical or computer simulation models are then invaluable tools for understanding how evolution of a feature is likely to proceed. A great deal of evolutionary research consists of formulating such models, and then testing them by experiment or observation. [III] EVOLUTION AS FACT AND AS THEORY [III-1] It is important to distinguish between the history of evolution and the processes held to explain this history. Most biologists regard the history of evolution -- the proposition that all species have descended, with modification, from common ancestors -- as a fact, that is, a claim supported by such overwhelming evidence that it is accepted as true. The body of principles that describe the causal processes of evolution, such as mutation, genetic drift, and natural selection, is the theory of evolution. "Theory" is used here as it is used throughout science, as in "quantum theory" or "atomic theory," to mean not mere speculation, but a well-established system or body of statements that explain a group of phenomena. Although most of the details of the history of evolution remain to be described (as is true also of human history), the statement that there has been a history of common ancestry and modification is as fully confirmed a fact as any in biology. In contrast, the theory of evolutionary processes, like all scientific theories, continues to evolve, as new information and ideas deepen our understanding. Evolutionary biologists have great confidence that the major causes of evolution have been identified, but there is some disagreement on the relative importance of some evolutionary factors, many processes are insufficiently understood, and new information continues to add detail and to modify our understanding. [III-2] To claim evolution as a fact is to confront controversy, for probably no claim in all of science evokes as much emotional opposition as evolution. The appendix on "Evolution: Fact, Theory, and Controversy" discusses this issue. [IV] WHAT IS EVOLUTIONARY BIOLOGY? [ALTERNATIVE: THE STRUCTURE OF EVOLUTIONARY BIOLOGY] [IV-1] Evolutionary biology is the discipline that (1) describes the history of life and (2) analyzes the processes that account for this history. It seeks to explain the diversity of life: the variety of organisms and their characteristics, and their changes over time. Thus evolutionary biology is one of the "biodiversity sciences," overlapping with other biodiversity sciences such as systematics, which describes and classifies biological diversity, and ecology, which analyzes the abundance and distribution of species and their interactions with one another and with their environment. [IV-2] Evolutionary biology has two encompassing goals, from which spring numerous other aims that are the objectives of most day-to-day research. The two great goals are [IV-3] 1. To discover the history of life on earth. That is, (1) to determine the ancestor-descendant relationships among all species that have ever lived -- their genealogy, or phylogeny; (2) to determine the times at which they originated and (in most cases) became extinct; and (3) to determine the origin and the rate and course of change in their characteristics. [IV-4] 2. To understand the causal processes of evolution. Referring back to the earlier sketch of evolutionary theory, we see the need to understand how and what kinds of hereditary variations originate; how the various sorting processes, at every level from sorting of genes to sorting of higher taxa, act to affect the fate of variations; how populations become different species; what the relative importance is of the many coacting processes of change; how rapidly changes transpire; and how factors such as mutation, natural selection, and genetic drift have given rise to the diverse molecular, anatomical, behavioral, and other characteristics of different organisms. Virtually all of biology bears on this vast project of understanding the causes of evolution, and reciprocally, understanding the processes of evolution informs each area of biology in mutual dialogue. (To be sure, the dialogue is more active with some biological disciplines than others, but it is being actively developed in areas such as medicine and neurobiology.) [IV-A] Subdisciplines of evolutionary biology [IV-A1] Evolutionary biology consists of numerous subdisciplines that differ in their subject matter, questions, and methods. Some contribute more to analyzing the history of evolution, and others more to analyzing processes of evolutionary change, but advances toward each of these goals contributes to advances in the other. Some of the major subdisciplines are: [IV-A2] 1. Evolutionary systematics. Systematists distinguish and name species, infer evolutionary (phylogenetic) relationships among species, and classify species into higher taxa on the basis of their evolutionary relationships. Thus, much of systematics is inseparable from the study of evolution. Because distinguishing species requires analyzing variation within and among populations, systematists have contributed greatly to our understanding of variation and the nature of species. Determining phylogenetic relationships, which has become one of the most active and successful areas of evolutionary biology, consists of determining the history of common ancestry among organisms, and can shed much light on the stages by which their characteristics evolved. (For example, by studying phylogenetic relationships among living species, it is evident that humans evolved from an ancestor that walked on all four limbs and had a smaller brain and larger canine teeth than we do. It is also clear that the eight different hemoglobin genes in the human genome evolved, over the course of vertebrate history, by successive duplications of a single ancestral gene, as found today in primitive "fishes" such as lampreys.) The analytical methods that have been developed to trace phylogenetic relationships among species are also used to determine the genealogical relationships among alleles of a gene within species, that differ in DNA sequence. [IV-A3] To describe fully the history of life requires experts on the living and extinct members of groups of organisms -- plants, bacteria, snails, dinosaurs, mammals, and many others. These experts, many of whom are systematists, may call themselves botanists, entomologists, microbiologists, and the like. Their special knowledge is indispensable both for inferring the history of evolution and, often, for understanding the detailed workings of evolutionary processes. Mammals, insects, plants, and bacteria differ so profoundly that generalized processes such as natural selection and speciation operate differently, operate on different features and on different time scales, and have different consequences. Moreover, each such group of organisms presents special, fascinating and often important questions: How does the warm-blooded condition in mammals affect the evolution of body size? Why have many insects become so specialized that they feed on only one species of plant? How does the peculiar and apparently rare exchange of genes in parasitic bacteria affect their ability to adapt to their host's defenses -- and to antibiotics? [IV-A4] Knowledge of relationships among species, which may be reflected in their classification, is useful because of its predictive value. Closely related species generally have more similar characteristics than distantly related species. Thus, for example, plants related to a species in which a pharmacologically useful compound has been found are likely to contain similar compounds, which might be even more useful. [CAN ANYONE CITE AN EXAMPLE OF THIS?] Systematists' special knowledge of particular groups of organisms often has unexpected uses. For instance, entomologists are often called on to identify novel pest insects, the first step toward controlling them. Mammalogists' knowledge of the systematics and biological characteristics of deer mice unexpectedly became invaluable when the novel hantavirus, harbored by these mice, emerged in the southwestern United States. [IV-A5] 2. Evolutionary paleontology. This field, often called paleobiology, addresses the large-scale evolutionary patterns of the fossil record, including the origins and fates of lineages and major groups, evolutionary trends and other changes in morphology (anatomy) through time, and geographic and temporal variations in diversity through the geologic past. It also seeks to understand the physical and biological processes and the unique historical events that have shaped evolution. It asks, for example, how the biologically-mediated buildup of oxygen in the earth's atmosphere and oceans between 2.5 and 0.5 billion years ago influenced microbial evolution and the eventual appearance of multicellular organisms; what the causes were of the apparently explosive diversification of animal phyla about 545 million years ago; and how the catastrophic extinction of dinosaurs and other dominant animals 65 million years ago influenced the subsequent evolution of modern forms of life. Paleontological data provide a window on deep time, and thus permit the direct study of problems ranging from the rate of change in the form and distribution and distribution of species over millions of years, to the evolutionary responses of major groups such as dinosaurs, insects, or reef-building corals to both catastrophic and more gradual environmental changes. Although systematic studies of living organisms enable us to infer the past existence and some of the characteristics of organisms long since extinct, the fossil record provides the only direct evidence on extinct forms of life. Moreover, it provides insights into evolutionary processes that cannot be studied in living organisms, such as the evolutionary consequences of differences among taxa in rates of speciation and extinction. Paleontology is intimately related to systematics (since analyses of the fossil record depend on the phylogenetic relationships and classification of fossilized organisms), to geology (which provides bases for determining the ages of fossils and ancient environments), and studies of the functional morphology and ecology of living organisms (which provide bases for interpreting the characteristics of extinct species). [IV-A6] 3. Evolutionary genetics. Evolutionary genetics (including population genetics) is a central discipline in the study of evolutionary processes. It uses both molecular and classical genetic methods to understand the origin of variation by mutation and recombination, describes patterns of genetic variation within and among populations and species, and employs both empirical study and some of the most advanced mathematical theory in biology to describe how this variation will be affected by processes such as genetic drift, gene flow, and the many forms of natural selection. The mathematical theory of evolutionary genetics is essential for interpreting genetic variation and for predicting evolutionary changes when many factors interact. It also provides a strong foundation for understanding the evolution of special classes of characteristics, such as genome structure and life histories. Empirical studies in evolutionary genetics test these theories, describe patterns of genetic variation within species, determine the causes of this variation, document the many ways in which natural selection operates, and characterize the genetic differences between species. [IV-A7] 4. Evolutionary developmental biology. This field, newly invigorated by advances in the understanding of developmental mechanisms, seeks to describe evolutionary changes in the processes that translate an organism's genetic information (in DNA) into the organism's phenotype (its anatomical and other characteristics). In part, it aims to describe how variation at the genetic level results in variation in the organismal characteristics that affect survival and reproduction. Perhaps its greatest significance lies in its potential to reveal the extent to which developmental processes bias, constrain, or facilitate the evolution of the phenotype. [IV-A8] Several areas of evolutionary biology are devoted to refining the general principles of evolutionary theory in order to understand particular classes of characteristics. Each of these fields lies at the interface between evolutionary biology and one or more disciplines that do not explicitly take evolution as their subject. The consequent interchange can enrich both these fields and evolutionary biology. [IV-A8] 5. Molecular evolution. Developing hand in hand with the spectacular advance of molecular biology, this field describes the history and causes of evolutionary changes in the nucleotide sequences of genes, the structure and number of genes, and their physical organization on chromosomes. It also addresses questions such as the evolutionary effects of transposable elements (movable genes) and the significance of the huge amount of apparently informationless, "nonfunctional" DNA in most species' genomes. This field also provides molecular tools for investigating a vast number of questions about the evolution of organisms as such, ranging from phylogenetic relationships among species to mating patterns within populations. [IV-A9] 6. Evolutionary physiology and morphology. This broad field studies how the biochemical, physiological, and anatomical features of organisms provide adaptation to their environments and ways of life, as well as the history of these adaptations. Equally important, it is beginning to define the limits to adaptation -- for such limits may restrict a species' distribution or lead to its extinction. Among the other questions studied in this field are, "How do the form and function of a feature change in relation to each other during evolution?" "How and why are some species tolerant of a broad range, and others of only a narrow range, of variation in environmental factors such as temperature?" [IV-A10] 7. Evolutionary ecology. This field asks how the life histories, diets, and other ecological features of species evolve, how species evolve in response to each other, and how these processes affect the composition and properties of assemblages of species (communities and the ecosystems of which they are part). Salient questions include: How do we account for the evolution of short or long life spans, of high or low reproductive rates, and of rapid or slow maturation in different species? Why are some species broadly and others narrowly distributed? How do competing species, and predators and prey, affect each other's evolution, and does this evolution lead to stable coexistence or to extinction? Do parasites (including microbial pathogens) evolve to be more benign or more virulent as time passes? How do evolutionary changes and evolutionary history affect the number of species in a community, such as a tropical forest compared to a boreal forest? [IV-A11] 8. Behavioral evolution, also called behavioral ecology. Behavioral characteristics evolve in much the same way as structural features, and similarities among species may be due to descent from a common ancestor or to similar selective pressures acting in different lineages. Behavioral evolutionists study the evolution of adaptations such as mating systems, courtship behavior, foraging behavior, predator-escape mechanisms, and cooperation. In order for behavior to evolve, there must be change in its underlying neural, hormonal, and developmental mechanisms. These too are objects of evolutionary study, as are the adaptive differences among species in memory, patterns of learning (when, what, and for how long), and other cognitive processes, some of which are reflected in differences in brain structure among species. Behavior, physiology, structure, and life history patterns often evolve in concert, and often evolve considerable flexibility in response to varying environmental conditions. What is more controversial is the extent to which the patterns found in other species can be applied to human behavior. [IV-A12] Human evolution. Many evolutionary biologists draw on several or many of the conceptual subdisciplines of evolutionary biology to study particular groups of organisms. Of these, one is especially notable: the genus Homo. The many anthropologists and biologists who take human evolution as their subject use principles, concepts, methods, and information from evolutionary systematics, paleontology, genetics, ecology, behavior -- the full panoply of evolutionary disciplines. Some researchers work on the evolutionary history of humans, drawing on paleontology, molecular systematics and population genetics, and to some extent on archaeology; others study genetic variation and the processes that affect it in contemporary human populations (a subject intimately related to other areas of human genetics, such as medical genetics); still others work in the controversial area of human behavior and psychology. In some ways, the evolutionary genetics and history of humans is better understood than for almost any other species. [IV-B] Perspectives from Evolutionary Biology [IV-B1] The biological sciences can be roughly divided into "functional biology" and "historical biology." [CITE MAYR] Functional sciences such as molecular biology and physiology ask "how" questions: how organisms and their constituent parts work. Evolutionary biology, a largely historical science, adds "why" questions: why do specific organisms have particular features rather than others? The major answers to such questions are "because this species inherited the future from distant ancestors" and "because a history of natural selection favored this feature over others in the recent past." That a human embryo has gill slits can be understood only by inheritance from early vertebrate ancestors; that we walk upright can be understood as an adaptation, a trait favored by natural selection in our more recent ancestors. In emphasizing history, we must, at the same time, recognize that evolution is an active, ongoing process. Nevertheless, the historical perspective complements the descriptions of function provided by other disciplines. Only by this approach can we fully understand why some viruses, but not others, cause disease, or why humans have a life span longer than rats' but shorter than tortoises'. [IV-B2] The study of evolution entails several perspectives that are important conceptual contributions to biology. [IV-B3] -- Chance and necessity. In a book bearing this title, Francois Jacob, who shared a Nobel Prize for discovering mechanisms by which the activity of genes is regulated, reflected on a fundamental principle of evolutionary science: that living systems owe their properties to an interplay between both stochastic (random) events and deterministic (consistent, predictable) causes. A fully predictive, deterministic theory of biology is almost surely unattainable because of the role of chance, such as the randomness of mutations and the asteroid impacts and other historical accidents that have influenced the course of species' evolution. Evolutionary biologists have developed probabilistic theories that describe the probability of various evolutionary trajectories, but biologists cannot specify in precise detail how any single characteristic will evolve over long periods of time, because of the ineradicable randomness of events such as mutation and changes in the environment. [IV-B4] An important corollary of random events is historical contingency. Although some adaptations to environmental factors are reasonably predictable, other characteristics of organisms are the consequence of "historical accidents" that launched evolution along one path rather than others. For example, the modifications of the forelimbs for flight are very different, but nonetheless effective, in birds, bats, and pterodactyls, presumably because different mutations presented natural selection with different options in these lineages. As Robert Frost wrote, "Two roads diverged in a wood, and I -- / I took the one less traveled by, / And that has made all the difference." [IV-B5] -- Variation. Whereas physiologists may view variation in, say, rats' respiratory rates as undesirable "noise" or experimental error that obscures the "true" value, variation is the all-important object of study for most evolutionary biologists. Probably no lesson from evolutionary biology is more important than the realization that there are no Platonic "essences," or fixed, "true," "normal" properties. Every characteristic of a biological system can vary and change. Thus the norm, or average, is an abstraction that gives way to the reality of variation, both within and among species. Evolutionary biologists' obsession with variation has borne methodological fruit, namely some of the statistical methods for analyzing variation that are widely used outside our field. (For example, one of the pioneers of population genetics, R. A. Fisher, developed the Analysis of Variance, and other evolutionary biologists have contributed to developing methods of cluster analysis, path analysis, and maximum likelihood.) The evolutionary perspective on variation has implications for how we think about "normality" and "abnormality", and about differences in human characteristics. Awareness of variation within populations is a powerful antidote to racism and stereotyping of ethnic and other groups. [IV-B6] -- Biological diversity. Evolutionary biologists are not only intrigued by the diversity of life, but also are keenly conscious of the contributions to biology that come from studying diverse organisms. Immense advances in biology have come from in-depth study of "model organisms" such as yeast, corn, rat, the bacterium Escherichia coli, and the fruitfly Drosophila melanogaster; indeed, many evolutionary biologists study these model organisms. However, without examining other species, we cannot know how widely applicable the principles revealed in model systems are -- and, in fact, we know that many such principles apply only with modification, or not at all, to vast numbers of other species. Gene regulation, first elucidated in E. coli, is very different in bacteria than in eukaryotes, and none of the model organisms can teach us about physiological adaptations to water shortage in desert plants (including potential crops), the mechanisms by which parasites combat their hosts' immune systems, or the evolution of social behavior, communication, or learning in animals such as primates. Different organisms present different biological questions, and some species are more suitable than others for addressing each question in biology. Evolutionary biologists and other biodiversity scientists are the carriers of knowledge about the diversity of organisms, and provide indispensable guidance for advances throughout biology and its applications. It is from this fount of knowledge, for example, that bacteria in hot springs were identified as a possible source of a heat-adapted DNA polymerase enzyme that is now the key ingredient in the polymerase chain reaction (PCR), the technological breakthrough that has revolutionized molecular biology and made possible genetic engineering. There is no way to predict when or where such knowledge of biodiversity will be useful. [SIDEBAR #2 on applications of biodiversity knowledge?] [V] HOW EVOLUTION IS STUDIED [V-1] Because evolutionary biology embraces everything from molecular to paleontological studies, a catalogue of methods would fill several volumes. We can note only a few of the most general, commonly used methods, emphasizing those used more in evolutionary biology than in other branches of biology. [V-2] 1. Phylogenetic inference methods are used to estimate genealogical relationships among species (living and extinct). Major recent advances in logical and computational methods, developed by systematists and population geneticists, have greatly enhanced the confidence with which we can estimate phylogenetic relationships. Greatly oversimplified, the major principle is that species which share the greatest number of derived ("advanced") features stem from a more recent common ancestor than species that share fewer. It is obvious, then, that rats, apes, and other mammals share a more recent common ancestor with each other than with birds or lizards, since the mammals possess many unique, derived features (e.g., milk, hair, single lower jawbone). It is less obvious, but equally demonstrable, that vertebrates are more closely related to echinoderms (starfishes and relatives) than to almost any other phylum of animals; and it is certainly not obvious, but nonetheless increasingly likely as new data accumulate, that chimpanzees are more closely related to humans than to gorillas. [FIGURE?] These conclusions are based not only on improved analytical methods, but also on a virtually inexhaustible treasure trove of new data: DNA sequences that reveal far more similarities and differences among species than can be found in their anatomy. [V-3] The same methods used to infer the genealogy of species are used to infer the genealogy of the genes themselves. Thus, molecular evolutionary studies can use DNA sequences to estimate how recently variants of a gene carried by different people arose from a single ancestral gene, relative to other variants. [SIDEBAR #3 on mitochondrial Eve and out-of-Africa?] These methods have also shown that the single hemoglobin gene of primitive vertebrates has been extensively duplicated within the genome of later vertebrates, giving rise to the eight different hemoglobin genes in humans, which play different functional roles in the embryonic, fetal, and adult stages. [V-4] 2. Paleontological databases. Evolutionary paleontology is founded on systematics, including phylogenetic inference, for it is necessary to classify and determine the relationships of fossilized organisms before anything else can be done with them. Once this is done (and it may not be easy), fossils are used for two major kinds of evolutionary study. One is tracing evolutionary changes in the characteristics of lineages through geological time, such as the evolution of the horse family or the descent of mammals from reptilian ancestors. The other is tracing the times of origination and extinction of lineages, and thus changes in biological diversity -- and relating such changes to continental drift, climate, and other events in earth history. For instance, each of five great "mass extinctions" -- one of them perhaps due in part to an asteroid impact -- was followed by a great increase in the rate of origin of species and higher taxa, providing evidence that diversification of species is stimulated by availability of vacated resources. [FIGURE?] Such studies rely on analyzing computerized databases of the geological and geographic occurrence of thousands of fossil taxa, data accumulated by hundreds of paleontologists throughout the world over the course of two centuries. [V-5] 3. Characterizing genetic and phenotypic variation. Because of the pivotal role of variation in evolutionary theory, characterizing variation is one of evolutionary biology's most important tasks. The statistical methods used are applied to data of many different kinds. Quantitative genetics, which is also used extensively in breeding crops and domestic animals, is an important tool for measuring and distinguishing between genetic and nongenetic variation in anatomical and other phenotypic characteristics. One method of making this distinction is to grow samples of different families or populations in the same environment, a technique pioneered by students of plant evolution who thereby showed that both genetic and environmental factors underlie the phenotypic differences among populations of a species. Another method is to measure similarities among relatives, which may require that relationships be determined within natural populations. Molecular genetic markers often provide such knowledge. [V-6] 4. Inference from genetic patterns. Many evolutionary changes (though not all) take immense amounts of time, so the processes involved are often inferred from patterns rather than observed directly. Many hypotheses about evolutionary processes are tested by comparing patterns of genetic and phenotypic variation with those predicted by evolutionary models, such as mathematical models of natural selection and genetic drift. For instance, the "neutral theory" of molecular evolution by genetic drift holds that molecular variation within species should be greater, and divergence among species more rapid, for genes in which most mutations have no effect on organisms' fitness than for those in which most have a strong effect. Under this model, genes encoding proteins with weakly constrained function, and DNA that does not encode functional proteins at all, should display more nucleotide variation within and among species than genes which encode functionally important proteins. Studies of DNA variation have abundantly confirmed this model; for instance, noncoding DNA is far more variable than coding sequences. This principle is so powerful that molecular biologists can now routinely use the level of sequence difference among species as a clue to whether or not a newly described DNA sequence has an important function. [V-7] 5. Observing evolutionary change. Although necessarily smaller in magnitude than the evolution of new higher taxa (which requires thousands or millions of years), some important evolutionary changes happen fast enough to document within one or a few scientific lifetimes. This is especially true when, due to human activities or other causes, a population's environment changes, or a species becomes introduced into a new region. Changes in food supply due to drought in the Galapagos Islands caused substantial, although temporary, evolutionary change in the beak size of a finch, within just a few years [GRANT, Weiner]; a virus introduced to control rabbits in Australia evolved to be less virulent in less than a decade (and the rabbit population evidently became more resistant); rats have evolved resistance to the poison warfarin; hundreds of species of crop-infesting and disease-carrying insects have evolved resistance to DDT and other insecticides since World War II; and the rapid evolution of antibiotic resistance in pathogenic bacteria, viruses, and protozoa poses one of the most serious problems in public health. [SIDEBAR #4 on EVOL of RESISTANCE] Some such evolutionary changes are documented by measuring samples successively during an investigator's lifetime; some changes in morphology are documented by comparing contemporary organisms with century-old museum specimens. [V-8] 6. Experiments. Evolutionary science employs many kinds of controlled experiments. Among the most common are those that analyze evolutionary change in experimental populations, sometimes in nature, and often in the laboratory, using organisms with short generation times that can evolve rapidly. For example, experimenters have used laboratory populations of bacteria to monitor the course of adaptation to high temperatures, novel chemical diets, antibiotics, and bacteriophage (viruses that attack bacteria), and have characterized the new mutations underlying these adaptations. One group of researchers predicted the evolutionary changes in life history characteristics (e.g., rate of maturation) that guppies should evolve if they were to be subjected to a certain species of predatory fish. They introduced guppies into a Trinidad stream where this predator occurred, and found that after about six years, the introduced population differed from the ancestral population just as they had predicted. [V-9] 7. The comparative method. Convergent evolution is the independent evolution, in different lineages, of similar characteristics that serve the same or similar functions. For example, several unrelated groups of fishes that inhabit turbid water have independently evolved the capacity to generate a weak electric field that enables them to perceive nearby objects. (These fishes also use it to communicate, and a few species, such as the electric eel , stun prey electrically.) Convergent evolution is so pervasive that it can often be used to test hypotheses. If we hypothesize a certain function for a feature, then its occurrence or condition should be correlated with specific environments or ways of life. As an example, evolutionary ecologists studying plants' defenses against herbivores predicted that irrespective of their phylogenetic relationships, plant species that inhabit environments poor in light, water, or nutrients, and which therefore cannot readily replace tissues lost to herbivores, would have greater quantities of defensive chemicals than those which occur in richer environments. By comparing many species of plants that grow in different environments, evolutionary ecologists have found considerable evidence supporting this prediction. [REF: Coley et al] [VI] SOME ACCOMPLISHMENTS OF EVOLUTIONARY BIOLOGY TO DATE [VI-1] Scarcely any feature of biological systems, characteristic of organisms, or major group of organisms has failed to inspire at least some evolutionary research, so a full list of accomplishments -- spectacular in some cases and modest in others -- would be very long. Here is a capsule description of some of the most important ones. [VI-2] 1. Many lines of evidence unequivocally demonstrate that evolution has occurred -- that all organisms are descended from one or at most a few ancestral forms of life that existed at least 3.5 billion years ago. The staggering implication is that there has been unbroken physical, hereditary continuity from an almost unimaginably ancient ancestor to every human, fly, plant, and bacterium that lives today, and that all these organisms are literally related by bonds of common descent. The traditional evidence for the relatedness of all life was commonalties in phenotypic features such as cell structure and the universal use of L rather than R optical isomers of the amino acids that compose proteins. To these commonalities, we can now add the universal use of nucleic acids as genetic material, the almost universal genetic code, common mechanisms of protein synthesis, and the near-identity of nucleotide sequence in many genes that play similar functional roles in very different organisms -- some of them in all organisms. For example, genes that govern the first steps in embryonic development, specifying the axes and major body regions of the embryo-to-be, are similar in sequence, organization, and basic function in insects and vertebrates; in fact, some mouse genes, implanted in a fly's genome, can "instruct" the fly genes to perform their normal developmental functions. [SIDEBAR #5 on Homeobox genes and eyeless?] Common ancestry is affirmed not only by functional genes, but also by nonfunctional DNA sequences, such as pseudogenes: "dead" genes that have lost their function, but are shared by different species, such as humans and apes. Nonfunctional morphological characteristics also attest to evolution, such as the rudimentary wings of many flightless insects that are descended from flying ancestors. [VI-3] Inferences of common ancestry based on comparisons among living organisms have been abundantly supported by direct fossil evidence of transitions, such as the evolution of flowering plants, of terrestrial amphibians from sarcopterygian fishes, of reptiles from amphibians, of birds from dinosaurs, of mammals from synapsid reptiles, and of whales from terrestrial mesonychids. [SIDEBAR or FIGURE of 1 or 2 cases] [VI-4] 2. Methods of phylogenetic, or genealogical, inference have been successfully developed. We have referred to these earlier (How Evolution is Studied). One major use of these methods is to infer relationships among species and higher taxa. This, in turn, provides a critical foundation for innumerable other studies. For instance, the history of evolutionary change in particular characteristics can be inferred from their distribution on a phylogenetic tree. We can safely say that social behavior, including a sterile worker caste, has independently evolved at least 15 times among insects, since each of 15 groups of social species, such as ants and termites, is most closely related to a different nonsocial taxon. Moreover, comparisons among closely related social insect species have shown how increasingly intricate sociality has evolved stepwise, from widely shared initial stages (facultative reproduction by workers) to later stages (distinct sterile castes) displayed by only a few "advanced" species. Phylogenetic studies have revealed or confirmed some remarkable events in the history of life. Perhaps the most stunning is that the mitochondria in eukaryotes' cells and the chloroplasts in plants are descended from bacteria that became intracellular symbionts. First proposed on the basis of ultrastructural similarities between bacteria and these organelles, the endosymbiosis hypothesis has been confirmed by sequences of mitochondrial and chloroplast DNA, which are more similar to certain bacteria than to DNA in the nucleus of eukaryotic cells. [FIGURE] [VI-5] As noted earlier, genealogical methods also yield "gene trees," portrayals of relationships among variant genes within a species and among species. When analyzed in the light of population genetic models, gene trees can reveal a great deal about the history of populations, such as their age, their former size, and their history of subdivision. (See # 12 below on human evolution.) [VI-6] 3. Documentation of the tempo and mode of evolution has been provided by both phylogenetic and paleontological studies. These show that different characteristics evolve at different rates within a lineage (mosaic evolution), so that every organism is a patchwork of characteristics that have changed substantially in the recent past, and others that have changed little for many millions of years . This is as true of DNA sequences within the genome as it is of anatomical features. Individual anatomical features and clusters of features seem usually to evolve quite rapidly at some times in the history of a lineage, and hardly at all at other times. In the fossil record, this pattern is described as "stasis" interrupted occasionally by short (less than about 100,000 years) periods of change -- a pattern that has been termed "punctuated equilibrium." (There are several competing explanations for such patterns.) Another common pattern is evolutionary (or adaptive) radiation, in which many distinct linages diverge from a common ancestor within a geologically short time. These bursts of diversification are often associated with the evolution of a novel adaptation that provides access to different resources or a new way of life (e.g., flight), or with extinction of taxa that had previously dominated the ecosystem. [VI-7] 4. Patterns of diversification and extinction have been described from the fossil record. Early diversification of fossilizable marine organisms increased to a roughly stable level for much of the Paleozoic (545-248 million years ago); diversity then dropped sharply, to perhaps 4% of previous species diversity, during the greatest mass extinction that life has yet suffered; it then rather rapidly rebounded, and has more or less increased ever since. The separation of continents during this time, creating different platforms for diversification, has contributed greatly to the global increase in diversity. Throughout this time, there has been turnover -- extinction and origination of taxa -- with diversity increasing largely due to replacement of groups with characteristically high turnover rates by groups with lower turnover rates. The several mass extinctions account for less than 10% of the total extinctions in the history of life, but they selectively extinguished certain groups, such as those with narrow geographic distributions, and they created opportunities for previously minor groups, such as mammals, to diversify. The causes of extinction, whether during mass extinctions or at other times, are poorly understood, but the biological characteristics of extinction-prone groups in the past may help to predict vulnerability to extinction among species in present-day communities. For instance, extinctions of coastal marine invertebrates during the Pleistocene ice age were more pronounced among tropical than high-latitude taxa, suggesting that tropical species are more vulnerable. [VI-8] 5. A quantitative theory of fundamental evolutionary processes has been devised and validated. The mathematical theory of population genetics -- of genetic change within and among populations -- was developed largely in the 1930's and 1940's, and has been extended and refined ever since. It describes the interplay and relative importance, under various conditions, of mutation rate, recombination, genetic drift, gene flow versus isolation, mating systems, and various forms of natural selection. The existence of each of these factors has been documented many times in both experimental and natural populations of many species, and the various factors in the models have been quantitatively estimated. Thus it is possible, for instance, to say confidently that for many phenotypic characters (e.g., morphology, behavior), natural selection is so much stronger a force than mutation that although mutation is ultimately necessary for any evolution to occur, the direction and rate of evolution will ordinarily be driven by selection. These models not only describe the conditions under which superior genotypes replace inferior ones, and how rapidly this occurs; they also predict several factors, such as certain forms of natural selection, that maintain genetic variation in populations instead of eroding it. [VI-9] With relatively little modification, the genetical theory of evolutionary processes has been extended successfully to data and processes not dreamed of in the 1930's, before the molecular basis of heredity was known. For example, fairly simple extensions of the theory predict that transposable elements -- "selfish" genes that proliferate by making copies that insert themselves throughout organisms' genomes -- would be expected to accumulate most in chromosome regions where the rate of recombination is low. Several subsequent studies of the location of transposable elements in Drosophila chromosomes supported this prediction. As another example, the neutral theory of molecular evolution, a recent extension of the theory of genetic drift developed by Sewall Wright in the 1930's, predicts that nucleotide differences should be greatest in those parts of a gene that code for regions of the protein that are not functionally critical. In one of many confirmations of the theory, site-directed mutagenesis was used to create mutations in various parts of the gene encoding alkaline phosphatase in the bacterium E. coli. As predicted, mutations in those regions that differ little in nucleotide sequence among species of bacteria proved, in the experiment, to impair function, and they reduced the growth rate of the bacteria. Mutations in regions that vary widely among species had much less of an impact. [REF duBose et al] [VI-10] 6. Populations are now known to be highly variable genetically. Several decades of study of many species, using both classical and molecular techniques, have revealed extensive genetic variation within and among populations in almost all cases. Molecular methods of assessing variation, including protein electrophoresis and DNA sequencing, have achieved great prominence, and have revealed that almost all populations of organisms, including humans, harbor immense amounts of genetic variation. Certainly no two humans that have ever lived, except for monozygotic (identical) twins, have been genetically identical. The task remains of explaining more fully why this variation exists, of determining if some features are more genetically variable than others, and of finding out how readily natural selection can shape this variation into new adaptations to various environmental challenges. [VI-11] The high levels of genetic variation have important implications. The major one is that many characteristics can evolve rapidly when environments change; the population does not have to wait for just the right mutations to occur. The reservoir of genetic variation has contributed to the success of artificial selection (conscious selection for a particular trait, by the experimenter) of desirable traits in crops and farm animals. Moreover, studies of natural selection in wild populations show that, indeed, very rapid evolution is feasible and frequent. The consequences include, for example, changes in ecological relationships among species, such as in the apple maggot fly, which only within the last century adapted to apple and is now a major pest. Methodologically, the abundant genetic variation within populations provides both opportunity to study the factors of evolution, and genetic markers for studying phenomena such as mating systems. [VI-12] 7. The process of evolution can be observed and studied. The existence of genetic variation and the continual origin of new genetic variation by mutation and recombination enable us to study many processes directly. For example, it has been shown that adaptive evolution can be based on new mutations, not preexisting variation. In one series of experiments, the evolution of a new biochemical pathway, enabling bacteria to metabolize the sugar lactose by the joint action of several enzymes and regulatory genes, has been traced . [REF Hall] Observed adaptive changes are often found to have deleterious side effects, which if sufficiently great can limit further adaptation. But subsequent genetic changes sometimes occur that remedy the side effects. For example, populations of a blowfly that attacks sheep evolved resistance to the insecticide diazinon. The resistant populations initially had slower development and physical abnormalities, but later these traits were diminished, due to selection of other genes that ameliorated the deleterious effects. [REF McKenzie] [VI-13] 8. The mechanisms by which new species arise have been clarified. The study of speciation is the analysis of how the reproductive isolation that defines populations as different species arises. Although much remains to be learned about speciation, a great deal has been learned about the genetic changes that cause this process. In animals, it appears that speciation typically involves divergence between geographically separated populations. The genes that come to predominate in one population are incompatible with genes in the other. Upon later contact between the populations, individuals of each either do not mate with the other, or if they do, they produce sterile or inviable hybrids. Genetic studies have shown that in some instances, the incompatibility is caused by a small number of genes, suggesting that speciation has occurred rapidly, while in other cases, interactions among a large number of genes cause sterility or inviability, implying that speciation has occurred slowly and gradually. Some "speciation genes" have been mapped in Drosophila and some other species, and several laboratories are now attempting to characterize such genes molecularly. There is also evidence that speciation can at least sometimes occur without geographic segregation, and that natural selection sometimes directly favors characteristics that prevent different populations from interbreeding. Certain modes of speciation are more prevalent in plants than in animals, such as speciation by polyploidy (multiplication of whole sets of chromosomes) and by recombination (whereby some genotypes of hybrids between two parent species are themselves distinct species). [SIDEBAR #5 on molecular evidence for hybrid speciation? Include something on experimentally synthesized species?] Some wild species of plants that evolved by polyploidy have been directly "recreated" in laboratory experiments. [VI-14] 9. Many different forms of natural selection have been documented. For example, selection operates not only by differences in survival and in female reproduction, but also by differences in mating success, termed sexual selection. This entails competition among males or preference by females for males with certain traits. Experiments have shown that both forms of sexual selection are responsible for many elaborate, even bizarre male behaviors and anatomical traits, such as huge antlers in deer and the plumes and bright colors of many male birds. For instance, when the long tail feathers of some male widowbirds were clipped, and the clippings glued to other males to lengthen their tails, the longer-tailed males obtained more mates, and the clipped males fewer, than control, nonmanipulated, males. [REF Andersson] Sexually selected traits often evolve even though they are positively harmful to survival, and thus do not benefit the species as a whole. In the Central American tungara frog, for example, males that include in their mating call a component that females prefer are also most likely to be attacked by a frog-eating bat. (FIGURE: photo] [VI-15] Traditionally, natural selection was defined as differences in survival or reproduction among phenotypically different individuals within populations of a species. We now know that selection can also reside in differences in survival or reproduction among genes as such (genic selection), among whole groups of individuals (group selection), and among species or higher taxa (taxon selection). Genic selection can be especially potent. Theories of "selfish genes" are based on the recognition that any variant gene that, by whatever mechanism, spreads more copies of itself through a population than other genes will replace the others. Such genes may not benefit and may even harm the organisms, and the entire species, in which they reside. Many such genes are known. They include transposable elements (described previously), which commonly cause harmful mutations and chromosome breakage, as well as "meiotic drive" genes that in a heterozygote are transmitted to more than half the gametes. (Normal segregation of two alleles in a heterozygote is 50:50). Some of these genes destroy developing sperm that lack the gene, and some can cause death or sterility of the organism. For instance, an abundant gene in mice is transmitted by more than 90% of a heterozygous male's sperm, and in homozygous condition causes death or sterility. Studies of Drosophila have shown that such "driving genes" are sometimes the target of suppressor genes, which have evolved to prevent the meiotic drive. Thus evolutionary battles among genes are common within the genome. [VI-16] Selection above the level of individual organisms also occurs, but its importance is debated. Studies of the fossil record of molluscs have shown that lineages with sedentary larvae have increased in species diversity relative to those with widely dispersing planktonic larvae, perhaps because sedentariness reduces gene exchange among populations, enabling them to become different species. Thus the "birth rate" of new species -- the rate of origination -- is greater for such lineages, and the sedentary trait becomes more prevalent in the mollusc fauna as a whole, not necessarily because it is more advantageous for individual organisms than dispersal, but because it causes proliferation of new species. [VI-17] 10. Natural selection explains the evolution of many puzzling characteristics. From a long list, we mention three: cooperative behavior, senescence, and sex. [VI-18] -- Cooperative behavior. Cooperative or "altruistic" behavior, such as helping other individuals to rear offspring, or warning them of approaching predators, seems difficult to explain, because "altruistic" genotypes divert energy that they could use for their own reproduction, or may attract the predators' attention to themselves. Thus "selfish" genotypes should have an automatic advantage over altruistic ones. How, then, can we account for the cooperative behavior of many mammals, social insects, and other animals? There are several theoretical -- and experimentally verified -- answers, chief among them the concept of kin selection, developed in the 1960's. An individual who aids others may bequeath fewer of its own genes to subsequent generations, but because relatives carry many of the same genes, it may more than compensate by enhancing the survival and replication of the genes borne by its relatives -- if it directs aid toward relatives. This is an extension of the principle that explains parental care: parents enhance their genes' prospects by taking care of offspring that carry those genes. Most cooperative behavior, it turns out on close study, is indeed directed toward related individuals, not to the species at large. Honeybees work and sacrifice themselves for their hive-mates (mostly sisters), not for members of other hives; many birds forego breeding for a year or two and help their parents rear siblings. The validity of kin selection theory has been shown in laboratory experiments and in many field studies. Flour beetles tend to be cannibalistic: they eat eggs and pupae of their own species. In experiments designed so that beetles had more access to related eggs than to those laid by randomly chosen members of the larger population, the beetles evolved a lower propensity for egg-eating within a few generations. [REF Wade] Detailed studies of bee-eaters and several other species of birds showed that compared to individuals which do not help their close relative rear offspring, young birds that do provide such aid increase the number of surviving siblings, nieces, and nephews, and thereby increase the number of copies of shared genes. [REF Koenig and Mumme] [VI-19] -- Senescence. Why, if natural selection consists in part of superior survival, do organisms undergo senescence and have a limited lifespan, shorter or longer depending on the species? The mathematical theory of life histories shows that offspring born late in a parent's life contribute less to future population numbers than offspring born earlier. (For example, if a female has 10 offspring per year, then within three years after a female's birth, a genotype that starts reproducing at one year of age could have 1000 grandchildren , but a genotype that starts reproducing at two years of age could have only 100 grandchildren.) Consequently, reproducing late in life has less "value" -- it bequeaths fewer genes -- than early reproduction. Therefore the genetic advantage of surviving to reproduce again declines with age, and natural selection against genes that reduce survival becomes weaker for genes that are expressed at later ages. Two hypotheses use this principle to explain the physiological decline that we call senescence. One holds that various deleterious mutations that are expressed only late in life accumulate in populations. Thus senescence can have different genetic causes in different individuals. The other hypothesis, based on the well-known principle that a gene generally has multiple effects (pleiotropy), holds that genes which enhance survival or reproduction early in life have deleterious side effects late in life (i. e., there is a tradeoff -- no free lunch). Both hypotheses have been supported by studies of experimental populations of Drosophila. For instance, populations propagated only from offspring born late in their parents' lifetime evolved longer lifespan, but also lower reproductive rate early in life. These experiments provided evidence for the tradeoff postulated by the pleiotropy theory of senescence. This theory, incidentally, proposes that many genes, affecting diverse physiological functions, may have such pleiotropic tradeoffs. Thus both hypotheses of the evolution of senescence predict that senescence, in humans and other species, should have multiple physiological causes, not a single, universal cause. Clarifying the evolutionary and physiological causes of senescence is clearly an important goal for future research. [VI-20] -- Sex. Possibly no biological phenomenon is as puzzling, in an evolutionary framework, as sex. It is not necessary for reproduction -- bacteria and diverse fungi, plants, and animals commonly do without it -- and it is a risky, time-consuming affair in which many individuals do not succeed. Even worse, the rate of growth in numbers of a sexual genotype is usually only about half that of an asexual genotype, since about half the population - the males -- do not add to the number of offspring produced. Why, then, is sex so prevalent among species? One possible answer is that the lack of genetic recombination in asexual species reduces genetic variety, making the populations less likely to adapt to environmental changes. There is some evidence that this is true, but it is a long-term disadvantage. However, natural selection cannot build a characteristic in order to prepare populations for future contingencies, and in the short term, asexual genotypes, because of their higher rate of increase, would be expected to replace sexual genotypes. [VI-21] Theoretical analyses have yielded several hypotheses of how sex can have a short-term advantage that prevents asexuals from taking over. In one hypothesis, environmental fluctuations continually favor new phenotypes for characteristics that are based on multiple genes, such as body size or disease resistance. Thus there is continual selection for new gene combinations, and therefore for genes that promote recombination, including genes for sexual reproduction. Another hypothesis holds that a parent will have more surviving offspring if they are genetically diverse, so that at least some of them have a chance of successfully competing for resources or resisting disease. Most of these and other hypotheses are rather new and have not yet been extensively tested, but there is evidence for some of them. For example, when grasses were grown in competition, the average growth of plants from sexually produced families exceeded the growth of plants from asexually (clonally) produced families, probably because various sexual genotypes used somewhat different nutrient resources in the soil. [REF Antonovics and Ellstrand] [VI-22] 11. Processes of coevolution of interacting species have been elucidated. Evolutionary ecologists, drawing not only on ecology but also genetics, phylogeny, and paleobiology, are developing and testing hypotheses about how species affect each others' evolution (coevolve) and how these processes affect the composition of ecological communities. For instance, the antagonism between prey and predators, and hosts and parasites (including microbial "microparasites" or pathogens), can lead to evolutionary "arms races", especially if each species interacts strongly with only a few species of antagonists. The adaptations that result can be intricate: plants, for example, have evolved diverse chemical defenses against herbivores, including compounds such as nicotine, caffeine, and salicylic acid (aspirin) that humans have used for diverse purposes. Each such defense, which is toxic or repellent to most herbivores, has been overcome by some insect species, which have evolved physiological mechanisms (most of which are poorly understood) to neutralize them. The vertebrate immune system is doubtless the most spectacularly complex defense ever evolved, but it is combated by parasites in many ways: trypanosome protozoans, such as the species that causes sleeping sickness, change their protein coat constantly, thus presenting the immune system with a moving target, and the HIV virus that causes AIDS undermines the immune system by attacking the T4 cells that are necessary for an immune response. [VI-23] An important outcome of studies of coevolution is that the process may or may not lead to stable coexistence. For instance, a parasite may evolve to be benign, or even beneficial to its host, if survival of the host enhances the parasite's own survival and reproduction. Many mutalistic interactions among species, in which each benefits from the association, have evolved from parasitic relationships. (For example, a group of small seed-eating wasps has given rise to those that pollinate fig trees. The specialized interaction between these pollinators and their host plants has given rise to several hundred species of figs, which are among the ecologically most important plants in tropical forests, where any mammals and birds depend on their fruit.) However, a parasite can remain virulent (harmful), or evolve to be more virulent, if this increases the number and of its offspring and/or their rate of transmission to other hosts. [MAY AND ANDERSON] The myxoma virus introduced into Australia to control rabbits evolved from a highly virulent to a moderately virulent state - but not to a benign state, even though benign virus genotypes are known to exist. Many instances are known in which parasites that have long been associated with their hosts are lethal. Depending on the biological details of the interaction, parasites may evolve to be benign, or to be so virulent that they extinguish the host population - and themselves. Evolution does not necessarily lead to stability, species survival, or harmony in nature. [VI-24] 12. Progress has been made in understanding how developmental processes evolve. A long-standing question is how complex anatomical characteristics, especially novel ones such as feathers in the first birds, evolve. An important part of the answer will come from understanding how the normal pathways of development of morphological features can change. This requires knowledge of the mechanisms of development, including mechanisms of gene action and of the cascade of developmental events (epigenesis) initiated by gene activity. The recent spectacular advances in developmental biology are paralleled by studies of evolutionary changes in developmental mechanisms. For example, we know that evolutionary changes in the timing of developmental events (heterochrony) can produce cascading, sometimes dramatic effects on morphology. In salamanders, evolutionary changes in genes that affect the production of hormones or the response of various tissues to these hormones influence the rate and timing of development, resulting in species that retain many larval characteristics throughout adult life. Such heterochronic changes, even if they affect only certain features, may have important, widespread effects; for instance, some salamanders that grow only to a miniature size fail to develop certain bones, and have skulls greatly altered to accommodate their relatively large eyes (Hanken et al). Molecular developmental studies in Drosophila have determined the identity and site of action of "master" switch genes, which regulate the action of genes, lower in the command hierarchy, that determine the identity and features of the segments of the insect's body. Comparative evolutionary studies show that homologues of these genes exist in other insects - and in mammals, echinoderms, and other animals It is suspected that in all these groups, these genes provide "positional information" that tells groups of cells where they are, and which lower-level genes to activate, but that the lower-level genes differ from one group of organisms to another, and so generate different characteristics. Remarkably, "master" genes that perform similar roles in the development of flowers and other organs of plants have some similarities in DNA sequence to the animals genes. [SIDEBAR? OR GOOD PHOTOS ON GENE EXPRESSION IN DROSOPHILA, LOCUST, MOUSE, ARABIDOPSIS; SEE S5 ABOVE] Most of the advances in evolutionary developmental biology are very recent: it is a field that is only beginning to flower. [VI-25] 13. Many aspects of human evolution have been elucidated. Major advances in the study of human evolution have issued from recent research, especially in paleoanthropology, phylogenetic systematics, and molecular population genetics. DNA sequences unequivocally show that our species is most closely related to the African apes, almost surely more closely to chimpanzees than to the gorilla. Indeed, we share more than 98% sequence similarity with these species. Moreover, the rate of sequence divergence among species has been calibrated by fossils of different primate lineages that have left living descendants [FIGURE OF HOW TO CALIBRATE?]. This calibration, applied to human/ape differences in DNA sequence, implies that the divergence of humans and chimpanzees from their common ancestor occurred about 6 to 8 million years ago. No fossils have yet been found of the common ancestor, but discoveries of early hominids (recognized by the anatomical signs of bipedal posture) with many ape-like features (such as a small brain, curved finger and toe bones, and dental features) are being made almost yearly in eastern Africa. The oldest confirmed hominid fossils so far discovered are about 4.4 My old, approaching the time of common ancestry suggested by DNA data. Several hominid species evolved and became extinct between then and now - the exact number is controversial - but collectively they show steady alteration toward the modern human condition in many features, such as improved capacity for bipedal locomotion, changes in the anatomy of hands and feet, and larger and larger brains [FIGURE - CRANIAL CAPACITY]. Some of the distinctions among the most recent named species - Homo habilis followed by Homo erectus followed by Homo sapiens - are arbitrary, for some fossil populations grade one into the other. [VI-26] By about one million years ago, Homo erectus had spread from Africa broadly across Eurasia. Brain size, as well as the sophistication of stone tools and other cultural artifacts, continued to increase. A major contemporary question is whether all these geographic populations left modern descendants, and were the progenitors of the geographic varieties of modern humans. The "multiregional" hypothesis holds that this is the case, and that genes for greater brain size and cognitive abilities spread among populations by gene flow. The "out of Africa" hypothesis, in contrast, maintains that Eurasian populations of Homo erectus and early Homo sapiens left few or no descendants: instead, all modern humans are descended from as few as 10,000 individuals in an African population that, in a second wave of colonization, spread into Eurasia (and thence to America and Australia) about 400,000 to 800,000 years ago, replacing the indigenous populations [DATES OK?] [VI-27] Although currently debated, DNA evidence tends to favor the "out of Africa" hypothesis [SEE SIDEBAR ]. The evidence is related to the idea of a "mitochondrial Eve" - the idea that all mitochondrial genes in today's human population are descended from those in a single woman less than a million years ago. (This doesn't mean that the human population consisted of only a single pair in the past; it means only that today's genes are descended from the genes of one member of an ancestral population, just as a single surname can predominate in an isolated town simply because most of the town's founders have left no great-great-grandchildren or great-great-great-great-grandchildren.) The evidence for this hypothesis comes from an intricate mathematical theory (coalescence theory) used to analyze the genealogy - the gene tree - of mitochondrial and other genes sampled from contemporary human populations. Greatly oversimplified, two considerations favor the "out of Africa" hypothesis. First, the basal branches of the gene tree appear to be represented by genes from African populations; genes from other populations are generally more similar in DNA sequence, and thus have probably diverged more recently from one another. This points to an African origin of the gene tree as a whole. Secondly, the time at which the branches in the gene tree developed, and the size of the population from which all the genes descended, can be estimated from the mathematical theory, given information on the rate of mutation (such information is indeed available). The long and the short of it is that if many ancient populations (more than a million years ago) had left living descendants, genes from Asia, Africa, and other regions would have accumulated far more mutational differences than they actually display. The observed high similarity of genes from all human populations, on the other hand, is exactly what we expect if they were descended from a single population, of rather small size, in the relatively recent past. ( REF Takahata) The mathematical analysis suggests an African population of about 10,000, about 0.4-0.8 million years ago, as the ancestor of today's human population. [VI-28] If, with further research, this hypothesis is indeed confirmed, it has the important implication that the genetic differences among modern human populations, including so-called "races", have had little time (on an evolutionary scale) in which to develop. Thus it is not surprising that although there are indeed some regional genetic differences in features such as skin color and the frequencies of blood groups, all human populations are, overall, genetically very similar. Most human genetic variation is within, rather than, among populations. Thus, if all humans were to become extinct except for a single tribe somewhere on earth, at least 85% of the genetic variation that exists today would still be present in the future population that grew from the survivors. (REF Lewontin; Nei and Roychoudhury) [VII] CONTRIBUTIONS OF EVOLUTIONARY BIOLOGY TO THE BIOLOGICAL SCIENCES [VII-1] Earlier in this century, most biologists were broadly trained, so that many brought both a mechanistic perspective and an evolutionary perspective to their research. Many geneticists, for example, were motivated by evolutionary questions, and contributed to both evolutionary theory and to our understanding of genetic mechanisms. Herman Muller, for instance, made many important contributions to evolutionary genetics, and also won a Nobel Prize for discovering that radiation causes mutations. With the growth in science and the explosive growth in information, biology became increasingly fragmented into specialized subdisciplines, and biologists became increasingly narrowly trained. Hence many biologists who work in areas such as molecular biology and neurobiology have little background in evolutionary biology, and are unaware of its potential contributions to their disciplines. Likewise, many evolutionary biologists lack sufficient training in some of the mechanistic biological disciplines. Nevertheless, mutual influences between evolutionary biology and the other biological disciplines have continued, and in some areas have recently become more pronounced. We can sketch only a few of the ways in which evolutionary data and approaches have made recent contributions to other biological sciences. [VII-2] Molecular biology. [VII-2A] Ribosomal RNA has a secondary structure, composed of loops of unpaired sequence and stems of Watson-Crick pairs of bases. Chemical and biophysical methods, such as X-ray crystallography, provided some information on the structure of small RNAs, but was ineffective in resolving the structure of large RNAs. However, phylogenetic analysis of sequences from diverse species identified the evolutionarily conserved regions, providing the basis for specifying those portions of the molecule that maintain secondary structure by Watson-Crick pairing. Thus inference from evolutionary analysis provided the fundamental data on the structure of these ubiquitous, critical components of the protein-synthesizing machinery. In reviewing the structure and function of the ribosome in the Annual Review of Biochemistry, H. F. Nollar wrote, "Supporting all of this are the broad underpinnings of phylogenetic comparison, bringing the evolutionary perspective to bear not only on questions of evolution per se, but on the actual details of the structure and mechanism of this ancient machine." [NOLLAR 1984, ANNU. REV. BIOCHEM. 53:119-62] [VII-2B] The genome of eukaryotic organisms, including mammals, varies greatly in DNA content, due to variation in the often huge numbers of repeated sequences. These, moreover , vary greatly in sequence and organization. For many years, there was confusion and controversy among molecular biologists about the function of these components of the genome. In April 1980, papers by Doolittle and Sapienza and by Orgel and Crick independently announced the "selfish gene hypothesis" as "the best way to make sense of the puzzles and paradoxes ... [which are] ... so odd that only a somewhat unconventional idea is likely to explain them" (Orgela and Crick, p. 607). The selfish gene hypothesis is, simply, that the repeated DNA serves no function for the organism, but is propagated because any DNA sequence that can successfully replicate and be transmitted to subsequent generations has a selective advantage, by the very definition of natural selection, over sequences that are less capable of doing so. As Orgel and Crick acknowledged, this idea had been sketched four years earlier by the evolutionary biologist Richard Dawkins in his book The Selfish Gene. The wise acceptance of this evolutionary theory has reshaped much of the mechanistic research on these sequences. [VII-2C] The genetic code is redundant. Many of the amino acids that compose proteins are encoded by several nucleotide triplets (codons) that differ in the third position. The several synonymous codons might be expected to be equally frequent in the DNA, but very often one is far more frequent than the others, a pattern called "codon bias." Molecular evolutionary biologists have reasoned that natural selection may be responsible for such patterns. Such selection must be weak, since synonymous codons do not differ in the protein products that carry out the biochemical functions on which the survival of the organism depends. Population genetic theory predicts that weak selection will be more effective in large than small populations. As this theory predicts, codon bias is more pronounced in organisms such as bacteria and yeast, which have huge populations, than in mammals, which have much smaller populations. Thus it is indeed likely that natural selection chooses among synonymous DNA sequences, and the question now is what the mechanistic differences are among synonymous sequences that might affect survival or reproduction. A leading hypothesis is that translation of messenger RNA into protein may be more efficient if a common codon, rather than a variety of different codons, interacts with the transfer RNAs involved in protein synthesis. [BULMER IN OXFORD SURV. EVOL. BIOL.] Evolutionary research thus points the way to research on fundamental molecular mechanisms. [VII-3] Developmental biology [VII-3A] The relationship between the study of evolution and the study of how individual organisms develop has been long and turbulent. Similarities among the embryos of species that differ radically as adults were among Darwin's chief sources of evidence for evolution. Much of embryology in the decades after Darwin focused on relationships between phylogeny and development, as in Ernst Haeckel's famous, and erroneous, "law" that the ontogeny of an organism replays the history of adult characteristics of its ancestors. Thus, embryology was concerned with differences in development among organisms, and on development as a source of evidence for phylogenetic relationships. Early in the twentieth century, attention shifted to the mechanisms of development, and embryology became an experimental science, largely divorced from evolutionary studies. Nevertheless, some few individuals, such as Julian Huxley, Gavin deBeer, Richard Goldschmidt, and Conrad Waddington, maintained a bridge between the fields, both contributing to fundamental developmental biology and emphasizing to their evolutionary colleagues that a full understanding of evolution requires an understanding of developmental phenomena. They emphasized, for example, that genes govern the rates of developmental events, such as the elongation of digits, and that changes in these genes would cause differences in shape among species. Developmental biologists, likewise, acknowledged that some embryological phenomena could be understood only by evolutionary history. The notochord, for example, makes only a brief appearance in the development of most vertebrates, only to disappear. It plays an essential role, for it induces the development of the nervous system; but that the notochord should exist at all is explicable only by the fact that it is a functionally important structural feature throughout life in primitive vertebrates. The developmental role of inducing the nervous system evolved early in vertebrate history, and the notochord has been retained in the embryos of advanced vertebrates because of this developmental role, long after its structural function was replaced by the evolution of the bony spinal column. [VII-3B] Despite such instances of union, however, developmental biology and evolutionary biology have been largely divorced for several decades. During this time, evolutionary biology has contributed to studies of developmental mechanisms chiefly by describing the diversity and phylogenetic relationships among organisms used for experimental studies. Many developmental phenomena have been elucidated, for example, by cross-species transplants. For instance, when epidermis of lizard embryos is grafted onto the dermis of mouse embryos, it is induced to develop scales in the spatial pattern typical of mouse hairs, illustrating that a common mechanism of induction of one tissue by another has been retained for many millions of years, but that the response of the induced tissue is determined by a species' genetic makeup. [DHOUAILLY CITED IN FUTUYMA 1986] [VII-3C] A resurgence in interaction between developmental and evolutionary biology is now under way, in part because of renewed focus on development by evolutionary biologists, and in part because of comparisons among species of the genes that have been identified as playing critical roles in development. For example, both developmental and evolutionary biologists are gaining insights from comparisons of the homeotic genes that are found in animals as distant as insects and mammals, and which play similar roles in determining the development of the basic body plan in both. As another example, the comparative approach has provided critical insights into the function of major genes involved in eye development and into the mechanisms of eye morphogenesis. Walter Gehring and his research group at the University of Basel, Switzerland, have recently discovered that a similar system of genetic control of eye development prevails in insects and mammals, and may apply to all animals. The key feature of this genetic system is a single "master control" gene that initiates eye formation and appears to regulate the activity of the many other genes that contribute to eye development. [HALDER,G., P. CALLAERTS AND W.J. GEHRING. 1995. SCIENCE 267:1788-1792] [VII-3D] The eyeless (ey) mutation, which causes partial or total loss of the compound eyes in Drosophila, was first described in 1915. A fly with extra copies of the normal allele of this gene develops extra eyes. The small eye mutation, which causes partial or total eye loss in mice and rats, was discovered in 1967, and is now known to be one of a group of genes that produce transcription factors which regulate the activity of other genes. By DNA sequencing, Gehring and associates discovered that eyeless, small eye, and a human mutation with similar effects, called aniridia, are the same gene. They postulated that this gene may function as the master gene for eye development in all three species, despite the radically different anatomy of insect and vertebrate eyes. In a stunning experiment, they inserted the mouse gene into the Drosophila genome, and obtained flies with extra eyes, the same result as when flies carry extra copies of their own gene! If, as these authors believe, the presence of the same master gene for eye development in animals as distantly related as insects and vertebrates means that the gene was associated with eye development, or at least with light reception, in their common ancestor (more than 550 million years ago), then it is likely that eye development in other animals is regulated in the same way. This prediction has been borne out by preliminary studies, which have identified the presence of this gene in flatworms and ribbon worms, two of the most primitive groups of animals with eyes. [VII-3E] Discovery of a common genetic basis for the control of eye development has enhanced our understanding of, and appreciation for, the operation and lability of developmental mechanisms, while at the same time posing new questions about those mechanisms. For example, the anatomy of the eye in insects and vertebrates is so different that the image-focusing ability of the eye has surely evolved independently in the two groups. This means that the developmental-genetic control of eye development is probably distinct from the determination of the particular array and configuration of the structures formed. This information helps to pinpoint the most promising ways in which to study eye morphogenesis. Commonality in important features of eye development also has a practical benefit. Insects and other animal species that are easier and less costly to study than humans can be used as models for improving our understanding of the developmental and genetic bases of human congenital and hereditary malformations, such as aniridia, as well as their diagnosis and possible treatment, with the confidence that knowledge derived from such species can be applied meaningfully to humans. [VII-4] Physiology [VII-4A] Evolutionary biology has long influenced the study of physiology in animals and plants, and can make many other contributions that are only now being developed. Some of these contributions can affect human physiology, including related areas such as sports medicine and clinical psychology. The logical perspectives, methods, and comparative data of evolutionary biology can advance our understanding of basic physiological mechanisms and their applications to areas such as medicine, agriculture, and veterinary science. Evolutionary physiology includes comparisons of physiological features among species, phylogenetic analysis of the evolution of physiological characters, and population genetic approaches to physiology. [GARLAND AND CARTER 1994] [VII-4B] Comparative physiology, or physiological ecology, is the study of physiological functions in species that occupy environments that differ in temperature or other variables. For much of its history, this subject has taken the principle of adaptation as a guide to analyzing function, and has studied the ways in which species are physiologically adapted to their environments. The result has been discovery of many fascinating mechanisms that deepen our understanding of physiology and biochemistry. For instance, proteins have been characterized that prevent the formation of ice crystals in the cells of Antarctic fishes that live in waters near the freezing point, and studies of diving mammals such as seals have provided insight into how these animals can function without breathing for long periods at high pressure -- data that bear on the physiology of human divers. More recently, evolutionary physiologists have recognized that, contrary to the guiding paradigm in previous studies, species are not necessarily perfectly adapted to their environments. For instance, the hypothesis of optimal adaptation suggests that each anatomical feature involved in a complex physiological function should be matched to the other parts so that no one part limits function. The diameter of the trachea should deliver neither more nor less air to the lungs than the lungs can use, for example. A more sophisticated evolutionary approach, however, recognizes that we need not expect such a perfect match, and indeed the matches, when tested, have proved to be imperfect. [VII-4C] The comparative approach to physiology, undertaken by evolutionary biologists interested in mechanisms of adaptation, may have implications for human health. For example, studies of lizards indicated that high body temperature, accomplished by basking under heat lamps, had beneficial effects on recovery from experimentally induced infections. This suggests a new perspective on fever in humans, raising the hypothesis -- yet to be tested -- that mild fevers might be advantageous and should not be controlled by drugs. [NESSE AND WILLIAMS 1994] Another example bears on the regulation of blood pH during open-heart surgery. [WHITE 1989] Usually, such surgery is facilitated by cooling the body and thus slowing the heart rate. Cooling the body raises blood pH, and clinicians have seen this as a "problem", to be solved by adjusting the pH to the level found at the body's normal temperature (37oC). However, comparative physiologists have pointed out that blood pH normally rises with body temperature in ectothermic animals such as reptiles, with no adverse effects. This recognition has led to changes in the way surgical hypothermia is managed. [VII-4D] The theory and methods of evolutionary genetics contribute both to understanding the basis of variation in physiological functions within species and to describing physiological mechanisms. These methods, for example, have been widely used to describe the extent to which physiological differences among individual organisms are due to genetic differences versus individual adjustments (acclimation) to temperature or other variables. An important method is artificial selection on physiological characteristics. Such human-induced evolutionary changes in experimental populations of various species have shown that genes influence individual variation in characteristics such as alcohol tolerance, temperature tolerance, and learning ability. In populations that have been altered by artificial selection, a search for characteristics that have undergone a correlated change can then reveal candidates for physiological mechanisms. For instance, changes in ion channels have been correlated with changes in alcohol toxicity in selected populations [OF WHAT? CHECK DETAILS IN HARRIS AND ALLAN 1989, FASEB JOURNAL 3:1689-95] Likewise, traits that may affect senescence are being sought in experimental populations of Drosophila and the nematode Caenorhabditis elegans in which delayed maturity has been achieved by artificial selection. [ROSE 1991, JOHNSON 1990] Investigators are mapping the genes that affect open-field behavior (an index of anxiety in novel situations) in selected lines of mice; once candidate genes have been identified, they can be cloned and sequenced, leading to an understanding of their specific physiological function e.g., the protein they produce). [FLINT ET AL 1995, SCIENCE 269:1432-35] In other studies, mouse populations are being selected for differences in activity levels, with the aim of determining whether or not such differences affect health or lifespan, or perhaps female reproduction (as occurs in humans). Because the data on humans are non-experimental and difficult to interpret, such studies of animal models are important. [VII-5] Neurobiology and behavior [VII-5A] From its inception, the field of animal behavior has had a strong evolutionary base, for its goals have included understanding the evolutionary origin of behavioral traits and their adaptiveness. Behavioral traits evolve, just as do morphological characteristics, and like morphology, they are often more similar among closely related than distantly related species. Phylogenetic studies of behavior have provided examples of how complex behaviors, such as the courtship displays of some birds, have evolved from simpler ancestral behaviors. [VII-5B] Evolutionary biologists have worked extensively on the relative contributions of genes and experience (learning, in the broad sense) to variation in behavior, and have shown that these differ, depending on the trait and on the species. In an effort to understand how natural selection has acted on the genetic component of variation and shaped adaptively important behaviors, evolutionary biologists have developed a wide range of mathematical models that predict the behaviors that may evolve, depending on a species' ecological and social environment. Some of these are related to economic models. For instance, models of foraging behavior have successfully predicted the foraging "decisions" made by birds and other species in the face of variation in the quality and spatial distribution of food. Other models are drawn from game theory, such as the theory of "evolutionarily stable strategies" (ESS) that, among other things, predicts when animals fighting over food or mates will withdraw versus escalate the conflict. ESS models have wide application; for instance, they can explain why in some species, only one parent cares for the offspring, whereas both parents do so in other species. This theory relies on the insight that the interests of the two parents may conflict: one parent may gain fitness from the other's helping to rear offspring, whereas the other may gain fitness by defecting, and searching for additional mates. [VII-5C] The evolutionary study of animal behavior has joined with comparative psychology in several research areas, such as the study of learning. It is now clear that natural selection has fostered the ability to learn different tasks in different species, and that adaptations for learning such tasks can be studied in much the same way as morphological adaptations. For instance, closely related species of gulls differ in their ability to distinguish their own offspring from others', depending on whether or not the nests of the species are typically arranged so that offspring are likely to mingle. Species of birds differ markedly in their ability to remember sites in which food has been stored, this ability being extremely high in those species that typically cache seeds or other food. [VII-5D] Although neurobiologists recognize that the mechanisms they study are adaptations, they generally do not study behavioral mechanisms in expressly evolutionary terms. So far, evolutionary biology has not contributed to understanding molecular processes in neurobiology, and the points of contact between neurobiology and evolutionary biology have been rather few. There are some notable exceptions, however. The adaptive perspective of comparative evolutionary biology had led to the discovery of interesting sensory and behavioral mechanisms. For instance, the sonar systems of bats, both the production and reception of sound, differ according to the species' environment and typical prey. Species that glean insects from leaf surfaces have an entirely different sonar system from species that catch aerial insects. The study of neuroanatomy has been revolutionized by comparative and evolutionary perspectives: differences among species provide insights into the function of brain regions. Students of bird song first found that the size of different portions of the brain change with the seasons as the use of these regions wax and wane. Likewise, the size of the song-controlling region of the brain differs among populations and species of birds that differ in the number of different songs they sing. More recently, comparative studies have shown that species that depend on certain mental capacities have greatly enhanced brains in the relevant regions, such as those that control memory of locations in species of jays and mice that store seeds in hundreds of sites. In some species of owls that can accurately locate prey in total darkness, clusters of brain cells that process information on sound are so spatially organized that they form a literal map of the three-dimensional environment from which sounds are received. Comparative studies of this kind, based on understanding the adaptive requirements of different species, thus lead to new investigations of behavioral mechanisms. **** ADD SOMETHING ON HORMONAL CONTROLS -- LES REAL?? *** [VIII] EVOLUTIONARY BIOLOGY: MEETING SOCIAL NEEDS [VIII-1] Directly and indirectly, the many subdisciplines of evolutionary biology have made innumerable contributions to meeting social needs. Space limits us to mention here only a few examples from some of the many areas of application. We focus especially on contributions to human health, agriculture and renewable resources, natural products, environmental management and conservation, analysis of human diversity, and extensions of evolutionary biology beyond the realm of the biological sciences. [VIII-A] Human Health and Medicine [VIII-A1] Two major areas in which evolutionary principles and methods are critically important are genetic disease and infectious disease. Genetic diseases are carried in part by variant genes or chromosomes, although expression of the condition often is influenced by environmental (including social and cultural) factors and by an individuals' genetic constitution at other loci. To diseases caused by genetic variants, we might add common or virtually universal conditions, such as senescence, that require medical attention and research. Infectious diseases are caused by parasitic organisms such as viruses, bacteria, fungi, and helminths (worms). Their effect on health may vary, depending on a person's genetic constitution and nutrition and other environmental factors, as well as on the genotype of the infecting organism. Control and treatment of infectious disease requires not only medical but ecological research and actions. [VIII-A2] Genetic disease. Each of the vast number of genetic diseases is caused by alleles at one or more genetic loci, that range in frequency from very rare to moderately common (as in sickle-cell disease and Tay-Sachs disease, which are rather frequent in some populations). Allele frequencies are the subject of evolutionary (population) genetics, which is readily applied to two tasks: determining the reasons for the frequency of a deleterious allele and estimating the likelihood that a person will inherit the allele and/or develop the trait. Thus, for example, the high frequency of sickle-cell and several other defective hemoglobins signaled to population geneticists that some agent of natural selection probably maintained these genes in populations. Their geographic distribution suggested an association with malaria, and subsequent research confirmed that the genes are prevalent because heterozygous carriers have greater resistance to malaria. This is a clear instance of the theory, developed by evolutionary biologists decades before the sickle-cell pattern was described, that a heterozygous fitness advantage maintains genetic polymorphism. (Allison). [IS THIS A CORRECT HISTORY?] [OTHER EXAMPLES? CAN WE SAY WHY KNOWLEDGE OF THIS MATTERS?] [VIII-A3] It is important for couples to know the likelihood that their children will inherit genetic diseases, especially if these have occurred in the family history. Genetic counseling has provided such advice for many decades. Genetic counseling is applied population genetics, for it relies on both pedigree analysis (standard genetics) and knowledge of the frequency of a gene in the population at large to calculate the likelihood of inheriting a genetic defect. Likewise, evaluating the health consequences of increased marriage among related individuals or of increased exposure to ionizing radiation and other environmental mutagens depends critically on theories and methods developed by population geneticists. [VIII-A4] Molecular biology is revolutionizing medical genetics, since the technology now exists to locate genes, determine their sequence in the hope of determining the causative difference between deleterious and normal alleles, identify carriers of defective alleles from small samples of DNA (including those obtained by amniocentesis), and potentially to employ genetic therapy whereby normal alleles can be substituted for defective ones. Methods and principles developed by evolutionary biologists have contributed to these advances, and are likely to make other contributions in the future. For instance, locating a gene for a particular trait is no easy task. It relies on associations between the gene sought and linked genetic markers. The consistency of association with such markers - whether or not a marker on any one person's chromosome will signal the presence of a deleterious allele in its vicinity - is the degree of "linkage disequilibrium". Linkage disequilibrium is a major topic in population genetics, for it plays an important role in many evolutionary processes. Thus theory has been developed to predict the degree of linkage disequilibrium as a function of such factors as allele frequencies, recombination between genes, and population size. Applying this theory was instrumental in one of the first cases in which a deleterious gene - the one causing cystic fibrosis - was located and subsequently sequenced. The same theory also tells us why linkage disequilibrium will not work in mapping every disease gene. As the effort to real the promised rewards of the Human Genome Project moves toward understanding complex genetic diseases, the role of theories from evolutionary genetics will grow. [VIII-A5] Determining which of the many nucleotide differences between a deleterious allele and a normal allele causes a disease is important for understanding how its effects may be remedied. Molecular evolutionary studies have given rise to several methods that can help to distinguish variation in a gene sequence that strongly affect fitness (by affecting function) from those that are relatively neutral. These methods employ analysis of sequence variation both within species and among closely related species. We predict that these methods, including comparisons among human genes and their homologues in other primates, will contribute to identifying the lesions that cause genetic diseases. In this context, data banks of gene sequences from many species, as well as the Human Genome Project that will ultimately sequence the entire human genome, will provide (as it already does, with more limited data) abundant opportunities for comparing gene sequences among species. For instance, a genetic defect causing a neurological disorder in humans is associated with a genetic sequence that most closely matches the "mariner" transposable element of lacewing flies. This element, first described in Drosophila, is now known to occur in mosquitoes and many other insects, and might have been transferred to humans from an insect carrier. Comparisons among sequences from different species also holds promise for identifying the normal function of defective genes. [VIII-A6] Infectious disease. In the analysis and control of infectious diseases, the critical questions include: What is the disease-carrying organism? Where did it come from? Do other host species act as reservoirs? How is it spread? If spread by a vector such as an insect, how far does the vector typically disperse, and what other ecological properties of the vector might be exploited to control the spread? How does the organism cause disease, and how might it be treated by drugs or other therapies? How does it reproduce, sexually or asexually or both? Is it likely to evolve resistance to drugs or the body's natural defenses? Is it likely to evolve greater or lesser virulence in the future, and under what conditions will it do so? To each of these questions, evolutionary biology can and does contribute. [VII-A7] Identifying the organism, and its vector if there is one, is a matter of systematics, an evolutionary study area. If, like HIV, it is a previously unknown organism, phylogenetic systematics is absolutely essential to tell us what its closest relatives are, which immediately provides clues to its area of origin, other possible host species, and many of its likely biological characteristics, such as its mode of transmission. If a new species of malaria-causing protozoan (Plasmodium) should be found, for example, we can confidently predict that it is vectored by Anopheles mosquitoes, like other Plasmodium species. Similarly, identifying disease vectors, using the methods of systematics, is essential. Progress in controlling malaria in the Mediterranean region was slow until it was discovered that there are six almost identical species of Anopheles mosquitoes, differing in habitat and life history, only two of which ordinarily transmit the malarial organism. Using techniques of phylogeny and population genetics, the geographic region of origin of a new disease may be identified, as well as other species from which the organism may have spread to humans. The Human Immunodeficiency Viruses (HIV), for example, appear to have spread into the human population from two distinct monkey-borne viruses, probably long before they were detected. [ SIDEBAR #7 ON ORIGINS AND GENETIC DYNAMICS OF HIV: CONTRIBUTION FROM HOLMES, PERHAPS WITH MORE DETAIL] [VIII-A8] The methods of population genetics, applied to DNA sequences and other variable genetic markers, are indispensable for discovering the mode of reproduction of pathogens and their animal vectors, as well as their population structure -that is, the sizes and rates of exchange between local populations. For example, by using multiple genetic markers to study Salmonella and Neisseria meningitidis, the cause of meningococcal disease, population geneticists have found that both of these pathogenic bacteria reproduce mostly asexually, but occasionally transfer genes by recombination, even among distantly related strains. The immunological variations in cell-surface proteins and lipids that bacteriologists have traditionally used to classify strains of these bacteria are not well correlated with the genetic lineages revealed by multiple genetic markers, nor with variation in pathogenicity or host specificity. Thus, predicting these traits in public health studies will require using multiple genetic markers. [CAUGANT ET AL 1987, J. BACTERIOL. 169:2781-92; BELTRAN ET AL. 1988, PNAS 85:7753-57] Similarly, population genetic methods can estimate rates and distances of movement of disease vectors, which affect both disease transmission and potential for control. Identical molecular features of an allele for insecticide resistance in a species of mosquito showed that the allele had recently spread among three continents, evidence of this insect's enormous dispersal capability. [REF] [VIII-A9] The potential rapidity of evolution in natural populations, especially in microorganisms with short generations and huge populations, has exceedingly important implications. One, an evolutionary lesson that should have been heeded long before it was, is that pathogens may be expected to adapt to consistent, strong selection, such as that created by widespread, intense use of therapeutic drugs. Antibiotic resistance has evolved in HIV, the tuberculosis bacterium, the gonorrhea bacterium, the malarial protozoan, and many other disease-carrying organisms, rendering many traditional antibiotics useless. Many of these organisms, indeed, are resistant to multiple drugs. (Solely in economic terms, the cost of failed therapy and development of new therapies, required by microbial evolution, is about $[???] per year.) [CHECK NEU 1992, SCIENCE 257:1064-73 FOR POSSIBLE DATA] Molecular comparisons of resistance genes, often carried by extrachromosomal pieces of DNA (plasmids), have shown that they are commonly transferred from one species of bacterium to another, even among distantly related species. Natural populations of bacteria carry genes that readily confer resistance to certain antibiotics, namely those that are chemically similar to antibiotics naturally produced by some species of fungi. (Penicillin was isolated from one such fungus.) [POSSIBLE FIGURE FROM DAVIES 1994, SCIENCE 164: 375-381 ON RESISTANCE GENES] Studies of the evolution and mechanisms of antibiotic resistance suggest that this evolutionary process can be retarded by more judicious, sparing use of any single antibiotic, and potentially provide insights into how the resistance mechanisms might be countered. [EXPAND?] [VIII-A10] Not only antibiotic resistance, but also the virulence of pathogens can evolve rapidly. The theory of parasite/host coevolution predicts that greater virulence may evolve when opportunities for transmission among hosts increase. Some authors have postulated that major outbreaks of influenza and other pandemics have been caused by such evolutionary changes that transpired in crowded cities and among mass movements of refugees. Likewise, there is suggestive evidence that higher virulence of HIV has evolved, due to high rates of transmission by sexual contact and sharing of needles by intravenous drug users.[EWALD; CHECK ALSO REFS IN MASSAD 1996, EVOLUTION 50:916] It is well established that the population of HIV viruses in an infected person evolves during the course of the infection, and some authors attribute the onset of AIDS - the disease itself - to this genetic change. [NOWAK ET AL 1990, AIDS 4:1095] [VII-A11] Normal physiological functions. Understanding the human body's natural defense systems against infectious disease is as important as understanding the diseases themselves, and here too evolutionary biology can work hand in hand with medical science. For example, genes in the major histocompatibility complex (MHC) can play a critical role in cellular immune responses; their products carry foreign proteins to the cell surface and present them to the immune system. The MHC thus is important in the body's ability to distinguish "self" from "nonself," and contributes to rejection of tissue transplants. Moreover, some MHC alleles are associative with autoimmune diseases such as juvenile diabetes and ankylosing spondylitis. Genetic variation in the MHC is exceedingly great. As with other polymorphisms, this has led population geneticists to seek reasons for the variation. Molecular analyses have revealed that the genes must be under some kind of balancing selection that maintains variation. In fact, some human genes are genealogically closer to some chimpanzee genes than to other human genes, which provides clear evidence that balancing selection has maintained variation for at least five million years. The variation is almost certainly maintained by the role different genes play in combating different species and genotypes of pathogens, but the exact role requires further study. (?Takahata et al, Genetics 130:925-38) [VIII-B] AGRICULTURE AND NATURAL RESOURCES [VIII-B1] Plant and animal breeding. The relationships among geneticists, agricultural scientists, and evolutionary biologists have such a long and intimate history that these fields are sometimes hard to distinguish, especially in the area of artificial selection, i.e. breeding improved varieties of crops and domestic animals. Darwin opened The Origin of Species with a chapter on domesticated organisms and wrote a two-volume book on Variation in Plants and Animals Under Domestication. One of the founders of population genetics, Sewall Wright, worked for a while in cattle breeding, and another, R.A. Fisher, contributed importantly to the design and analysis of crop trials. Since then, the careers of many geneticists have consisted of equal contributions to evolutionary genetics and to the basic genetics and theory required for effective selective breeding. Concepts such as heritability, components of genetic variance, and genetic correlations, as well as experimental elucidation of phenomena such as hybrid vigor, inbreeding depression, and the basics of polygenic (quantitative) variation play equally central roles in agricultural genetics and evolutionary theory. The most recent example of this mutualistic interaction between fields is in the development and application of molecular markers to locate the several or many genes ("quantitative trait loci") responsible for continuously varying traits, such as fruit size and sugar content, and then to identify the metabolic function of these genes. In the past, only a few model organisms, such as Drosophila, were genetically well known enough to provide and such information, Now, due to research by crop geneticists, population geneticists, and the Human Genome Project, it is possible to map the genes of interest in virtually any organism, whether it be a domesticated species or a wild species used for evolutionary studies. [VIII-B2] Genetic variation, the stock in trade of evolutionary biologists, is the sine qua non of successful agriculture. Any evolutionary biologist would predict that a widely planted genetically uniform crop will be a sitting duck for plant pathogens or other pests, which will adapt and spread rapidly. The potato blight that caused widespread famine in Ireland in the 1840's is one of many examples in which a plant pathogen has adapted to a widely planted, genetically uniform crop. [ADAMS ET AL. 1971, BIOSCIENCE 21:1067-70] Another spectacular example is the epidemic of southern corn leaf blight in the United States in 1970, which caused an estimated economic loss of $1 billion. More than 85% of the acreage of seed corn had been planted with strains carrying a cytoplasmic genetic factor (Tcms) for male sterility. (This genetic factor, preventing development of male flowers, was useful for producing uniform, desirable, hybrid varieties.) The Tcms factor made corn hypersusceptible to a mutant race of the fungus Phytopthora infestans, which rapidly spread through the Corn Belt and beyond. Only a combination of weather and widespread planting of corn with normal cytoplasm prevented an even more devastating blight in 1971. [ULLSTRUP 1972, ANNU. REV. PHYTOPATHOL. 10:37-50] Despite such lessons, genetically uniform crops are still widely used, for reasons of economic efficiency, but it is widely recognized that it is essential to maintain genetic diversity. [NAS, NRC 1972, GENETIC VULNERABILITY OF MAJOR CROPS, WASHINGTON, D.C.] Thus it is essential to build up "germ plasm" banks of different strains, especially with an eye to strains that differ in characteristics such as drought tolerance and pest resistance. An important source of potentially useful genes is wild species related to the crop -- which of course can be recognized only on the basis of good systematics and phylogeny. For example, the cultivated tomato, like most crop species, is a self-fertilizing (and therefore genetically homozygous) species that harbors little genetic variation even among all the available varieties. It originated in Andean South America, and made its way to North America via domestication in Europe. Studies of the genetics and evolution of the tomato led to the realization that many related species are native to Chile and Peru, and that these carry a wealth of genetic variation. More than 40 instances of resistance to major diseases have been found among these species, and 20 of them have been transferred into commercial tomato stock, by hybridization. Fruit quality traits have also been improved in this way, and drought-, salinity-, and insect pest-resistance are expected to be introduced in the next few years, for an estimated 4- to 5-fold increase in agricultural yield. [NEED REFERENCE: CHUCK] [VIII-B3] Using biodiversity. Knowledge of the systematics of tomatoes, together with ecological genetics and an understanding of the plant's breeding system, formed a foundation for a successful application that could be repeated for many other crops (and has been, in several other cases). New genetic technology, namely genetic engineering that makes it possible to transfer genes from virtually any species into any other, is rapidly developing. This makes available, for agricultural and other purposes, the vast "genetic library" of the world's organisms, which among them carry a tremendous variety of genes for heat tolerance and other physiological traits, disease and insect resistance, chemicals that impart flavors and odors, and many other potentially useful features. To use this library in the future, it is necessary both that the library be preserved - i.e. that biodiversity not be lost - and that there be librarians: scientists who can provide some guidance toward useful volumes. The librarians are evolutionary biologists: those who study systematics and phylogeny, and so know what the species are and which are likely to share similar genes and characteristics, and those who study evolutionary genetics and adaptation, and are best able to point the way toward organisms with desirable traits. For example, the Indian neem tree, obscure until recently, contains one of the most potent insecticides known (azidirachtin), and evolutionary ecologists who study insect/plant and fungus/plant interactions can point toward many other promising candidates. [BERENBAUM: HELP WITH DETAILS] [VIII-B4] Pest management. Plant pests, chiefly insects and fungi, take an enormous economic toll in losses and control measures annually. Evolutionary biology bears on this issue in many ways. Quite aside from the dangers to public health and the environment of excessive use of chemical pesticides, more than 400 species of insects (crop pests, pests of stored grains, disease vectors) have evolved resistance to one or more insecticides in the last 40 years, and some are resistant to all known insecticides. The evolution of pesticide resistance has added $1.4 billion to the annual cost of crop and forest product protection in the United States. [PIMENTEL ET AL 1992, BIOSCIENCE 42:750-760] Agricultural entomologists trained in evolutionary genetics are developing methods to delay or prevent the evolution of resistance, such as rotational use of different control measures and judicious combination of chemical with nonchemical control (integrated pest management, IPM). Two nonchemical methods have profited greatly from evolutionary knowledge and theory: use of natural enemies and resistance breeding. [VIII-B5] Natural enemies, such as insects that are specialized predators or parasites of the pest species, are an important method of control. Very often these are sought in the pest's region of origin. (The majority of pest insects have been accidentally introduced into the regions where, because their natural enemies are absent, they are most damaging.) The first question is where the pests come from. This requires entomologists trained in evolutionary systematics, who may be able to identify the insect - using a taxonomy based on evolutionary principles. If the insect is an unknown species, the best clue to its region of origin is the distribution of related species - i.e. using evolutionary taxonomy. The search for natural enemies uses the same principle. Once potential enemies, such as parasites, have been found, it is critical to distinguish closely related, very similar species, for some may attack the pest and others may attack only its relatives. It is then necessary to determine many of the life-history and other features of the parasite, to be sure it will not itself cause damage (e.g., by attacking either, useful species) and to determine if it is likely to prosper in its new home. If it is approved for introduction, large numbers must be bred for release. At this stage, evolutionary genetics is crucial, to prevent the parasite stock from becoming inbred or unconsciously selected for characteristics, such as sluggishness, that could impair its effectiveness. [VIII-B6] Another major pest management strategy is to select for resistance in the crop, by screening for genes that provide resistance in the laboratory or field plots, and then crossing the genes into cultivars with other desirable characteristics. The genetic basis of resistance is important, for some kinds of resistance are short-lived. The pest may adapt to a resistant strain as readily as it adapts to chemical insecticides. For example, at least 6 major genes for resistance to Hessian fly have been successively bred into wheat. In each case, within a few years of widespread planting of the new strain, the fly has overcome the resistance: for every resistance mutation in the plant, a corresponding mutation in the fly nullifies the effect. A major current thrust is to engineer resistance by transferring to the plant genome resistance genes from other species; for example, an insecticidal toxin from a bacterium (Bacillus thuringiensis, or BT) has been incorporated into tobacco. However, it has already been shown that the tobacco budworm can rapidly adopt to BT-engineered plants. [GOULD REF] Entomologists and plant breeders trained in evolutionary biology are working on methods of multiple resistance to lengthen the effective life of new resistant cultivars. Others are working on ways to turn the pest's biology against itself, such as using plant compounds that mimic insect hormones. [VIII-B7] Genetic Engineering. Proposals abound for introducing various traits into crop plants and for broadcasting engineered bacteria that can improve soil fertility or impart frost resistance to certain crops. Questions about potential risks arise when such deliberate introductions are proposed. Evolutionary biologists who study gene interactions have noted the need for tests to be sure that a foreign gene does not unpredictably interact with a crop plant's loci to generate harmful effects. A perhaps more likely risk is that genes could spread by cross-pollination into wild plants related to the crops (e.g. wild mustards related to rape seed and cabbage) and cause them to become more vigorous weeds. Likewise, because genes are often transferred between species of bacteria, there has been concern that natural bacterial populations could acquire features that render them more vigorous and potentially harmful.. Thus methods developed by evolutionary biologists in their basic scientific work acquire valuable applications: assessing the fitness effects of genes, and measuring the rate of gene exchange among populations and species. [SPECIFIC EXAMPLE FROM PAST STUDIES?] [VIII-B8] Forestry and Fisheries. The genetic structure of populations and species, a major area of evolutionary biology, is revealed by statistical analysis of genetic markers. These methods, widely used in evolutionary studies, have many applications. They enable one, for instance, to distinguish stocks of fish species that migrate from different spawning areas. This has important management and political implications in cases such as the salmon industry, since both the political units that include spawning locations and those where the fish are harvested have an economic interest in the stocks. In forestry, nurseries where genetically superior stocks of conifers are developed and grown are subject to genetic "contamination" by airborne pollen from wild trees. Methods developed in population genetics are useful for determining the distance that pollen travels, and for measuring levels of contamination, which affects the stock's market value. Evolutionary geneticists have also been active in analyzing the genetic basis for desirable traits in conifers such as growth rate and insect resistance. Such knowledge contributes to hybrid breeding and genetic engineering programs. [VIII-C] FINDING USEFUL NATURAL RESOURCES [VIII-C1] Organisms past and present are the source of innumerable natural resources. The most conspicuous fossil resources are fossil fuels, in discovering which paleontology plays an indispensable role. For all but the youngest part of the geological record, fossils are the least expensive and most precise means of making age correlations among sedimentary deposits. These correlations are an integral part of the search for, and the tracing of, concentrations of oil, natural gas, coal, and other economically important deposits. [VIII-C2] Living species include vast numbers that may prove useful as future crops or, especially, as resources or natural products that could be developed for medical, nutritional, industrial, or research applications. Over 20,000 different plant names are listed by the World Health Organization as having been used for medicinal purposes by human populations, and undoubtedly a substantial fraction of these really are effective. For example, malaria was treated until very recently by quinine, from the cinchona tree. Recent examples of medicinally useful plant compounds abound. Taxol, a compound in Pacific yew, has shown promise in the treatment of breast cancer; the rosy periwinkle of Madagacar proved to have two chemicals that have been useful for fighting leukemia, and which have increased childhood leukemia survival rates from 10% to 95%. Diverse natural plant products are also used as scents, emulsifiers, and food additives in industrial applications. Modern molecular biology and biotechnology rely on the polymerase chain reaction, based on an enzyme, stable at high temperatures, extracted from bacteria that inhabit thermal springs. Pharmaceutical and other industries have initiated screening programs of natural products in the expectation of more such discoveries. [SIDEBAR ON EPIBATIDINE FROM FROGS - HANKEN] [VIII-C3] Exploration of biological diversity for new natural products was a major emphasis of the National Research Council's report, "A Biological Survey for the Nation", and of the Systematics Agenda 2000, a report on the critical importance of research and training in systematics. Two areas of evolutionary biology are germane, indeed indispensable, for targeted exploration. Systematics provides the inventory of organisms, and especially their phylogenetic relationships, that is essential for organizing and, in part, predicting the characteristics of organisms. Evolutionary ecology in the broad sense - the analysis of adaptations - points us toward organisms whose adaptive requirements are likely to include features that we might use. For example, it was correctly predicted that hot-springs bacteria would have a heat-stable DNA polymerase; neurobiologists seeking inhibitors of neurotransmitters for research purposes were led naturally, and successfully, to the venoms of certain snakes and spiders, organisms that have evolved just such inhibitors to overcome their prey. Fungi release antibiotics to control bacterial competitors, and plants harbor many thousands of compounds to ward off natural enemies. Evolutionary-ecological study of these adaptations has only begun to reveal compounds that will repay further study. [VIII-D] ENVIRONMENT AND CONSERVATION [VIII-D1] Evolutionary studies have paved the way for some methods of remediation and restoration of degraded land. For example, extensive studies have described the systematics, genetics, and physiology of some grasses and other plants that have adapted to soils highly polluted with nickel and other toxic heavy metals. These studies have laid the foundation for revegetating and stabilizing soils made barren by mining activities, or even detoxifying metal-contaminated soil and water. For instance, some bacteria have the capacity to metabolize mercury to a less toxic form, and their genes for this capacity have been transferred into plants in laboratory experiments. [NY TIMES Apr. 16, 1996 GIVES REF.] Likewise, studies in the evolutionary ecology of seed dispersal, germination, and heat tolerance play a role in reforestation of overgrazed land in tropical America and elsewhere. [DOCUMENT?] [VIII-D2] Concern about environmental impacts of human activity ranges from the prospect of global warming to the projected and already documented extinction of species. Paleobiological studies of past changes in climate, sea level, and species' distributions provide some insight into the kinds of organisms that are most likely to be adversely affected by global warming - namely, those that have low dispersal powers, narrow geographic ranges, and narrow ecological tolerances. The fossil record of the most recent ice ages provides a detailed picture of how species and ecological communities have responded to cycles of global warming and cooling, both on land and in the sea. Such information can be a source of insight into how species may respond to future climate changes. [VIII-D3] Due to human activity, genetically unique species and populations are becoming extinct at an alarming rate. Evolutionary biology plays a major role in addressing this "biodiversity crisis." An important consideration is which species, ecological communities, or geographic regions need the most urgent conservation efforts, since there are economic, political, and informational limits on which species to save: designating areas for preservation requires funds, political compromise, awareness of legitimate competing social needs, and far more information on biological diversity than is known. [VIII-D4] Among the conservation roles of evolutionary biology are: (1) Using phylogenetic information to determine which regions contain the greatest variety of biologically different, unique species (e.g., the three species of anteaters are more different from other mammals, and from each other, than say, three species of deer mice); (2) Using the data and methods of evolutionary biogeography (the study of organisms' distributions) to identify "hot spots" - regions with high numbers of geographically localized species (Madagascar, New Guinea, and the Apalachicola region of Florida and Alabama are examples); (3) Using genetic and other methods for distinguishing species and genetically unique populations (e.g., the highly endangered, genetically unique Kemp's ridley sea turtle, now the subject of a major preservation effort) [AVISE BOOK]; (4) Using the genetic theory of inbreeding to estimate the minimal population size that will retain enough genetic variation to prevent inbreeding depression and maintain the ability to adapt to diseases and other threats; (5) Using the theory of life histories and other characteristics to predict which species are most vulnerable to extinction; and (6) Using genetic markers to control traffic in endangered species. (These methods have been used to spot illegal whaling, and are routinely used to distinguish illegally smuggled from legal, captive-bred parrots. In fact, these birds have such a high market value that insurance companies are requiring, and owners are obtaining, DNA fingerprints of pet parrots.) [VIII-E] APPLICATIONS BEYOND BIOLOGY [VIII-E1] Just as evolutionary biology and other biological disciplines have furthered each others' goals, so there are reciprocal benefits between evolutionary biology and nonbiological science and technology. Perhaps the oldest such relationship is with economic theory. Darwin's idea of natural selection was inspired by reading the works of the economist Thomas Malthus, who stressed the effects of competition for scarce resources. In this century, development of several evolutionary topics, such as the evolution of life histories and foraging behavior, borrowed from economic theory. But ideas have flowed in the other direction also. The influence of population genetics on economics began with Sewall Wright's work on path analysis, a statistical technique developed to analyze complex causal systems such as the effects of heredity and environment on phenotypes. This method is now widely used for causal analysis in economics and sociology. More recently, some economists have adopted one of the central principles of evolutionary theory, given mathematical form again by Wright, namely the effects of historical contingency on subsequent change. Economists such as Douglas North have applied this principle, indicating a shift away from economic theory based on the classical notion that individuals know what it takes to maximize benefits and minimize costs. [VIII-E2] We have already referred to the central role played by evolutionary geneticists in the development of analysis of variance and other statistical techniques. Moreover, the need for mathematical tools to solve theoretical and practical problems in evolution has stimulated developments in mathematics as such. In analyzing random effects in evolution (genetic drift), Wright used diffusion equations that inspired further work on random processes by mathematicians such as William Feller, who was led to develop a large branch of probability theory. More recently, analysis of phylogenetic trees has inspired mathematical research. There is no analytical solution to the problem of which possible phylogenetic tree, out of the many thousands that could describe the relationships among a few dozen species, best fits the data. This challenge has attracted mathematicians and especially computer scientists to the problems of developing algorithms for solving complex problems that require efficiently sorting through myriad possibilities. These methods, suitably modified, will have wide application outside evolutionary biology. [VIII-E3] Evolutionary computation and artificial intelligence are among the most active, and potentially useful, subjects in computer science today, and are based directly on evolutionary theory. The famous computer scientist John Holland [REF: 1975,1992] was profoundly influenced by his colleagues in evolutionary biology, and with his students, has pioneered evolutionary computation and genetic algorithms for numerical problem solving. The instructions, parameters, and variables in a computer program function together to perform operations whose efficiency can be evaluated by some criterion that is analogous to Darwinian reproductive fitness. Computer programs are allowed to evolve toward greater efficiency by processes that mimic organic evolution: elements in the program are "mutated" and "recombined" at random, and then generate "offspring" instructions and variables. The performance of the "offspring" is evaluated, and the best are retained (as in natural selection) for repetition of the process. Thus the program evolves toward greater efficacy. Variants of this process include analogues of other evolutionary processes as well. This is such an active field that two new journals - Evolutionary Computation and Adaptive Behavior - include many papers on how biological concepts may be applied to computer science and engineering. [VIII-F] UNDERSTANDING HUMANITY [VIII-F1] Evolutionary data and methods have been used to address many questions about the human species - our history, our variability, our behavior and culture, and indeed, what it means to be human. Some studies on human variation and evolution are unambiguous and uncontroversial. Other writings about human evolution and its social implications, by anthropologists, geneticists, evolutionary biologists, and persons untrained in biology, have been extremely controversial - and can evoke as much disagreement among evolutionary biologists as elsewhere. These are usually topics in which the data are insufficient to support the claims or instances in which scientific data have been used, without justification, to support social or ethical arguments. Moreover, popular writers often misinterpret human evolution and genetics - indicating the need for broader education in these subjects. [VIII-F2] Human History. The salient points here, referred to earlier in the document, are our incontrovertible relationships to African apes, the history of hominid evolution as studied in the fossil record, and the history of modern human populations, in which evolutionary genetics has played the leading role. We have seen, for example, that all modern populations, and the differences among them, probably originated from a single, relatively small ancestral population within the last 800,000 years. Extensive population genetic studies, coupled with phylogenetic methods, have also determined genealogical relationships among human populations [FIGURE: DENDROGRAM OF HUMAN POPS]. The genetic relationships correspond quite well to relationships among language groups, which linguists have elucidated with methods modified from evolutionary biology. The combination of these disciplines has provided a sounder basis for speculation about major population migrations and the spread of important cultural systems such as agriculture and the use of horses and other domesticated species. [VIII-F3] Variation within and among populations. As we noted earlier, genetic differences among human populations are trivial compared to the great amount of variation within populations. Moreover, the geographic pattern of alleles is frequently very different at different loci, which implies that a difference between populations in one characteristic is not likely to be useful for predicting differences in other characteristics. These data and principles have supported the vigorous arguments that many evolutionary biologists - as well as others - have made against racism and other kinds of stereotyping [CITE DOBZHANSKY, OTHER] [VIII-F4] In a similar vein, evolutionary biologists have been vocal in arguments about whether differences in IQ and other behavioral traits within and among populations are genetically determined and immutable. Advocates of genetic determinism have influenced social policy in some societies, for example by educational "tracking" based on youths' IQ scores, and have suggested policies based on the supposition that economic and racial classes differ genetically in IQ. Evolutionary geneticists have repeatedly pointed out that the fact, known to every geneticist and evolutionary biologist, that even if a trait shows high heritability, it often nonetheless can be greatly altered by environmental conditions (such as economic circumstances and education), and is therefore not immutable. They have also been among the chief watchdogs for the quality of data on inheritance of IQ and other behavioral traits, pointing out that many such data have been inadequate, in part because controlled experiments are difficult or impossible in human populations. Evolutionary biologists are perhaps particularly sensitive to these issues because of a previous history in which genetics and evolutionary theory have been misappropriated to justify injustice and cruelty. [VIII-F5] Human Nature. One of the most controversial of all subjects is what may be "natural" to the human species. It also evokes enormous interest, among people in all walks of life, whatever their beliefs about evolution may be. Compared to other species, it is evidently "natural" for us to learn and use language, for example. The issue comes down to which human behaviors may be "instincts," products of our evolutionary history, and which are products of our cultural and family environment. A major field of behavioral evolution, including studies sometimes termed sociobiology, has documented evolved differences in many behavioral traits among other animal species, and has successfully used principles such as kin selection to explain how these characteristics are adaptive. Among evolutionary biologists, anthropologists, and psychologists, many are optimistic that such principles can be applied to human behavior, and have offered evolutionary explanations for many intriguing behaviors that are widely distributed among populations, such as incest taboos and gender roles. Other evolutionary biologists, anthropologists, and psychologists, cognizant of the important effects of learning and culture, are skeptical of these interpretations. For example, the incest taboo, almost as universal as any human pattern that exists, is interpreted by some as an instinct -- an adaptation to avoid the deleterious genetic effects of inbreeding -- and by others as a cultural invention to foster alliances and economic gain. These topics are fascinating and well warrant exploration, but the challenge is to devise definitive tests of the hypotheses, whether biological or cultural. [VIII-F6] Origins of language and cognition. [PASSAGE ON EVOLUTIONARY PSYCHOLOGY, COMPARATIVE STUDIES? REAL? BROCKMANN?] [VIII-F7] Models of cultural change. Analogies between cultural change and biological evolution have been drawn, and have at times influenced models in cultural anthropology. Some past analogies were naive and erroneous, such as the supposition that complexity necessarily increases in both biological and cultural evolution. Even the best such analogies have severe limitations, because some mechanisms of cultural "evolution" differ importantly from those of biological evolution. For example, cultural innovations acquired during a person's lifetime may be transmitted to the next generation -- a kind of Lamarckian rather than Darwinian "evolutionary" change. Also, cultural innovations, ranging from new pronunciations to new tools, spread laterally within generations as well as vertically between generations. Nevertheless, the form and content of evolutionary models can be and has been used, with suitably careful modifications, to develop models of cultural change. [REFS? FELDMAN AND CAVALLI-SFORZA] Some of these models take into account the interplay between cultural and genetic change, since there is some evidence that each can influence the other. The most promising models are quite recent, and have not yet been adequately tested with data. [VIII-F8] Evolution in popular and intellectual culture. No one, from the most dedicated biologist to the most impassioned creationist, would deny that the idea of evolution is one of the most influential in modern thought. Innumerable books have been written about the impact of Darwinism on philosophy, anthropology, psychology, literature, and political history. Evolution has been used (abused, we would say) to justify both communism and capitalism, both racism and egalitarianism. Just as "the devil can cite Scripture to his purpose", Darwinism has been appropriated to support the most disparate of world views, from the "scientific" racism of the Nazis to the mystical evolutionary theory of the Jesuit Teilhard de Chardin. Such is the grip of the evolutionary concept on the imagination. [VIII-F9] Almost all evolutionary biologists would agree, as do almost all philosophers, that neither evolutionary science nor any other science can provide a valid foundation for ethics or the codes of behavior necessary for society. Science may succeed in describing what is and how it came to be that way, but it cannot decide what should be, nor what future we ought to strive for. That is not to say, though, that science lacks implications for philosophy. Although science cannot inform ethical philosophy, since its inception - since Newton and before - it has deeply affected epistemology (the analysis of how we can know what we think we know) and many other philosophical subjects. Evolutionary science, having provided for living systems the material explanations similar to those physics provided for nonliving systems, has influenced philosophy as profoundly as did physics. Indeed, the philosophy of biology, a subdiscipline of the philosophy of science, concerns itself more with evolutionary theory than with any other subject in biology. [VIII-F10] Fascination with evolution, though, is not limited to ethereal realms of intellectual discourse. An unmeasured but probably large economic benefit flows from evolutionary biology, in educating children and adults in scientific concepts and also in providing interesting entertainment. Books and television productions on biodiversity, natural history, human origins, and prehistoric life, including dinosaurs, are extremely popular, and provide a readily understood entry into abstract scientific thinking. Many children become interested in science, engineering, and environmental affairs first through exposure to natural history and then through introduction to the evolutionary principles that explain life's unity and diversity. Even among people who do not pursue careers in science and engineering, interest in natural history and evolution enhances critical thought (the basis of the Jeffersonian ideal of an educated citizenry) and is a considerable economic force, through purchase of books and magazines, toys for children, and attendance at museums and even the cinema. (The popular movie Jurassic Park could not have been made without the new understanding of dinosaurs developed by evolutionary biologists in the preceding 15 years.) The throngs of visitors to the dinosaur exhibits in museums, the popularity of science fiction that employs evolutionary themes, the news coverage of every major hominid fossil and every major new idea about human evolution, the widespread concern about the genetic theories of human behavior, and the prospect (far off, if ever) that we may some day control human evolution - all attest to the fascination, foreboding, and hope that people feel about the evolutionary history and future of humanity and the world. IX CHALLENGES AND OPPORTUNITIES IN EVOLUTIONARY RESEARCH [IX-A] A. Challenges and opportunities: Basic research [IX-A1] Evolutionary research is progressing on many fronts, but as in most areas of science, the unknown still greatly exceeds the known. In some areas we simply have less information than we should. (For example, the history of diversity in the fossil record is very incompletely known.) In other cases, questions have been answered using one or a few study systems, but we do not know how widely the answers can be generalized. (For example, the numbers of genes contributing to reproductive isolation between species has been described for some Drosophila species, but for few other kinds of organisms.) In many cases, evidence has been obtained for or against one of several competing hypotheses, but the full range of hypotheses has not been tested adequately. (Of the many hypotheses that purport to explain sexual reproduction, preliminary tests of only a few have been published.) Some long-standing questions have resisted analysis until recently, but new techniques offer great promise. (Understanding how developmental pathways evolve is a conspicuous example.) Especially in molecular biology, entirely new phenomena have been discovered, such as the homogeneous DNA sequences of the members of multigene families, that call for evolutionary explanation and understanding. [IX-A2] Assuming adequate research support and training of young researchers, we anticipate virtually unprecedented progress in basic evolutionary biology in the next decade or two. In this section, we list some of the areas in which progress is especially desirable and feasible, given present techniques and technical advances that may be anticipated in the near future. Although many evolutionary biologists would undoubtedly add to it, the following list of high-priority questions and challenges represents a consensus of evolutionary biologists with diverse specialties and approaches. We group research questions into several categories, which are equal in importance and priority. [IX-A3] 1. Theory and technique Much of evolutionary research, from genetic mechanisms to phylogeny, has been guided by theory (often, but not always, mathematical), which frames hypotheses, provides predictions or expectations, constrains the interpretation of data, and often specifies the kind of data required to test hypotheses. Training of evolutionary theoreticians continues to be highly important. Among the many areas requiring further theoretical work are: [IX-A3a] a. Further development of coalescent theory, for inferring evolutionary processes from "gene trees", i.e. phylogenies of DNA sequences. [IX-A3b] b. Developing the theory of the relationship between phylogenies of genes and phylogenies of species and populations. [IX-A3c] c. Further theoretical work on phylogenetic trees, e.g., methods to compare and evaluate trees, to find trees that best meet optimization criteria, to infer the history of character evolution from the phylogenetic distribution of characters, and to infer evolutionary processes from tree structure. [IX-A3d] d. Population genetic theory for underexplored topics, such as the nature and evolutionary consequences of gene interactions and the evolution of polygenic traits with different genetic architectures. [IX-A4] All research depends on advances in techniques.. Molecular and other experimental methods greatly influence evolutionary research, but evolutionary biology is also, and perhaps peculiarly, dependent on analytical, statistical and numerical (computational) methods. In the future, evolutionary research will particularly require progress in 1. Methods for searching and manipulating massive amounts of data, especially DNA sequences. 2. Improved methods of maximum likelihood and other statistical procedures for analyzing population-genetic data (e.g., molecular markers of mating systems). 3. Methods of aligning DNA sequences. 4. Improved methods of phylogenetic analysis (as noted above). 5. Improved methods for fine-scale mapping of quantitative trait loci. [IX-A5] 2. Evolutionary history Describing and explaining the history of evolution is one of the major goals of evolutionary biology. This is achieved mostly by phylogenetic methods (next category) and by paleobiological study. Priority questions in paleobiology include: [IX-A5a] a. A more complete history of the diversity of life through time, especially of protists and other forms of life in the Precambrian. [IX-A5b] b. Improved data and methods for testing hypotheses about the causes of variation (among time periods and taxa) in rates of speciation, extinction, and diversification. (This includes accounting for both mass and background extinctions.) [IX-A5c] c. Explaining differences among taxa in recovery from mass extinction events. [IX-A5d] d. Tracing more fully the history and rate of evolution of characters, and of correlations among characters, in evolving lineages. (Such data are required to test many hypotheses, such as "punctuated equilibria.") [IX-A6] 3. Systematics Systematic studies contribute to our knowledge of evolutionary history, and can test hypotheses about evolutionary process, by (ideally) inferring the sequence and time of branching of lineages and the sequence and rate of change in their characteristics. Improved analytical methods and data (especially molecular data) have recently made this a far more vibrant, rigorous field than it had been, but much remains to be done. Among the important challenges are: [IX-A6a] a. Documenting the diversity of living organisms. Estimates of the number of living species vary widely, and many, if not most, species have not yet been described in groups such as bacteria, protists, fungi, nematodes, mites, and many groups of insects, that play exceedingly important roles in ecosystems and include many forms that directly impinge on human welfare. Eventually, a full inventory of living organisms and their biological characteristics will provide the same kind of foundation for ecology, evolutionary biology, and other biological sciences that geological surveys provide for earth science. [IX-A6b] b. "Growing the tree of life." Estimates of phylogeny have been developed for a small minority of taxa, but even these have already been used extensively for testing hypotheses in many areas of evolutionary biology and ecology. A high priority for evolutionary systematics should be more (and more robust) phylogenies, embracing the full panoply of organisms. These can successively be joined to build a phylogeny of all life - a project already initiated by evolutionary systematists David and Wayne Maddison. [DELETE NAMES?] The more complete the tree, the more it will serve as an organizing framework for biological data of all kinds, and as a basis for testing innumerable hypotheses. In order to accomplish this, data bases for storing phylogenetic estimates will be indispensable. [IX-A6c] c. Methods for inferring, evaluating, and using phylogenies to test hypotheses require improvement. For example, existing statistical methods for assessing the confidence to be placed in a phylogeny are "first-generation" methods, that should ultimately be superseded. Methods for using tree structure to determine differences among groups in rates of diversification are still being developed. [IX-A6d] d. Theoretical and empirical bases for integrating phylogenetic history with evolutionary processes need to be developed. A great gulf exists between theory and data on evolutionary processes (e.g, evolutionary genetics) and the procedures of phylogenetic inference. Indeed, some systematists argue that phylogenetic study should depend as little as possible on evolutionary process theory. Integration of evolutionary biology requires exploration of the ways in which understanding evolutionary process can affect phylogenetic inference. (For example, the theory of gene trees [coalescent theory] has clear, broadly acknowledged, implications for phylogenetic analysis.) Likewise, a few studies have asked how genetic variation and other genetic properties of species have affected the real history of character evolution and diversification (e.g., Bell and Kaufopanou 19XX, Futuyma et al. 1995), but this vast realm of contact between evolutionary history and evolutionary process remains mostly unexplored. [IX-A7] 4. Evolutionary genetics Evolutionary genetics, including population genetics, has long played a major role in the theory and analysis of character evolution and speciation, and continues to do so. Among the major challenges for evolutionary genetics, we include: [IX-A7a] a. More theory on inadequately explored topics, such as the kinds of gene interactions (epistasis) and their evolutionary consequences; genetic processes in metapopulations, consisting of local demes subject to extinction and recolonization; broader exploration of genetic processes leading to speciation. [IX-A7b] b. Explaining levels of genetic variation in natural populations. This old, refractory problem remains important, and shows promise of yielding to new methods such as analysis of DNA sequence variation. [IX-A7c] c. Describing "mutational landscapes," i.e. characterizing the variation that arises by mutation. Whether or not there are "forbidden" character states, whether mutations act synergistically, and what their pleiotropic effects may be, are among the many questions with important implications. [IX-A7d] d. Characterizing the genetic basis of character variation within and among species. Identifying the loci, and their mechanistic effects on development and physiology, will become feasible as methods of QTL mapping (quantitative trait loci) become improved. These methods promise to answer many long-standing questions. [IX-A7e] e. Developing a predictive theory of adaptability and response to environmental change. Global warming and other environmental changes make it imperative that we understand when populations will succeed or fail in adapting to new environments. This will require an understanding of what governs rates of evolution. [IX-A8] 5. Speciation Possibly no major topic in evolutionary biology is as difficult and controversial as speciation, perhaps because it is generally too fast to be fully documented in the fossil record, but too slow to observe within an investigator's lifetime. New approaches are needed, and are on the horizon, for answering some major questions about this process, the fount of biological diversity. [IX-A8a] a. Character differences among newly formed species, especially those that can prevent gene exchange between them, need to be characterized genetically and mechanistically. That is, we need to know not only the number and location of genes (already estimated in a few cases), but also the developmental or biochemical effects by which gene differences cause reproductive isolation and other character differences. [IX-A8b] b. Determine the causes of speciation. Whether selection, genetic drift, or a combination of the two are generally responsible for speciation is a major, unresolved question. If selection is generally the cause, the agents of selection will need to be identified. [IX-A8c] c. Determine the rapidity and predictability of speciation. We know little about how inevitably isolated populations become different species, at what speed, or if the rates depend on taxa or environmental conditions. Related to this, the causes of evident differences in speciation rate among taxa are poorly understood. [IX-A9] 6. Evolution of genes and genomes The intensely active interface between evolutionary biology and molecular genetics will continue to provide insight into the evolution of structure of genes and genomes. New molecular phenomena may well be revealed, that will invite evolutionary interpretation. From the present standpoint, subjects that require further study include: [IX-A9a] a. Further analysis of the evolution of rates of mutation and recombination, both theoretically and empirically. Important questions include whether or not "optimal" rates evolve; what evolutionary processes lead to variation in recombination among and within genomes; and what the mechanisms of such variation may be. [IX-A9b] b. Documentation and assessment of the evolutionary consequences of novel sources of genetic variation, such as lateral transfer among species, transposable elements, and unequal exchange. [IX-A9c] c. Deeper understanding of the evolution of linkage relationships among genes, and of changes in the number and the structure of chromosomes. [IX-A9d] d. Analysis of the roles of selection and other factors in the evolution of coding and noncoding DNA. [IX-A9e] e. Analysis of the evolution of the information content in genomes, from both phylogenetic and mechanistic perspectives, as well as evolutionary analysis of the packaging of information, large-scale patterns (e.g, isochores???) in DNA, and the process whereby new gene functions evolve. [IX-A10] 7. Evolution and development The process by which developmental pathways evolve, and conversely the effects of development on evolutionary trajectories, hold profound interest not only for developmental biologists, but also for paleobiologists, systematists, and all biologists concerned with the evolution of phenotypic characters. Due to molecular and other technical advances in developmental biology, unprecedented progress in this area may be anticipated, and in fact is well under way. Almost every respect of this field will reward study, but several approaches and topics will be especially important: [IX-A10a] a. Theoretical analysis of how phenotypes may be altered or constrained, given data on model developmental pathways. Although models of developmental systems have already played important roles (e.g., Turing; Oster and Alberch), theory in this area has lagged behind that in several other areas of evolutionary biology. [IX-A10b] b. Analysis of the relationships between development and the genetic basis of variation in characters, within and among species. This will require comparative and experimental study of developmental differences among genotypes and among closely related taxa, complementing the broad taxonomic comparisons that are traditional in developmental biology. [IX-A10c] c. Analysis of the molecular and other developmental processes by which genetic differences are translated into phenotypic differences. Closely related to the proceeding point, the analyses will require study of phenomena such as changes in the number, function, and regulation of genes that affect a trait, as well as developmental mechanisms at the level of tissues and organs, such as induction, cell adhesion, cell death, and heterochronic changes in form. [IX-A10d] d. Analysis of the developmental basis of complex and evolutionary novel characters. Possibly no problem in character evolution is as challenging as understanding the mechanisms by which complex characters (e.g., feathers, body plans) have evolved. At present, this is perhaps a long-term goal. [IX-A10e] e. Identifying developmental constraint on evolution, and the mechanisms that underlie them. "Constraint", "burden", and "canalization" are important but almost metaphorical concepts, that describe developmental phenomena thought to underlie the long-term phylogenetic stability (or conservatism) of many characters. Confirming their reality and identifying the underlying mechanisms will have profound implications for understanding rates and modes of evolution. [IX-A10f] f. Understanding the relationships between phylogenetic and biological homology. Phylogenetically homologous characters, i.e. characters possessed by the common ancestor of different taxa, sometimes have remarkably different developmental pathways (Wagner and Müller 19XX). A major challenge for developmental evolutionary biologists will be to understand how the developmental foundation of a character may change even though its mature form remains relatively constant. Conversely, it is important to understand how the developmental roles of conserved genes come to differ among taxa. [IX-A10g] g. Comparison and analysis of developmental mechanisms in modular versus nonmodular patterns of organization. Development in modular organisms such as plants and corals clearly differs from development in nonmodular forms such as arthropods and vertebrates. It will be important to identify the differences and to understand evolutionary transitions between them. [IX-A10h] h. Understanding the evolution of self- and allorecognition systems. Compatibility versus incompatibility of cells, mediated largely by cell-surface factors, governs such phenomena as union of gametes, pollen/stigma interactions (e.g., self-incompatibility) in plants, immune systems, and migration and adhesion of cells in animal development. The concerted attention of evolutionary and developmental biologists to these phenomena will have broad implications for subjects such as speciation, breeding systems (of plants), character evolution, and disease resistance. [IX-A11] 8. Evolution of phenotypic characters The several subdisciplines of evolutionary biology that take specific classes of phenotypic characteristics as their subject will all continue to address important problems, some of which are in only the early stages of analysis. The following sample is not at all exhaustive. [IX-A11a] a. Develop ways to measure and explain the disparity between optimal and real character states. Theoretical work has defined the optima for many kinds of characters, e.g., of behavior and life histories, and some work in these fields has been criticized for supposedly assuming that organisms are optimally adapted. Although many workers do not make this assumption, criteria for determining how far phenotypic characters are from their optima, and why, have not been rigorously developed. Development of criteria may advance the study of adaptations to new levels of rigor and insight. [IX-A11b] b. Account for variation in the rate of evolution among characters and among taxa. The pressing need is to develop methods of distinguishing the relative roles that "external" factors (e.g., ecological sources of selection) and "internal" factors (e.g., genetic correlations, developmental constraints) play in determining evolutionary rates. [IX-A11c] c. Develop and test theories for the evolution of suites of characters that are correlated either by function or by their genetic and developmental foundations. How do we determine which characters will evolve in concert, or how the degree of concert changes over evolutionary time? [IX-A11d] d. Develop and test theories for a large class of interesting characters, such as: -sexual versus asexual reproduction, variations in sex determination, inbreeding versus outcrossing, and other aspects of breading systems; -sexually selected characters; -evolutionary changes in the mechanisms of behavior, including neural substrates and hormonal controls; -evolution of the mechanisms by which organisms respond to varying environments, such as phenotypic plasticity, learning, dispersal, and physiological acclimation; -evolution of physiological tolerances of environmental variables such as temperature, water availability, and environmental and dietary toxins, and the tradeoffs and constraints that may limit breadth of tolerance; -evolution of the breadth of species' diets, habitat use, and geographic distributions, and the factors that limit these properties. [IX-A12] 9. Evolution of ecological interactions and communities About 30 years ago, evolutionary ecologists hoped to explain the features of ecological communities, such as species diversity and food web structure, by developing a theory of interactions among species based on both evolution and demography. Progress toward that goal has been only modest for several reasons, including the complexity of communities and the failure, in the past, to take sufficient account of the effects of evolutionary and geological history. A more informed, pluristic community ecology seems to be emerging (e.g., Ricklefs and Schluter 1993), in which evolutionary history and processes will play essential roles. Among the priority research areas are: [IX-A12a] a. Develop methods for identifying and quantifying the effects of evolutionary and geological history on the composition and dynamic changes in communities. [IX-A12b] b. Develop and test theories of the effects of genetic composition and evolutionary change on the stability of species interactions and on extinction vs. persistence. [IX-A12c] c. Develop and test hypotheses to account for the limits to the ecological and geographic distributions of species (cf. 8d). [IX-A12d] d. Develop methods for distinguishing the effects of coevolution and species assembly on the composition and structure of communities. [IX-A12e] e. Develop and test predictive theories of the coevolution of interacting species, including -host/parasite interactions and the evolution of virulence and resistance in pathogens and their hosts; -mutualistic interactions, especially those involving microbial symbionts, including the stability of mutualisms and their role in community structure; -competition among species: its importance and evolutionary consequences; -diffuse coevolution, i.e. evolutionary dynamics of complex interactions among multiple species (an exceedingly important and little understood problem). [IX-A12f] f. Develop and test theories of the effects of evolution on properties of ecosystems (e.g., productivity, nutrient turnover) and their effects on the physical environment. B. Challenges and opportunities: Applications of Evolutionary Biology to Social Needs [IX-B1] As discussed in Section VIII, evolutionary biology has directly or indirectly made diverse contributions to the social applications of biology. However, the potential contributions greatly exceed those made so far. Compared to some other biological disciplines such as biochemistry and ecology, in which applications to health or environmental science are emphasized in training and research, development of an explicit field of "applied evolutionary biology" is only beginning (e.g., Meagher and Meagher [CITATION FORMAT FOR RUTGERS WORKSHOP?] 1994, Nesse and Williams 19XX, ???, ???). [IX-B2] The history of evolutionary biology shows that benefits between basic and applied research flow in both directions. Evolutionary genetics has profited from, and indeed has overlapped greatly with, quantitative genetics and other genetic research aimed at improving crops and domesticated animals. Studies of mutational changes in the metabolic capacities of microorganisms, pursued in part because of their industrial applications, have shed light on the evolution of biochemical pathways. Genetic and phylogenetic studies of corn and other crops have provided insight into rates of evolution and changes in developmental pathways. Study of sickle-cell hemoglobin and other polymorphisms in humans has provided some of the best analyses of modes of natural selection. The evolution of pesticide and drug resistance in insect pests, weeds, rats, and pathogenic bacteria, the evolution of life-history characteristics in overexploited fish populations and in introduced insect pests, the evolution of virulence in viruses and bacteria, and the coevolution between insects and plants have been subjects of some of the best studies of evolutionary dynamics. Phylogenetic studies of relationships among human populations, and of relationships between humans and other primates, have provided some of the most insightful analyses of evolutionary history. [IX-B3] This background shows that evolutionary biologists can often address basic questions by working on systems that are directly relevant to societal needs, as well as, if not better than, if they use species or systems that have less immediate relevance. To be sure, the ideal systems for addressing certain basic intellectual problems will often not be those with immediate social utility. Moreover, we reiterate the importance of exploring and understanding the diversity of organisms as an intellectual goal, even if its utility is not immediately evident. But in many cases, the choice of a socially relevant organism or system will both advance basic research and contribute to societal needs. We anticipate that evolutionary biologists will increasingly play these dual roles. [IX-B4] It is important to emphasize that much of the progress in applied evolutionary biology will require and be inseparable from progress in basic research. As in other biological disciplines, studies of model organisms and systems (including not only standard lab species such as yeast, Drosophila, and Arabidopsis, but also a variety of wild species) will provide insights that can be applied to societal needs. Likewise, conceptual and theoretical advances will contribute to progress in both basic and applied evolutionary biology. Within the next decade or two, important progress in the contributions of evolutionary biology to societal needs will be made in the areas of health science, agricultural and other biological resources, natural products, environment and conservation, technology development, and educational and intellectual interchange with other scholarly disciplines and with the general public. Some important subjects of inquiry follow. [IX-B5] 1. Health Sciences Advances in applying evolutionary disciplines to human health will flow from studies of human diversity and of the biology of disease organisms and their vectors. These advances fall under several headings. [IX-B5a] a. Human genetic diversity. The Human Genome Diversity Project (HGDP) complements the Human Genome Project, which ultimately will sequence the entire human genome. The HGDP will provide data, at the molecular level, on the immense genetic diversity that exists within and among human populations. Population genetics is the evolutionary discipline that provides analytical tools for describing genetic diversity, inferring its causes, and predicting and testing its effects. The techniques of population genetics and phylogenetic analysis will use the mounting information on human genetic variation to determine the history of populations (e.g., past sizes, movements, and interchange). Evolutionary genetics will continue to provide tools for identifying the genetic lesions associated with inherited diseases and defects (as in the case of cystic fibrosis, breast cancer, and others). Evolutionary comparisons of human DNA sequences with those of other species will provide insight into gene functions. Population geneticists will analyze the genetic basis of interesting variable traits, such as reactions to allergens. Genes that provide adaptation to environmental factors such as pathogens and diet will be identified by studying genetic differences among and within populations. The methods used by evolutionary geneticists will be applied to human diversity in order to elucidate cases of complex inheritance of disease (e.g., those due to interactions among multiple genes) and to study genotype-environment interactions: the differential expression of traits such as disease resistance under different environmental conditions. [IX-B5b] b. Genetic diagnosis [NB: NEED BETTER DEFINITIONS/EXPLANATION OF GENETIC DIAGNOSTICS] Population genetics has developed, and is continuing to improve, analytical methods for identifying individuals and relationships among individuals from their profile of genetically variable markers. This methodology also uses linked markers to determine the likelihood that an individual carries genes of particular interest (e.g., those causing genetic disease). As evolutionary geneticists improve these methods and apply them to data on human genetic diversity, it will be possible to use molecular markers more confidently for such purposes as (1) counseling individuals on the likelihood that they or their children will carry a genetic disease, (2) determining paternity, and (3) forensic applications. [IX-B5c] c. Developmental genetics. Comparative data on the genetic and mechanical bases of development in diverse vertebrates and other organisms will elucidate the mechanisms of human development. (See box on HOX genes.) Such studies will contribute to understanding the bases of hereditary and other congenital defects in humans, and may ultimately be useful in developing gene therapies. [IX-B5d] d. Mechanisms and evolution of antibiotic resistance. Genetic, phylogenetic, and comparative biochemical studies of viruses, bacteria, fungi, helminths (parasitic worms), and other parasites will contribute to identifying targets for antibiotics. The rapid evolution of antibiotic resistance in previously susceptible pathogens presents a critical need for evolutionary study, aimed at understanding the mechanisms of resistance, factors that may limit resistance, its rate of evolution, and ways to prevent or counteract such evolution. [IX-B5e] e. Parasite virulence and host resistance. Evolutionary studies of parasite/host interactions, including both model systems and human parasites and pathogens, are only beginning to determine the conditions that lead parasites to become more virulent versus benign. Evolutionary geneticists and evolutionary ecologists need to develop a general, predictive theory of the evolution and population dynamics of pathogens and their hosts, especially for rapidly evolving organisms such as H.I.V. Analyses of genetic variation in resistance to pathogens in humans and other hosts are also needed. [IX-B5f] f. Epidemiology and evolutionary ecology of pathogens and parasites. New and resurgent diseases have emerged as major threats to public health, and more will probably emerge in the future. Evolutionary biologists can make major contributions of several kinds. Screening for and studying the phylogeny of organisms related to known pathogens (e.g., viruses of other primates and vertebrates) may identify potential pathogens, should they enter the human population. Genetic, ecological, and phylogenetic study of new and emergent pathogens that are already known (e.g., hantavirus, the Lyme disease spirochaete, etc.) can elucidate their origin, rates and modes of transmission, and ecological circumstances leading to outbreaks or to the evolution of greater virulence. Experimental study of model systems, including organisms related to known pathogens, can identify mechanisms of virulence and the genetic and environmental factors that influence resistance. [IX-B6] 2. Agriculture and biological resources Section VIIIB noted the many ways in which evolutionary biology has had an intimate relationship to agriculture and to managing biological resources such as forests and fisheries. The scope for further contributions is enormous. We highlight only a few of the most important subjects to be pursued. [IX-B6a] a. Pesticide resistance. Despite alternative methods of pest management, judicious use of pesticides will undoubtedly remain indispensable. The evolution of pesticide resistance in insects, nematodes, fungi, and weeds is a major economic problem that should receive major attention. This will require studies of the genetics and physiological mechanisms of resistance, population dynamic studies, and modeling of methods to limit or delay evolution. [IX-B6b] b. Alternatives in pest management. Evolutionary considerations are important in evaluating many alternative methods of pest management, such as mixing (intercropping) different crops or crop varieties, or developing transgenic crops that carry resistance factors against insects or other pests. For example experiments have shown that tobacco pests can adapt to transgenic tobacco carrying a bacterial toxin, highlighting the need for studies of genetic variation in insect responses to transgenic crops. A large field of evolutionary ecology concerned with plant compounds and the interactions between plants and their insect and fungal enemies is relevant. There exists enormous potential for transgenic use of the innumerable secondary compounds and other properties of wild plants that protect them against the majority of insects and pathogens. Experimental and phylogenetic screening of these properties will prove rewarding. Complementing the search for natural resistance factors, it will be important to analyze their physiological effects on pest organisms, the mechanisms by which some insects and fungi overcome these effects, and genetic variation in responses of target species to natural resistance factors. [IX-B6c] c. Genetic diversity in economically important organisms. The production of food, fiber, and forest products has historically been greatly improved by exploiting genetic variation, and the methods for doing so have been deeply informed by evolutionary biology. Evolutionary and agricultural scientists together will use QTL (quantitative trait loci) mapping and other methods to locate genes and elucidate the mechanistic bases of important plant traits, such as resistance to pathogens and to stresses such as water deficit. Such studies will also serve the interests of basic scientists interested in the adaptations of plants to these environmental factors. Similar studies on wild plants will locate genes or useful traits that may be genetically engineered into crops. Research programs of this kind will use principles and information from studies of plant phylogeny and adaptation. The critically important task of developing and maintaining germ plasm banks - i.e., storing genetic diversity of crops for future needs - will rest, as it has, on studies of variation within and among populations. [IX-B6d] d. Fisheries. Several kinds of evolutionary studies have been and will continue to be important in managing commercial and sport fisheries. Further development of molecular markers will continue to distinguish breeding populations and migration routes of species such as cod and salmon. Studying the evolution of life history characteristics such as growth rate and age at maturity will enable managers to evaluate the genetic and demographic effects of harvesting. For certain trout species and other that are widely stocked, genetic and physiological studies of adaptation and fitness in different environments will be useful. Such studies will also include transgenic fish, which are in the early stages of development. [IX-B7] 3. Natural Products and Processes Almost all pharmaceutical products, many household products, and many industrial applications (starting historically with the manufacture of bread and wine) either use living organisms or originated from biological processes in organisms. Pharmaceutical and other industries are actively searching for novel products and processes, by screening plants, animals, and microorganisms (Meagher and Meagher 1994). Plants and animals have been used mostly as sources of useful products. Microorganisms provide not only products, but biochemical processes useful in biosyntheses (e.g., antibiotics, solvents, vitamins, and also biopolymers), biodegradations (e.g., in toxic waste sites), and biotransformations (to desired steroids, chiral compounds, and others). Because of its commercial implications, searching for and developing novel products and processes raise serious issues in patent law, international law, and publication of scientific data, which are beyond the scope of this report, but which will affect the engagement and activities of research scientists. Evolutionary studies will greatly contribute to research and development of novel products and processes: [IX-B7a] a. Systematics and phylogeny play an indispensable role. Documenting the diversity of potentially useful organisms is the foundation for further work. This has been recognized, for example, by Merck and other companies that have funded biodiversity inventorying in Costa Rica and elsewhere. The phylogenetic aspect of systematics is crucial for pointing toward species that are related to those in which potentially useful compounds or metabolic pathways have been found, for related species may have similar, perhaps more efficacious, properties. The systematics of bacteria, fungi, and other inconspicuous organisms are very poorly known, and require extensive investigation. [IX-B7b] b. Studies of adaptation can also point the way toward useful properties. Antibiotics, resistance factors for transgenic crops, and other useful products are likely to be found by studying the chemical mechanisms of competition among fungi and microorganisms, the defenses of plants against their natural enemies, and the waxes, steroids, terpenes, hormones, and innumerable other compounds that organisms use for diverse adaptive ends. [IX-B7c] c. Genetic and physiological studies. Bacteria, yeast, and other microorganisms have exceedingly diverse metabolic capacities. They have been the source of penicillin, Taq polymerase (used in PCR, the basis of DNA sequencing), and important industrial processes of fermentation, biosynthesis, and biodegradation. Industry expects that "great advances in bio-processing can be expected from future exploration of the yet unexplored biodiversity of the land and sea" (A. Laskin, in Meagher and Meagher 1994), yet most microorganisms have not yet been described and characterized, the physiological capacities of most of them are unknown, and there is little information on their genetic diversity or on what kinds of novel metabolic capacities can arise by mutation. Researchers trained in evolutionary genetics, physiology, and systematics will make important contributions in this area. [IX-B8] 4. Environment and Conservation Evolutionary principles are immediately applicable to the conservation of rare and endangered species and ecosystems; in fact, many leading conservation biologists have done research in basic evolutionary biology. It is less obvious, but equally true, that evolutionary biology can inform environmental management studies that bear directly on human health and welfare. We highlight only a few of the needs for evolutionary study in environmental management and conservation. [IX-B8a] a. Bioremediation. Bioremediation refers primarily to the use of organisms in ameliorating environmental contamination, such as that due to oil spills and to organic or inorganic toxins in soil and water. In the broad sense, it also includes sludge treatment and restoration of degraded soils; Bacteria and other microorganisms are the major players in bioremediation; both naturally occurring and introduced microorganisms with desired capabilities are used. Some plants extract heavy metals from soil and can be harvested; also, some plants can metabolize certain metals (e.g., mercury) into less toxic forms. [NEED REF: RECENT SCIENCE? OR ARTICLE IN NY TIMES] Plants that are capable of growth in metal-contaminated soils, or in nutrient-poor soils such as those degraded by strip-mining or overuse, are useful in restoring landscapes. [REF?] [IX-B8a2] Evolutionary biology can contribute to bioremediation by identifying species or genetic strains with desirable properties, by understanding the agents of natural selection that give rise to such properties, and by identifying the conditions that favor persistence of useful organisms. For example, oil-degrading bacteria increase in areas suffering oil spills, but their growth is limited by the availability of usable nitrogen and phosphorus, which are absent in oil. Bacteria are known that degrade polychlorinated biphenyls (PCBs) and other long-persistant contaminants, but it is not known if this is a characteristic capability of certain species, or evolves in situ due to selection of new mutations. The community of bacteria involved in waste-water treatment undergoes a change in composition, but the roles of turnover of species versus genetic change in the metabolism of persistent species are not known. Evolutionary genetics and systematics, together with microbial ecology and physiology, should make important contributions to these and other questions in bioremediation. [IX-B8b] b. Unplanned introductions. Many of the most serious pests, including weeds, insects, zebra mussels, and many others, are pests chiefly in regions to which they are not native. The great majority of such introductions are accidental. Quarantine procedures instituted by the U.S. Department of Agriculture are intended to prevent such introductions, insofar as possible. The advent of genetic engineering has caused concern about the escape of vigorous, genetically novel microorganisms, plants, fishes, or other organisms, and about the possibility that genes for novel capacities will spread by hybridization from transgenic organisms into wild microorganisms or plants, transforming benign species into novel pests. Evolutionary biologists have been active in assessing such risks (e.g., Regal 1994 [CITED IN MEAGHER AND MEAGHER]). Studies of gene flow between and within species and evaluation of the fitness effects of genes must complement ecological studies of the relevant organisms in judging the possible unintended effects of transgenic releases. The traditional role of systematics in identifying introduced organisms will continue to play a vital role. [IX-B8c] c. Predicting effects of environmental change. Of the many effects human activities have on the environment, the most sweeping potential effect is global warming. Many other environmental alterations have more local but still profound effects on both wild species and biological resources, such as desertification, salinization of fresh water, and acid rain. Predicting and possibly forestalling the impact of such changes on biological populations is an important goal for ecological studies, but evolutionary biology also faces a major challenge. In particular, we need to understand far better the conditions under which populations adapt to environmental changes versus becoming extinct, and what kinds of species will follow either course. Evolutionary biologists have documented many examples of species which have adapted rapidly, and many which have not, but a fuller theory of vulnerability versus potential for rapid adaptation is needed (Kareiva et al. 1993). Paleobiological studies can complement genetic and ecological studies, by providing detailed histories of changes in the composition of communities and the distribution of species under past environmental changes, and so can develop generalizations about the kinds of species and communities that are most vulnerable. [IX-B8d] d. Conservation of biodiversity. Among both scientists and nonscientists, there is widespread recognition that alteration of habitats, intentional and unintentional harvesting of natural populations, and other human activities constitute a grave threat of widespread extinctions. Habitat alteration, especially, threatens not only conspicuous species such as large mammals and sea turtles, but also innumerable plants, arthropods, and other less known organisms that collectively are a potential source of natural products, pest control agents, and other useful services. Much of the effort in conservation is directed at safeguarding portions of natural ecosystems, so as to conserve multiple species as well as natural interactions and processes. Inevitably, difficult choices will be necessary in allocating resources and educational and political efforts, and not all threatened species and ecosystem will be safeguarded. [IX-B8d2] Evolutionary biology and ecology work inseparably in addressing these issues. Evolutionary systematics plays a crucial role, by providing not only the basic taxonomy that all inventories of biodiversity require, but also information on the evolutionary and biological uniqueness of organisms. The same principles which suggest that the unique giant panda merits more urgent effort than one of the dozens of species of Asian rats may provide broader guidelines on which efforts will conserve the greatest genetic diversity. Information on biogeography (the geographic distribution of organisms) has long been an integral part of evolutionary systematics, and is indispensable to targeting conservation efforts. Thus, we see a major need for intense efforts in describing the diversity, distribution, and ecological requirements of organisms, especially in regions where natural habitats are most rapidly being lost. [IX-B8d3] Evolutionary biologists also study such relevant problems as the minimal population sizes necessary for species to retain enough genetic variation to adapt to diseases and other perturbations; the factors that cause extinction; the role of multiple populations of species in their long-term genetic and ecological dynamics; the role of interactions among species in maintaining viable populations; and the effects of coevolution among interacting species on dynamic processes in ecosystems. Conservation biology will be strengthened by further research on these poorly understood problems. [IX-B8d4] Some conservation efforts rely on germ plasm banks (for plants) and captive propagation. Although relatively few species will be preserved by these means, population genetic theory plays a crucial role in those instances, because small captive populations can suffer from inbreeding. Inbreeding depression has been avoided by applying population genetic principles [CITE TEMPLETON], which will continue to play an important role. [IX-B9] 5. Technology Development In all sciences, the need to solve problems stimulates the development of new techniques and technologies. As noted earlier, most of the broadly applicable technologies that have been developed at least partly from the need to solve evolutionary problems have been in the areas of statistics, computation, and data management. We anticipate that as evolutionary biology addresses ever more complex problems and richer data sets, collaborations among evolutionary biologists will continue to lead to technical innovations in these areas. Some likely areas of progress will be in (a) analysis of the dynamics of complex, nonlinear systems; (b) optimal search routines, e.g., for phylogenetic tree structures; and (c) evolutionary computation, i.e. development of evolving algorithms for efficient problem-solving; and (d) application in artificial intelligence and artificial life. [IX-B10] 6. Public Understanding of Science An important challenge to evolutionary biology lies not in the domain of research, but in the domain of public understanding and appreciation of science, which is necessary both for support of research and for the awareness and understanding an educated citizenry requires in an increasingly scientific and technological age. Many surveys of students and the general public have shown that the United States ranks relatively low among developed nations in their command of science and mathematics. This is a matter of serious concern to all the scientific disciplines, and indeed to all agencies and organizations concerned with the future of the country's human resources for technical and economic development. [IX-B10a] Evolutionary biologists are keenly aware of the need for increased education and understanding of science. The subject matter of evolutionary biology includes topics that directly impinge on individual's health and welfare, such as inherited disease, gene therapy, infectious disease and the evolution of antibiotic resistance by pathogens, food production, agricultural pest management, genetic engineering of crops, bioremediation, conservation, and effects of global warming. Topics related to evolution, such as genetic differences among populations ("races") and indeed the reality of evolution itself, are frequent topics of public discourse. Yet much of the public does not understand basic genetics or evolutionary principles, and a substantial fraction is willing to believe that diseases such as AIDS are punishment administrated by an angry God, rather than evolving organisms that can be combated by scientific knowledge. Incredible as it may seem in an age of spacecraft and supercomputers, more than half of the American public does not even believe in evolution, the unifying principle of all of biology. [IX-B10b] Although some professional biologists have devoted great effort to public education, and the majority of evolutionary biologists teach their subject in universities, the greatest effort in public outreach has been made by organizations such as the National Center for Science Education, and the largest educational role has been played by secondary school teachers. Heightened efforts in teaching about evolution and related subjects are required at both the college and secondary levels. Professional biologists should devote more effort to public education, availing themselves opportunities such as press releases, engagement with the media, and museum exhibits, and should take every opportunity to point out the evolutionary dimension of biological phenomena that capture the public's attention. Pests and disease organisms do not merely "mutate" or "develop" resistance to drugs - they evolve resistance. X. MECHANISMS FOR MEETING CHALLENGES AND OPPORTUNITIES In order to realize the great promise that evolutionary biology holds for both basic and applied science, structural mechanisms, research funding, and educational foundations are required. The following suggestions and recommendations in each of these areas will speed progress toward the basic and applied goals specified in the preceding section. A. STRUCTURAL MECHANISMS [X-A1] 1. Interdisciplinary workshops. Because evolutionary biology encompasses all of biology and has ties to other disciplines such as geology, economics, and anthropology, it is inherently interdisciplinary. Exchange of ideas, information, and techniques is important, both among the subdisciplines of evolutionary biology and between evolutionary biologists and researchers in other biological and nonbiological disciplines. We strongly urge that mechanisms be established to hold annual workshops of an interdisciplinary nature. These would be structured to provide for exchange of ideas and demonstration of techniques, and would be intended to foster research collaborations that might otherwise not develop. We envision bringing together evolutionary biologists with researchers in such fields as developmental biology, neurobiology, endocrinology, microbiology , and many others. Federal or private research laboratories might be suitable sites. [SOMEONE REWORD THIS: I HAVE IN MIND PLACES LIKE WOODS HOLE OR COLD SPRING HARBOR...OR DELETE] [X-A2] 2. Intensive training workshops. Because of the rapid progress in molecular technology, computing, data analysis, and other areas of evolutionary and other biological sciences, researchers can look forward to extended productive careers only be keeping abreast of new developments. We recommend the establishment of annual workshops devoted to rapid, intensive training in new laboratory, computational, and analytical techniques. Although many such techniques will have been developed in other disciplines, the intent of these workshops differs from the explicit development of interdisciplinary research described in the previous item. [X-A3] 3. Training grants for graduate education and research. The health and progress of any discipline depends on training graduate students who will be the next generation of researchers. Both they and the progress of the science are best served by fostering innovative thought and broad perspectives. To this end, we urge the establishment of training grants for graduate student training and research, to foster such perspectives. Basic and applied research will most profit from training grants in (a) interdisciplinary areas, e.g., those bridging evolutionary and traditionally nonevolutionary subjects, and (b) applied evolutionary biology, e.g., applications in health science, agricultural science, natural products and processes, and environmental management and conservation. Training a generation of researchers on the interface between basic and applied evolutionary biology will have the added benefit of exporting evolutionary thinking into some applied disciplines in which the evolutionary perspective is needed. Training grants to institutions with special strength in particular subjects also are valuable, by helping to build centers of excellence and thereby promoting the progress of knowledge. [X-A4] 4. Postdoctoral and mid-career opportunities. Some of the most productive research in biology is performed by postdoctoral researchers and by established researchers in mid-career, when freed from other obligations (e.g., when on sabbatical leaves). Mid-career research leaves are particularly critical for enabling established researchers to learn or develop new techniques or to initiate new research programs, especially those with an interdisciplinary or applied dimension. Support for postdoctoral, and mid-career research positions falls far short of needs. Increasing the sources of such support will be important for progress in both basic and applied evolutionary biology. [X-A5] 5. Enhanced training in underdeveloped subjects. In several important areas of evolutionary biology, the number of young scientists who will be the future corps of researchers is far less than will be adequate. Perhaps the most conspicuous examples are (a) mathematical and statistical evolutionary biology, including modeling and data analysis; and (b) systematics and biology of groups of organisms that have been inadequately studied and/or include species of importance to society (e.g., microorganisms, algae, fungi, plants, insects, nematodes). To address this critical issue, there is a need to train Ph.D. students in these areas and, especially, to open prospects for their employment, such as positions in university and college biology departments. [X-A6] 6. Data bases. Much progress in evolutionary biology depends on analyzing data collected by numerous researchers. For example, data bases of DNA sequences are extensively used not only by molecular, but also by evolutionary biologists. The evolutionary dimension of environmental management, conservation, and exploration of economically useful species will be greatly aided by accessible, widely shared data bases on biodiversity, including information on geographic and ecological distributions, phylogenies, and museum and herbarium holdings. We support development of such data bases. [X-A7] 7. LTER sites. Ecologists have obtained important data from the several Long-Term Environmental Research (LTER) [IS THE NAME CORRECT?] sites situated in several biomes in the United States. In addition to data on long-term ecological and environmental changes, these sites hold the potential for studying long-term genetic changes in populations, including changes in characteristics that mediate organisms' responses to climate change. We suggest that the ecological research funded by NSF at these sites be complemented by carefully framed evolutionary studies. [WP COMMITTEE: THE FOLLOWING 3 ITEMS WERE RAISED BUT NOT SUFFICIENTLY DISCUSSED. SHOULD WE INCLUDE THEM? SEND RESPONSES TO STEERING COMMITTEE, I.E., MEAGHER, FUTUYMA, DONOGHUE, MAXSON, LANGLEY.] [X--8] 8. Research centers on evolutionary biology. We suggest that the community of evolutionary biologists discuss the advisability and feasibility of establishing one or more research centers for evolutionary biology. The major functions of such centers would be to (a) organize workshops of the kind described under [1] and [2] above; (b) provide work space for visiting scientists to support writing, data analysis, and interaction among subdisciplines; (c) manage data bases and electronic communication networks among evolutionary scientists. [COMMITTEE: IS THIS AT ALL ACCURATE? I'M UNCLEAR ON THIS ITEM. -DJF.] [X-A9] 9. Consider reorganizing foundational support for evolutionary research. The largest share of basic research in evolutionary biology is supported by the National Science Foundation. Research grants in the several subdisciplines of evolutionary biology are awarded from numerous divisions and panels within NSF. Although the current structure is suitable for funding research that lies squarely within many of the subdisciplines, interdisciplinary proposals often face difficulty, because some reviewers on several relevant panels are unfamiliar with the context into which the proposals fit. For example, research in the border between paleobiology and developmental evolutionary biology, between molecular genetics and evolutionary ecology, or between population genetics and systematics may face "double jeopardy" and difficulty in finding funding. We suggest that NSF consider the advisability of establishing a single unit, perhaps on "Biodiversity and Biotic Change," that could comprehensively address the spectrum of evolutionary research, including the interdisciplinary research that makes such conspicuous contributions to scientific progress. [X-A10] 10. National Committee on Evolutionary Biology. Although most evolutionary biologists recognize the value of interdisciplinary research, broad conceptual training of students, and a unified evolutionary biology, the exponential increase of research on many fronts in evolutionary biology has been accompanied, perhaps inevitably, by growth in the number of specialized societies and journals, by diverse annual meetings, and by a tendency toward increased specialization in students' research and perspectives. Efforts to counter these trends, such as joint meetings of the Society for the Study of Evolution, the Society of Systematic Biologists, and the Society for Molecular Biology and Evolution, have been enthusiastically received, pointing to the perceived need for mechanisms to unite the field. Moreover, it will be increasingly important for evolutionary biologists to speak with one voice in their interactions with the public (e.g., on misuses of evolutionary concepts), with educators, and with governmental and private agencies that support research (e.g., in developing applications of evolutionary biology to societal needs). We therefore suggest that the professional societies devoted to research and education in evolution explore the desirability and feasibility of a jointly sponsored steering or advisory committee on evolutionary biology. The structure and terms of its membership would be organized along principles similar to those that regulate the councils of professional societies. Its potential roles might include (a) establishing and maintaining an Internet site for disseminating information of broad interest; (b) responding to queries from funding agencies about trends and needs in research, and communicating generally held views to such agencies; (c) helping coordinate workshops and other mechanisms for advancing training and research; (d) communicating as needed with university administration and other educators on educational and training needs; (e) communicating important advances to the media; and (f) coordinating efforts in the public educational arena, on evolutionary aspects of topics such as racism, genetic engineering, and the conflict between creationism and evolutionary science. B. RESEARCH FUNDING [X-B1] The rate of progress and the accomplishments of a science are fundamentally dependent on the level of funding of research, and on policies and mechanisms that govern its disposition, such as research initiatives and allocations to large collaborative efforts compared to investigator-based programs. Like many scientific disciplines, evolutionary biology has felt the impact of the disparity between rising costs of research and increases in the budgets of funding agencies, which have lagged considerably. [SHOULD/CAN WE CITE SOME DATA? SOMEONE PLEASE PROVIDE A SUITABLE PASSAGE, A GRAPH WOULD HELP.] Large numbers of excellent proposals for unquestionably important research, submitted both by experienced researchers and innovative young scientists, are not funded because agency budgets have not grown to meet needs. The development of new directions in research, such as some advocated in Section IX of this document, can only exacerbate the inability of traditional sources of research funding to enable evolutionary biology to live up to its potential for progress on both basic and applied fronts. These considerations lead to the following recommendations for funding of evolutionary research. [X-B2] 1. Maintain funding for individual-based research programs. Considerable discussion has concerned the value of diverse research programs in individual laboratories, funded at a relatively modest scale, compared with large projects that require collaboration among numerous laboratories. In some fields of science, large-scale projects are effective and even necessary. On the whole, evolutionary biology is not such a field. It addresses numerous, highly diverse questions, rather than a few key questions, for no one discovery or sharply defined body of knowledge will remotely suffice to describe evolutionary history and its mechanisms, ranging from the molecular to the ecological level. Corresponding to the diversity of its subject matter, evolutionary biology has progressed due to the interplay and even conflict among ideas, principles, and data issuing from individual researchers in each of its several subdisciplines. One well-known model of evolutionary process, Wright's shifting balance theory, holds that adaptive progress in biological evolution is greatest when mutations and gene combinations arise and are screened by natural selection in each of many subpopulations, which exchange adaptive gene combinations at a sufficient level to bring about progress in the species as a whole. Whatever the validity of the theory may be for biological evolution, it is an apt metaphor for the conditions that seem to foster progress in evolutionary biology and some other sciences. [X-B3] We therefore affirm the preeminent value of individual-based research programs. This is not to deny that certain large, coordinated efforts play important roles. Examples might include development of data bases for phylogenetic and other data on biodiversity, data on human genetic diversity, and the like. [X-B4] 2. Model systems and diverse systems both make indispensable contributions. Some fields of biology progress largely by focusing primarily on a few model systems, such as E. coli bacteria, Caenorhabditis nematodes, and Arabidopsis plants. Likewise, certain areas of evolutionary biology, such as population genetics, have achieved great progress by utilizing the voluminous information and techniques available for model systems such as Drosophila. Many other subdisciplines of evolutionary biology can likewise profit from research on model systems; for instance, evolutionary developmental biology will be furthered by comparative studies of the groups (e.g., families) of organisms that include model organisms such as Drosophila, Caenorhabditis, and Arabidopsis. However, it is inherent in evolutionary biology, which aims to describe and understand the diversity of organisms and biological phenomena, and which achieves insights partly through comparisons of species, that it cannot restrict attention to a few model species. A balance must be maintained between studies of well- understood models and the rest of the biological world. [REPHRASE?] [X-B5] 3. The need is great for both increases in funding levels and for more diverse sources of funding of evolutionary research. [X-B6] A large proportion of basic research in evolutionary biology is supported by the National Science Foundation. Without denying the legitimate need of other disciplines for greater funding, commensurate with increasing costs and with enhanced prospects for progress in those fields, we emphatically support efforts by NSF to obtain increased budgets for research in the biological sciences that are progressing to unprecedented levels of understanding. Among these is evolutionary biology, in which progress in areas such as molecular evolution, the genetics, development, and evolution of phenotypic characters, phylogenetic analysis, and paleobiological analysis of the history of diversity has been exponential, and promises to continue. [X-B7] We have described the many ways in which a field of applied evolutionary biology is emerging. It will include both research that is immediately directed toward societal needs, and basic research that is clearly prerequisite to developing applications (e.g., methods for mapping quantitative characters, which will ultimately include desirable characteristics of wild species that may be used for transgenic domesticated organisms). Progress in these areas is closely related to the missions of diverse agencies, and will clearly contribute to their needs and goals. We therefore urge agencies that traditionally have supported little or no evolutionary research to expand their funding guidelines to include basic and applied research in those evolutionary disciplines that are related to the agency's mission. We also encourage researchers in the evolutionary disciplines to consider problems that directly or indirectly address societal needs, to demonstrate the value of their research for social applications, and to address their work to a variety of agencies. Examples of matches between agencies and evolutionary research areas relevant to the agencies' missions include: [X-B7a] --National Institutes of Health (NIH): Evolution and diversity of genome organization; molecular evolution; population genetic theory; QTL (quantitative trait loci) mapping; evolution of developmental mechanisms; evolutionary physiology; mechanisms of adaptation to environmental stresses; coevolution (of pathogens or parasites and hosts); numerical and analytical techniques for molecular data; genetic epidemiology; genetic diagnostics; evolution of drug resistance in microorganisms; human variation. [X-B7b] --National Institutes of Mental Health (NIMH): [SUGGEST ENTERIES?] [X-B7c] --National Institute for Human Genome Research: Population genetic theory and analysis; causes of genetic polymorphism; phylogeny and comparative analysis of genome structure; molecular evolution; QTL mapping; genotype/environment interactions; data analysis methods. [X-B7d] --U.S. Department of Justice: Genetic diagnostics; population genetics of molecular polymorphisms; analytical methods. [X-B7e] --U.S. Department of Agriculture (USDA): Genetic variation and QTL analysis of characters of plants; molecular evolution and developmental evolution in plants; plant breeding systems; evolutionary physiology of plants, domesticated animals, insects; natural pest resistance in wild plants; genetics, ecology, behavior, and systematics of plants, insects, nematodes, fungi, and other plant pathogens; parasite/host coevolution; genetics and evolutionary ecology of soil organisms; evolution of resistance to natural toxins and synthetic pesticides and herbicides; statistical and numerical data analysis. [X-B7f] --Environmental Protection Agency (EPA): Genetics, ecology, and evolution of bioremediation; microbial evolution; adaptation to global and local environmental change; genetics and adaptability of small and/or threatened populations; biodiversity (including systematics, biogeography, evolution of species interactions). [X-B7g] --U.S. Department of Interior, U.S. Fish and Wildlife Service: Bioremediation of damaged environments; evolutionary genetics and physiology of forest resources, fishery resources, aquatic organisms; adaptation to global and local environmental change; genetics and adaptability of small and/or threatened populations; evolution of life histories and breeding systems of harvested populations; biodiversity analysis (e.g., inventory, systematics, biogeography, remote habitat sensing, species interactions); theoretical, statistical, and numerical methods. [X-B7h] --National Biological Service (NBS): Biodiversity analysis (including aspects listed under previous heading). [SHOULD THEY BE REITERATED?] [DOES NBS STILL EXIST?] [X-B7i] --Department of Defense (DOD): Systematics, genetics, and evolutionary ecology of parasites, pathogens, and disease vectors; remote habitat sensing; systematics and evolutionary ecology of marine organisms; adaptation to global change. [ADD MORE?] [X-B7i ] --National Air and Space Administration (NASA); National Oceanographic and Atmospheric Administration (NOAA): [DO I HAVE THE NAMES RIGHT?] Biodiversity analysis of vegetation and marine systems (including systematics, biogeography, evolutionary ecology); impacts of species composition, species interactions, and genetic variation on ecosystem processes; remote sensing of habitats and organisms; adaptation to global and local environmental change; paleobiological studies of communities and environments in the past; statistical and analytical methods. [X-B7j] --Industry: The subjects of evolutionary research that should repay investment by industry are highly diverse, since industries concerned with pharmaceuticals, biotechnology, food production, cosmetics, pesticides, etc. have different, if overlapping, goals. The descriptions in Section IX of past and potential applications of evolutionary science to such goals as bioremediation, natural products development, and biotechnology make it clear that industries will variously find it useful to support research in such areas as: Comparative analysis of genes and genomes, QTL analysis of microorganisms; evolutionary genetics of transgenic organisms and their interactions with wild species; coevolution in microbial systems; adaptability and evolutionary ecology of soil organisms, weeds, and pest species; adaptive analysis of chemical properties of plants and other species; systematics and biodiversity of microorganisms, plants, and other species. It is important to note that conflicts can arise between the interests of industry, in which data, methods, and other information is privileged, and the interests of basic scientists, whose work and professional advancement often depend on dissemination of information. Funding of research by commercial concerns will require clear rules of engagement. [X-B7k] --Private foundations: Because of differences in goals among private foundations, specific suggestions for areas of potential support are inappropriate. However, private foundations can play a critical role in launching research directions that may not be readily funded by Federal agencies. Under this heading, proposals for research that is (a) truly innovative and therefore "high risk/high gain" in nature, (b) interdisciplinary, and likely to fall between the traditional areas funded by different agencies, or (c) important but out of fashion (perhaps because it entails amassing more data on traditional subjects) are especially likely to benefit from the flexibility that private foundations often can exercise. [X-B7l] --World Bank: [WAS MENTIONED AT CHICAGO WORKSHOP, BUT I HAVE NO IDEA WHAT TO ENTER] [X-B7m] --World Health Organization: [WAS NOT MENTIONED, BUT SHOULD/CAN SOMEONE SUGGEST ENTRIES?] ANY OTHERS?? C. EDUCATION [X-C1] Formal education both trains an informed citizenry that can make reasoned decisions and adapt to change, and trains the work force in each of the areas of specialized knowledge and methodology, such as science, on which society depends. Such "general" and "special" education are both essential for the progress of science and technology. Because of the critical role that education plays in the progress of basic evolutionary science and its applications to societal needs, we provide recommendations in the educational realm, including both formal schooling and provision of information to the working public. [FIND BETTER TERM THAN "WORKING PUBLIC" - REFERRING TO POST-SCHOOLING] [X-C2] 1. Training of secondary school teachers. Excellent education at the junior high and high school level is critical, both for college-bound students and others. Inadequacy of preparation of these students, especially in the sciences, is a widely recognized cause for national concern. The level of understanding of evolution and related subjects such as genetics is especially appalling. Due in part to its controversial nature, evolution is frequently given little or no coverage in high school biology curricula. Furthermore, many well-meaning, overworked teachers are unable to keep abreast of some of the most important progress in the field, and consequently provide inadequate, oversimplified coverage of the topic. [X-C3] We therefore recommend that agencies responsible for education increase efforts to retrain teachers, in evolutionary biology and related subjects, by supporting summer courses that will be rewarded by professional advancement. we urge professional biologists to contribute to such efforts. Such courses should emphasize the process of scientific inquiry (such as hypothesis testing and provisional conclusions), the progress in concepts and information that the subject has enjoyed, and the relevance of evolution to human life and societal needs. A variety of teaching materials, such as "Science as a Way of Knowing" (Moore _____), are available for such programs. [X-C4] 2. College and university curricula. Our comments concern course offerings for both biology majors and nonmajors. [X-C5] In many of most colleges and universities, a course on evolution is an elective, taken by a minority of biology majors, most of whom do not think it relevant to their medical or other careers. Often, the majority of majors will have little exposure to evolution beyond a few weeks (or less) in the introductory biology course. This does not prepare them to recognize or understand the relevance of evolutionary concepts and information to human health, agriculture, environmental science, or even to research in molecular biology or other biological disciplines. Biology departments in some leading universities, [CITE THEM???] having recognized that evolutionary concepts are as fundamental and integral to the biological sciences as genetics and molecular biology, have established a course on evolution as a requirement for all biology majors. Because of the unifying role that evolution plays in biology, its relevance to interpreting data in almost biological disciplines, its many demonstrated and potential applications to societal needs, and its position as one of the more important intellectual developments in the history of Western ideas, we strongly urge other colleges and universities to include evolution among the requirements for biology majors. [X-C6] Many biology departments offer nonmajors courses in critically important subjects such as genetics and ecology. For the reasons described above, evolution is equally important element in an educated person's understanding of biology. Well taught, such a course will intrigue and excite students, and provide them not only with technical understanding of issues that affect their lives, but also with a enlightened perspective on social and philosophical issues and a heightened understanding of the living history of ideas. We urge, in the strongest terms, that a nonmajors course in evolution be made available in every college and university. [X-C7] 3. Teaching tools. Contemporary secondary and college education makes increasing use of educational aids such as films, slide sets, and interactive computer programs. It will be necessary to supplement existing educational aids on the subject of evolution. We urge educational agencies and companies to develop such aids, and urge professional evolutionary biologists to contribute to their development. [X-C8] 4. Inclusion of evolutionary science in specialized advanced training. This document has made it clear that elements of evolutionary biology are profoundly relevant to fields such as medicine, public health, law, agronomy, forestry, natural products chemistry, and environmental science. However, postbaccalaureate training in most of these fields is virtually devoid of coverage of even the simplest, most relevant evolutionary concepts, such as the nature and importance of genetic variation. Moreover, we have noted that most students receive almost no education on evolution as undergraduates. We urge that professional schools and graduate programs in these fields incorporate relevant evolutionary material into their curricula, at the very least a few guest lectures by faculty in the field of evolutionary biology. [X-C9] 5. Graduate training in evolutionary biology and its applications. We have noted above (section X-A3) that training grants can contribute immeasurably to preparing graduate students for excellent, innovative research careers. To this, we add the importance of grants for doctoral research. In evolutionary biology, rather more than in some other biological disciplines, it is customary for Ph.D. students to do dissertation research that is thematically related to their advisor's research, but is not an integral part of the advisor's research and cannot be supported by the advisor's grant. This custom fosters independent thought, innovation, self-reliance, and learning beyond the advisor's sphere of knowledge, and it is suitable for a field that takes biological diversity as its subject. There exist funding programs for Ph.D. research in NSF and some other agencies [NAME THEM?], but in quantity incommensurate with the need and the prospective returns. We urge establishment of dissertation support by agencies that presently do not provide it. [X-C10] 6. College and university faculty positions. For both educational reasons, cited under numbers 2 and 4 above, and development of research excellence in modern biology, it is essential that biology departments of colleges and universities include faculty in several of the evolutionary subdisciplines. To address possible reservations, we note that the perception of evolutionary biology as an "old-fashioned" field is a misperception that could not be farther from the reality of a science that addresses cutting-edge [UGH] questions with state-of-the-art [UGH UGH] molecular, biochemical, computational, and mathematical techniques. The average grant for evolutionary research is larger than in the humanities but smaller than in physics or molecular biology; however, some grants, especially in molecular evolution, rival those in molecular or neurobiology. Faculty in evolutionary biology typically have a broad, interdisciplinary outlook that enhances communication with colleagues in other disciplines; they frequently are devoted, excellent teachers [NEED WE SAY THAT?]; and they very frequently attract some of the most outstanding graduate students in biology Ph.D. programs. Most importantly, evolutionary biology is an intellectually dynamic discipline that unifies biology and extends beyond it. [X-C11] Encompassing, as it does, a variety of subdisciplines from molecular evolution to systematics and paleobiology, no one faculty member can sufficiently represent the discipline. Indeed, many universities harbor departments or programs with names such as "Ecology and Evolutionary Biology", that include specialists in several or many evolutionary subdisciplines. The best such programs provide students with a balance, encompassing molecular evolution and organismal systematics, evolutionary physiology and plant evolution, evolutionary ecology and microbial evolution. Emerging disciplines such as developmental evolution and evolutionary neurobiology need to be complemented by older disciplines such as systematics and population genetics, which despite their age are addressing new questions with new methods and techniques. [X-C12] 7. Public outreach and education. Undoubtedly the greatest challenge to evolutionary biologists, and to all scientists, is to provide comprehensive, interesting information to citizens who have left school. Evolutionary biology faces the additional challenge of reaching and convincing a public that is largely skeptical or even hostile to the very concept of evolution. Although evolution is hardly controversial at all in many European and other countries, it is a politically and educationally volatile issue in the United States. (See Appendix.) Yet without its evolutionary foundation, biology is not a modern science, for however fully we describe biological phenomena, we cannot, as scientists, know their ultimate causes except with reference to evolutionary processes and history. Without evolution, many of the potential applications of biology to societal needs will remain undeveloped and even unexplored. No issue in public education about matters biological holds greater urgency or importance than communicating the nature, implications, and applications of evolution. [X-C13] It must be acknowledged that with some notable exceptions, most professional evolutionary biologists have devoted little effort to educating nonscientists. The burden of doing so has been carried by small organizations such as the National Center for Science Education (NCSE), by contributors to magazines such as The American Biology Teacher, and by a few evolutionary biologists (e.g., Stephen Jay Gould, Richard Dawkins) who have written for the lay person. [X-C14] In the strongest terms, we urge evolutionary scientists to become engaged with public education, and urge educational institutions to communicate the reality, vitality, and importance of evolution. Possible vehicles include: --Museum exhibits on modern evolutionary biology and the evidence for evolution; --Press releases on exciting advances in research; --Writing letters to newspapers and magazines, and urging coverage of the subject in science columns; --Giving public talks to local school and citizens' groups; --Monitoring textbooks and communicating reactions to publishers and school boards; --Addressing television and radio audiences when possible; --Supporting organizations that contribute to public education in biology. XI. CONCLUSIONS [XI-1] 1. Evolutionary biology plays critical roles in modern biology: [XI-1a] -It provides "ultimate" causal explanations, based on history and on processes of adaptation and genetic change, for the full sweep of biological phenomena, ranging from the molecular to the ecological, and thus expands and complement the "proximal" mechanistic explanations provided by other biological disciplines. [XI-1b] --It provides a theoretical framework and analytical methods for interpreting biological data, including data on humans, ranging from molecular genetic variation through physiology and behavior to the distribution of species and the structure of ecological communities. [XI-1c] --Using its comprehensive conceptual framework, mathematical genetic theory, phylogenetic analysis, comparisons of species, and other tools, it can discover phenomena of interest to mechanistic biologists (such as the sequence homogeneity of gene families within species and heterogeneity between species), and suggest possible mechanisms that can be tested by experiments. [XI-1d] --By describing species, variation within species, and phylogenetic relationships among species, it provides analyses of biological diversity that are the indispensable foundation for all biological studies that draw insight from studying different organisms. [XI-1e] --Employing the methods of paleobiology and systematics, it describes and analyzes history, which, in most sciences as in human affairs, provides insight into the present. [XI-1f] --It has demonstrated its ability to contribute to social needs, in areas ranging from medicine to the economic development of natural products and processes. [XI-1g] --It provides information and a conceptual framework for interpreting data on human genetic diversity, physiology, behavior, and culture, thus joining the many other disciplines that help us to understand ourselves. [XI-2] 2. In the broadest terms, the goals of evolutionary biology are to describe and interpret the history of life and to develop a full understanding of the causes and dynamics of evolutionary change, including those stemming from genetics, development, behavior, ecology, and changes in the environment and the earth. [XI-2a] Evolutionary biology has achieved enormous progress toward these goals, due to advances in concepts, theory, data analysis, computation, and molecular and other laboratory and field techniques. At present, evolutionary biology is probably more dynamic, and progressing more rapidly on diverse fronts, than at any other time in the last 50 years. By the same token, there exists great potential for continuing progress, for exploration of new realms, and for contributions to other biological sciences and to social needs. In basic science, we stand at the threshold [XI-2b] --of fully documenting biodiversity and describing the relationships among all organisms; [XI-2c] --of analyzing the history of life in greater depth than ever before; [XI-2d] --of discovering and explaining processes of evolution at the molecular level; [XI-2e] --of analyzing the molecular and genetic basis of characteristics that vary within and among species; [XI-2f] --of understanding how developmental mechanisms evolve and give rise to new phenotypic characteristics; [XI-2g] --of elucidating the mechanisms and the constraint on adaptations in physiology, endocrinology, and anatomy; [XI-2h] --of contributing to a deeper understanding of the adaptive meaning and the mechanisms of behavior; [XI-2i] --of developing a predictive theory of coevolution between species, such as pathogens, parasites, and their hosts, and of the impact of coevolution on populations and ecological communities. [XI-2j] In the applied realm, , evolutionary biologists are embracing their social responsibility, and are becoming increasingly aware of the many ways in which their discipline can help [XI-2k] --to understand and combat genetic and infectious disease; [XI-2l] --to improve crops and mitigate damage from pathogens, insects, and weeds; [XI-2m] --to provide tools for analyzing human genetic diversity as it applies to health, law, and the understanding of human behavior; [XI-2n] --to aid responsible economic use and development of biological resources; [XI-2o] --to remedy damage to the environment; [XI-2p] --to predict consequences of global and regional environmental change; [XI-2q] --to conserve biodiversity, potentially faced with the most massive extinction in the last 65 million years. [XI-3] 3. In view of the role of evolutionary principles and data in the biological sciences, of the applications of evolutionary science to social needs, of the significance of the evolutionary perspective in understanding the human organism, and of contemporary progress in evolutionary research, we urge that structural mechanisms be established and supported to foster the continued progress of basic and applied evolutionary science. Such mechanisms include [XI-3a] --regular interdisciplinary workshops, to further the integration of the subdisciplines of evolutionary biology with each other and with other scientific disciplines; [XI-3b] --intensive training workshops on new techniques; [XI-3c] --training grants for graduate student education and research; [XI-3d] --enhanced postdoctoral and midcareer opportunities; [XI-3e] --intensified research in certain insufficiently studies areas; [XI-3f] --coordination of communication among the evolutionary disciplines and with institutions that support or stand to benefit from evolutionary research; [XI-3g] --and, possibly, reorganization of structural mechanisms for funding research in evolutionary biology. [XI-4] 4. In view of the importance of evolutionary research as described earlier, and especially of its diverse applications to practical social needs, we urge [XI-4a] --that evolutionary biologists communicate to Federal agencies, and to other institutions that support basic or applied research, the relevance of evolutionary biology to these institutions' missions; [XI-4b] --that such agencies and institutions support evolutionary research consonant with their missions. Elements of basic and applied evolutionary research are highly relevant to the mission not only of the NSF, but also NIH, NIMH, USDA, EPA, DOD, NASA, NOAA, the National Institute for Human Genome Research, the Department of Justice, the Department of Interior, the U.S. Fish and Wildlife Service, the National Biological Service, and a variety of industries and private foundations. [XI-5] 5. In view of the relevance of evolution to many human endeavors and of the importance of scientific literacy in an increasingly scientific and technological world, we urge that major efforts be made by biologists, educators at all levels, and agencies concerned with education and public discourse to strengthen curricula in both secondary schools and colleges and universities with respect to modern evolutionary biology and its implications for society, and to improve public understanding of this fundamentally important science. We call for [XI-5a] --support of midcareer training of school teachers; [XI-5b] --greater emphasis on evolution in the curricula expected of biology majors and available to nonmajors in colleges and universities; [XI-5c] --integration of relevant evolutionary concepts into the postbacculaureate training of all biologists and of professionals in medicine, law, agronomy, and certain other professions; [XI-5d] --enhanced support of graduate education and research in evolutionary biology and its applications; [XI-5e] --more faculty positions in evolutionary biology, especially in understudied subdisciplines, in colleges and universities; [XI-5f] --active contributions from biologists, science writers, media representatives, museum administrators, and public educators toward informing the public about the nature, progress, and implications of evolutionary science. [XI-5g] [Someone] has said that as physics has shaped the science and technology of the present century, so biology will shape the twenty-first century. [COLLEAGUES: HELP! WHAT'S THE PHRASE AND BY WHOM?] Provided the resources and public support, evolutionary biology will play an indispensable role. [APPENDIX] EVOLUTION: FACT, THEORY, CONTROVERSY [1] We have just referred to the theory of evolutionary processes. We use "theory" as it is used throughout science, to mean not a mere speculation or an unsupported hypothesis, but rather, as The Oxford English Dictionary puts it, a theory is "a scheme or system of ideas and statements held as an explanation or account of a group of facts or phenomena; a hypothesis that has been confirmed or established by observation or experiment, and is propounded or accepted as accounting for the known facts; a statement of the general laws, principles, or causes of something known or observed" (our italics). The complex body of principles that explain evolutionary change is a theory in the same sense as "quantum theory" in physics or "atomic theory" in chemistry: it has been developed out of evidence, tested and refined, and it accounts for literally thousands of observations made throughout the entirety of biological science and paleontology. Like all scientific theories, the theory of evolutionary process is a current best explanation. Although it has withstood innumerable tests and attempts to disprove it, it still can be refined, modified in the light of new knowledge, extended to account for newly discovered phenomena. The theory of genetics has had such a history, from Mendel's simple, early principles to the complex body of molecular principles that constitute today's theory of inheritance, and which is constantly being refined and modified, even though its core principles have remained valid for a century. So it is with the theory of evolution. [2] Is evolution also a fact? All but the most trivial facts begin life as untested hypotheses -- such as the hypothesis that the earth revolves about the sun. They acquire "facthood" as more and more evidence accrues in their favor, and as they withstand attempts to refute them. The evidence and attempted refutations may take many forms besides simple observation; indeed, the most powerful evidence is not mere observation, but conformity to predictions that the hypothesis makes about what we would see if the hypothesis were true versus false. We do not observe the earth make a circuit about the sun; we accept this hypothesis because of the numerous, verified astronomical observations that conform to the predictions of this hypothesis. So Copernicus's hypothesis is now a fact -- a statement supported by so much evidence that we use it as if it were true -- although it is remotely conceivable that it is not. (As philosophers have suggested, it is also conceivable that neither we nor the rest of the universe exists at all, but that everything is a dream in the mind of a deity. But we act as if the substantive reality of the world were a fact.) [3] Biologists almost universally regard the historical reality of evolution as a fact. That is, they accept as a fact that all organisms, living and extinct, have descended, with innumerable changes, from one or at most a few original forms of life, several billions of years ago. For Darwin in 1859, this was a hypothesis, for which he provided abundant evidence from comparative anatomy, embryology, behavior, geology, and the geographic distribution of organisms. Since Darwin, every one of the many thousands of observations in each of these areas has supported Darwin's hypothesis. To this evidence has been added mountains of evidence that Darwin could hardly have hoped for or even dreamed of, especially from paleontology and molecular biology. A century's accumulation of such evidence, with more accruing each day, establishes descent, with modification, from common ancestors as a fact of life. How we explain this fact -- what the principles and causes of it may be -- is the theory of evolutionary process, which as we have noted is subject to debate, modification, and extension. [4] To claim evolution as a fact is to confront controversy -- for probably no claim in all of science evokes as much emotional opposition as biological evolution. Nonetheless, no scientific hypothesis other than common descent with modification can account for the unity, diversity, and properties of living organisms. No other hypothesis is supported by any evidence whatever, and no other hypothesis spawns such richness of scientific study and has as many implications for the biological sciences and their applications to social needs. (REWRITE THIS??) [INTEGRATE THE FOLLOWING WITH THE PRECEDING] [5] Evolution and Spiritual Belief: A Necessary Conflict? [5a] Since its inception, evolution has been more consistently controversial - in the public eye, not among scientists - than any other issue raised by science, because it is widely perceived to be incompatible with religious beliefs, especially about human nature and origins. To this day, opposition continues, at a higher pitch in the United States than in most European countries, including those with state-established religion. The so-called creationist opposition to evolution is so vocal in the United States that it has threatened Federal funding of explicitly designated evolutionary research, despite its basic scientific value and numerous applications. Equally importantly, the public school systems are driven to minimize education in evolutionary science, contributing to widespread scientific illiteracy. (A 1988 study compared teenager's command of science ranked Americans in the lowest 25 percent, behind students in countries such as Japan, England, and Hungary.) Almost half of Americans believe that man was created in pretty much his present form about 10,000 years ago, even though the reality of evolution - including human evolution - has not been seriously controversial among scientists for almost a century. [5b] Evolution is indeed incompatible with a literal interpretation, as scientific fact, of the stories of the creation and the deluge in the Book of Genesis - just as physical science is incompatible with the Bible's story that the sun stood still at Joshua's [???] command (Bible citation). However, most western religions, recognizing that pastoral peoples millennia ago did not know about (and even if told, could not possibly have understood) molecules, genes, and the rest of modern science, interpret the Biblical account of creation as parable, conveying spiritual truth and values, but not to be understood today as literal fact. Priests, ministers, and rabbis have affirmed the validity of science - some indeed teach about evolution and even do evolutionary research - while also affirming the spiritual validity of the Bible's teachings. Many people - perhaps a majority of Americans who have given the matter any thought - maintain belief in a deity while allowing the deity to create via natural processes, including evolution. Evolutionary biologists themselves include a small minority of militant atheists, a majority who hold deep ethical values while remaining agnostic or vague about their belief in a supernatural being, and a considerable number who are devout participants in various religions. Whether or not belief in God and in evolution are compatible is a matter if individual decision, and cannot be decided by science, which by its nature is limited to determining natural causes, cannot pronounce on supernatural matters, and cannot provide answers to ultimate philosophical or ethical questions. [5c] This last point needs emphasis. Anti-evolutionists have charged that evolution robs society of any foundation for morality and ethics, that it teaches a materialistic world view which would justify the principle that might makes right. But evolutionary science has never taught any such thing, and if properly exercised cannot teach any such thing, for science in itself has no moral or ethical content, for good or ill. Whether the science be physics or evolutionary biology, it teaches us what the world is like and how it works, not what it should be like. Indeed, physics, chemistry, physiology, and neurobiology should be as threatening to those who fear evolution as evolution itself, for those studies, exactly like evolutionary biology, admit no supernatural causes for the actions of atoms, the sun's energy, the health or ills of the human body, or the powers of the human brain. These sciences are materialistic to the core, and we rely on their material theories when we build airplanes, synthesize new plastics, listen to weather reports, or consult our doctors. Most Americans prefer a doctor who relies on materialistic biology over one who would cure us by prayer. Nor would we seek moral guidance from medical doctors or chemists. So with evolutionary science: no more nor less materialist than any other science, it offers no moral guidance, only dispassionate analysis of how biological systems function and came to be. What use we make of such information is for society to decide. (BOX 1) [B-1] Frog alkaloids Knowledge of evolutionary (phylogenetic) relationships has helped guide research scientists to the discovery of natural compounds useful in biomedical research. For example, poison frogs are a closely related group of New World tropical amphibians found in Central and South America. Their poisons are based in a class of chemical compounds called alkaloids, which the frogs may obtain from small insects and other invertebrates in their diet and later release in defensive skin secretions. The alkaloids of three species of these frogs are used for poisoning the blowgun darts of native forest hunters in western Colombia. Batrachotoxin, isolated from these poison-dart frogs, has proven useful in studying the effects of local anesthetics, anticonvulsants, and other drugs. Alkaloids of the pumiliotoxin class from a Central American poison frog have been shown to have cardiotonic (heart stimulating) activity. Epibatidine, an alkaloid isolated from the skin of a South American poison frog, is 200 times more powerful than morphine as an analgesic (painkiller), and commercial synthetic material is now being widely studied because of its potent nicotine-like activity. These are a few of the medically relevant compounds first discovered in tropical poison frogs. By working closely with evolutionary biologists and systematists who help locate, identify, and describe new species of poison frogs, research scientists continue to identify new compounds useful in biomedical research. References Badio, B., H. M. Garraffo, T. F. Spande, and J. W. Daly. 1994. Epibatidine: discovery and definition as a potent analgesic and nicotinic agonist. Med. Chem. Res. 4: 440-448. Others can be supplied by Myers and Daly (via Hanken) on request. Illustrations Cladogram depicting phylogenetic relationships among the three species discussed above: Epipedobates tricolor, Phyllobates terribilis, and Dendrobates pumilio. Should we leave in the names of the alkaloids, as in the draft figure provided by CWM (see his note)? Photographs of Epipedobates tricolor, Phyllobates terribilis, and Dendrobates pumilio. (Provided by C. W. Myers.) Should we put the photo of each frog at the top of their respective branch of the cladogram? Authors Charles W. Myers, Department of Herpetology and Ichthyology, American Museum of Natural History, New York, NY 10024 John W. Daly, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 Compiled by J. Hanken (BOX 2) [B-2] Human Immunodeficiency Virus Many viruses, and most notably the human immunodeficiency virus (HIV), exhibit enormous genetic diversity, a diversity which can often arise within thetime-frame of human observation and frequently hinders our attempts at control and eradication. Evolutionary biology has played an important role in describing the extent of this variation, in determining the factors which have been responsible for its origin and maintenance, and examining how it may influence the clinical outcomes of an infection. It is possible to illustrate the importance of the evolutionary analysis in this context, and particularly with HIV for which most data is available, at three different levels; on a global scale, within infected populations and in individual patients. Globally, evolutionary trees have shown that the two immunodeficiency viruses, HIV-1 and HIV-2, arose separately from simian ancestors and that within each virus there is considerable genetic variation which can be organised into distinct "subtypes". These subtypes differ in their geographical distribution (although most found in Africa) and possibly in important biological properties. For example, subtype E from South-East Asia appears to be more easily sexually transmittable than other subtypes and is associated with the recent dramatic spread of the virus through this part of the world. The correct identification of subtype through phylogenetic analysis will therefore be a critical element in the design of future vaccines. Within infected populations, evolutionary analyses have led to important epidemiological hypotheses about where HIV strains have originated, and particularly those associated with "low risk" behavioural groups, and whether different risk groups possess characteristic strains. This information will form an important part of behavioural intervention programs as it will be possible to accurately identify those groups which are most involved with the spread of HIV. An evolutionary approach has also been central to answering questions about whether HIV can be passed to the patients of health care workers, for example during surgery (Figure). Finally an evolutionary approach has produced invaluable information about the dissemination of HIV within a single infected patient. In particular it has been possible to determine how and where genetic diversity arises during the course of an infection, whether particular variants of HIV are associated with the onset of AIDS or with the infection of specific organs such as the brain, how the dynamics of viral replication are affected by drug therapy and how the evolutionary interaction between virus and immune system may determine how HIV eventually causes AIDS. In this respect an evolutionary perspective is central to understanding the basic biology of HIV. 3