|
 |
|
|
|
THIRTY-TWO KEY CONCEPTS OF GENETICS |
|
|
|
|
|
This is a very condensed summary of the key concepts to be covered in genetics, AGR
3303. I have written these concepts as simple declarative statements, grouped in six
major categories. This summary will be difficult to read until after you have read
the appropriate chapters in Klug and Cummings. Therefore, you should use this as a
review of what you already know. |
|
|
|
|
|
GENETICS IS THE STUDY OF HEREDITY, THE TRANSMISSION OF TRAITS. |
|
|
|
|
|
| 1. |
The use of heredity to breed plants and animals is
ancient. |
|
|
|
While practical genetics was useful, it was not known as a
science until 1900. Several erroneous ancient ideas impeded progress, including the
inheritance of acquired characteristics based on the doctrine of use and disuse, the idea
of spontaneous generation, and the belief in the fixity of species. Significant
genetic advances occurred after an understanding that organisms are made of cells, that
life can be made from inanimate chemical substances (atoms and molecules), and that
heredity can also be viewed as the transmission of particles called genes.
Systematic observation and a willingness to suspend earlier viewpoints made this
possible. Genetics is a great intellectual achievement. |
|
|
|
|
|
|
| 2. |
There are four main genetic capabilities. |
|
|
|
They are replication (copying), information storage, gene expression, and
mutation. |
|
|
|
|
|
|
| 3. |
Genetics is more than the study of transmission from parents to
offspring. |
|
|
|
Genetics explains the development of cells and organs, the interaction of
the organism with its environment (e.g., differentiation, the regulatory cascade, and
antibody response), the interaction among organisms (e.g., parasitism and social
behavior), diversity among and within species, and evolution of new species.
Genetics unifies all aspects of biology, and cybergenetics (a new word I just made up) has
been used to solve mathematical problems. One view is that biology is a branch of
genetics. |
|
|
|
|
|
|
THE BEHAVIOR OF CHROMOSOMES IN THE CELL CYCLE PROVIDES CLUES TO INHERITANCE. |
|
|
|
|
|
| 4. |
The same chromosomes (and genes) are present in virtually all the
cells of the organism. |
|
|
|
Eukaryotes (organisms with nuclei) are usually multicellular. Typical,
diploid eukaryotes have two nonidentical copies of each chromosome; these are located in
the nucleus. Their gametes are haploid, containing only one copy of each chromosome.
Members of a species tend to have the same chromosome number. You are diploid, and
like other humans, would normally have 46 chromosomes; your gametes (sperm or eggs) have
23 chromosomes. When gametes fertilize, the new zygote has two copies of each
chromosome, thus 46. This maintains continuity across generations, an important
biological characteristic. |
|
|
|
|
|
|
| 5. |
Mitosis and meiosis are different forms of cell division (identical
and nonidentical). |
|
|
|
Nondividing chromatin (chromosome material) is relaxed and genetically
active; dividing chromatin is condensed and genetically inactive.
Mitosis is a process
of identical division, and occurs in most of the cells of the body; therefore, it is
sometimes called somatic division. In mitosis, two identical chromatids of each chromosome
separate, cleaving the centromere, and produce two identical daughter cells. There
is no reduction in number of chromosomes; genetic information is the same; this is
cloning.
Meiosis reduces by half the chromosome number in the daughter cells (reducing the
genetic information), is nonidentical division, and occurs only in the germ cells which
produce gametes. Meiosis consists of two divisions producing four nonidentical
daughter cells. The first division is reductional, that is, the number of
chromosomes in each daughter cell is one-half the number in the original. In the
first division, similar chromosomes form pairs (each pair is composed of four chromatids
containing two centromeres in a tetrad) and then divide reductionally (paired chromosomes
and centromeres separate or disjoin from one another), resulting in half the number of
chromosomes and centromeres in each of the two daughter cells. Different pairs
separate independently, which is consistent with the independent assortment of genes
observed by Mendel. When there is crossing over (reciprocal exchange of chromatid
arms), daughter cells have a mixture of sister and nonsister chromosome material. The
second division of meiosis is primarily similar to mitosis.
Stages of cell division (mitosis and both divisions of meiosis) are prophase (chromatin
condensation and, if meiosis, pairing), metaphase (movement to a central plane), anaphase
(dividing and moving apart to two poles), and telophase (chromosomes at opposite poles,
but the cell has not yet divided). During interphase, prior to cell division, DNA
synthesis occurs.
|
|
|
|
|
|
|
INHERITANCE CAN BE EXPLAINED BY MENDEL'S "UNIT FACTORS," THE GENES. |
|
|
|
|
|
| 6. |
Biological traits are transmitted as units from parent to offspring;
this is inheritance. |
|
|
|
Inheritance is explained by unit factors called genes. Just as a
trait (e.g., eye color) can take different forms (blue eyes versus brown), a gene can take
two or more different forms, called alleles; the form of the gene determines the trait.
So the same gene can make blue eyes or brown eyes, due to its different forms.
New alleles arise rarely as mutations, which involve spontaneous or induced changes
from previous alleles. All the many traits of an organism are determined by its
genes, collectively, the genotype, interacting with environmental factors, to result in
the organism we see, the phenotype. The distinction between nature and nurture helps
explain main things. |
|
|
|
|
|
|
| 7. |
Female and male parents contribute equally to the traits of the
offspring, which thus has a pair of units, two copies, of each gene. |
|
|
|
Because the parents have two copies, they may furnish only half, or one
unit, of each gene, in their reproductive cells, the gametes. Typically, two
gametes, from male and female parents, will unite to form a zygote, the first cell of a
new offspring organism. The genes of the two parents are never blended; rather, the
traits of their offspring fall into discrete categories similar to those of the parents
(though they may appear to be blended, see #16), as though the units of inheritance had
not been altered through the passage across generations, but were merely
transferred. Heterozygotes are genotypes whose offspring segregate, or vary for
particular traits; they have contrasting alleles for a particular gene. Homozygotes
do not display segregation; they have two identical copies of the same allele for a
particular gene. |
|
|
|
|
|
|
| 8. |
Each trait is determined based on rules governing allelic
relationships for a specific gene. |
|
|
|
An allele which overrules another allele of the same gene is
"dominant"; its subjugated partner is "recessive". (From what you know
of the multiple allelic system that controls human ABO blood types, can you match all
possible genotypes with their respective phenotype?) An intermediate condition is
incomplete or partial dominance, that is, contrasting alleles in the same organism (a
heterozygous genotype) produce an intermediate level of a trait, compared to the two
possible homozygotes. Codominance is another relationship, when the heterozygote has
a trait containing qualitative features of both parents. Sometimes two traits can be
affected by the same gene; this is pleiotropy. (There are also rules by which two or
more genes can determine a single trait; the concepts epistasis and polygenic inheritance
will be introduced later.) Pedigrees show that traits are passed from parents to
offspring by these rules. Can you determine the genotype of the parent by knowing
the genotype of its progeny? |
|
|
|
|
|
|
| 9. |
The distribution of genotypes in a progeny follows rules of chance. |
|
|
|
Crosses among the heterozygotes produce a 1:2:1 genotypic ratio
(homozygous dominant : heterozygous : homozygous recessive) in the progeny. This would
show a 3:1 phenotypic ratio (dominant trait : recessive trait). What kind of
heterozygotes are these? [For two genes, i.e., a dihybrid cross, their progeny would be in
the genotypic ratio 1:2:1:2:4:2:1:2:1 (9:3:3:1 phenotypic ratio)]. This assumes
independent assortment (but see linkage, below). These results could be determined
from the product law, that is, the probability of independent events occurring
simultaneously is the product of their individual probabilities. Can you solve
Mendelian genetics problems; if you know the genotype of the parents, what is the
frequency of genotypes in the progeny? |
|
|
|
|
|
|
| 10. |
Observed frequencies can differ from expected frequencies. |
|
|
|
When larger and larger numbers of offspring are evaluated, the closer and
closer do their observed frequencies approach the pattern expected from a random
assortment of units. The chi-square test helps referee close calls. For
example, let the null hypothesis be, "the true ratio is 3:1". Even if this
expectation were true, observed results will sometimes differ from the expectation. If 3:1
is true, then the expectation in a progeny of 100 will be 75:25. Even if 3:1 is true,
sometimes (10% of the time) you will observe results as far off as 82:18 in an actual
segregating progeny. Rarely (0.1% of the time) will you observe 89:11, even if 3:1
is true. The farther the observed results are different from the expectation, the
less likely (the smaller probability) that results would be by chance. Typically,
when the probability (P) is only 0.05 (5%) then we reject the null hypothesis, and look
for some other explanation. The chi-square value is just an intermediate number used to
look up the probability in a table. |
|
|
|
|
|
|
| 11. |
Genes on the X-chromosome show criss-cross inheritance and other
unusual patterns. |
|
|
|
In humans the male is the heterogametic sex, having both an X and a Y
sex-determining chromosome; the females have two X chromosomes. (The remaining 44
chromosomes are autosomes). Genes located on a sex chromosome are called sex-linked;
because the Y chromosome contains very little information (other than a sex determining
factor), sex-linkage essentially always involves the X chromosome. Important
recessive, sex-linked traits in humans include hemophilia, color blindness, and muscular
dystrophy. Because males have only one copy of sex-linked genes (hemizygous), the
recessive traits are expressed in the male if he receives a copy of the gene from his
mother. Females rarely express sex-linked traits, because they rarely receive a copy
of the recessive allele from both parents. Consequently, one can refer to
"female carriers" of a sex-linked trait. Another sex-linked trait, coat
color in cats, shows an unusual pattern. Calico cats are females whose X chromosomes
differ allelically for the coat color gene. According to the Lyon hypothesis, one or
the other of the female's X chromosomes is randomly inactivated to form a Barr body.
This occurs independently for different cells during the early divisions of embryo
development, and all daughter cells retain the same inactivated X chromosome; the allele
on the active X chromosome conveys a coat color to the patch which developed from one of
the early cells. |
|
|
|
|
|
|
| 12. |
Genes close to one another on the same chromosome do not assort
independently, but are linked. |
|
|
|
This situation is noticed in the cross of an organism homozygous dominant
for two genes crossed with another which is homozygous recessive for the same two genes.
If the genes are on the same chromosome, in the F1 zygote they will be in
coupling, that is, the dominant alleles for the two different genes will be on the same
chromosome, and the recessive alleles for the two genes will be on the other chromosome.
If
the F1 is backcrossed to the double homozygous recessive parent, a tester, then
there will be more noncrossover progeny than crossover progeny. (Noncrossover
progeny include both the double heterozygote and double homozygous recessive, while the
crossover progeny would be heterozygotic for only one gene).
Because crossing over involves only two of the four chromatids, the maximum possible
crossing over is 50%. Genes are mapped on chromosomes according to the percent
crossing over; physical distance agrees closely to map distance and the number of linkage
groups agrees is equal to the haploid chromosome number. With three genes, to find
their order, first identify the two noncrossover and the two double crossover gametes (or
testcross progeny) based on their being the most and least frequent, respectively, of
eight possible classes. Then, decide which of three possible gene sequences would
have resulted in such a double crossover. Do this either by trial and error, or by
realizing that among double-crossovers the two genes which stay together in the same
allelic relationship as the noncrossover gametes are flanking the third gene locus.
Once you know the gene order, figure the map distance based on the percent of single
crossovers between adjacent genes. Make sure to add the double crossover frequency
to each. Finally, considering the order, add crossover distances between adjacent
intervals to find the distance between the genes farthest apart.
|
|
|
|
|
|
|
| 13. |
Variations in chromosome number and structure have major consequences. |
|
|
|
Plants are more tolerant than animals. Euploidy involves multiple
copies of complete sets of chromosomes: haploid (e.g., gametes), diploid (typical
zygotes), and polyploid (more than two sets (e.g., triploid, tetraploid, etc.).
Triploids (e.g., seedless watermelons) are often sterile. Other examples of
autopolyploids exist among plants. Allopolyploidy (polyploidy through the
acquisition of two sets of chromosomes from two or more species) was important in the
origin of bread wheat, cotton, and many other crop plants. Such plants are fertile,
because the chromosomes have homologs with which to pair. Aneuploidy involves chromosome
numbers different from complete sets, e.g. trisomic (one extra chromosome, Down syndrome
in humans), and monosomy (one less). Variations in structure do not change the
amount of genetic information, but can create position effects, and can affect fertility
and future generations. Variations include deletion, duplication, inversion, and
translocation, which greatly affect chromosome pairing and disjunction. |
|
|
|
|
|
|
| 14. |
The distribution of genotypes in a population follows rules of chance. |
|
|
|
If you know the genotypic frequencies in a population, an interbreeding
group, you can predict the genotypic frequencies in the next generation. First, calculate
allelic frequencies from the genotypic frequencies (e.g., p = frequency of allele A and q
= 1-p = frequency of allele a). Then, expand these frequencies by squaring (p+q)2
= p2 + 2pq + q2, another example of the product law. |
|
|
|
|
|
|
| 15. |
Allelic frequencies can change because of several forces. |
|
|
|
The Hardy-Weinberg Law holds that allelic frequencies and genotypic
frequencies remain in equilibrium (do not change) in the absence of mutation, nonrandom
mating, or selection (differential reproduction). There must also be an infinitely
large population, or else genetic drift (random loss of alleles) will occur.
Violations of Hardy-Weinberg assumptions cause changes in allelic frequencies in a
population, which can lead to long-term genetic changes (evolution). While mutations
are assumed to occur rarely, and have little short-term effect, in the long-term they can
be important, providing new alleles on which natural selection can operate. Can you
tell how allelic frequencies will change if one genotype (e.g., the homozygous recessive)
does not reproduce? |
|
|
|
|
|
|
| 16. |
Continuous variation results from many genes with small effects. |
|
|
|
Although the classical Mendelian units of inheritance are easy to
comprehend for categorical traits, e.g., eye color, they are probably exceptional among
the many traits which determine the appearance and success of the genotype. To
explain traits showing a continuous range of variation (no discrete categories) the
concept of quantitative (=polygenic) inheritance has been described as the effect of many
genes controlling the same trait, typically in an additive fashion. Polygenic
inheritance (due to the additive effect of many genes; see below) produces each of the two
most extreme classes of genotypes with a frequency of (1/4)n, where n=number of
genes that control the trait, also by the product law. Can you tell how many genes
control a trait by looking at the distribution of phenotypes? Many genes with small
effects can tend to smooth out the categories in a Mendelian distribution, such that steps
are not discernible. (Qualitative inheritance refers to categorical Mendelian
traits; these concepts are only relative.) In the viewpoint of quantitative inheritance,
environmental factors are blended with genetic factors to produce the phenotype. Because
frequencies do not exist for quantitative inheritance, it must be studied through
statistics (the evaluation of uncertainty in inductive inferences) applied to bell-shaped
("normal") distributions. Statistics are determined from samples; they
estimate parameters of the population. One statistic, the variance, is a good
measure of dispersion; it is additive and does not change with the sample size. (A
statistic is only as good as the sample.) Phenotypic variance VP can be partitioned
into its variance components, genotypic (VG), environmental (VE), and genotypic X
environmental interaction VGxE. Heritability, the genetic resemblance between parent and
offspring, is the ratio VG/VP. Can you provide an example of genotype X environment
interaction? |
|
|
|
|
|
|
INHERITANCE IS TRANSMITTED THROUGH DNA, A POLYMERIC CHEMICAL WHICH IS ITS OWN
TEMPLATE. |
|
|
|
|
|
| 17. |
The composition and structure of DNA help explain its function. |
|
|
|
(By the way, what are the four characteristics of the genetic material?)
(Also, what other polymeric biomolecules are there?) DNA was known since 1868, but DNA's
role in heredity was established between 1944 and 1953. DNA is made of building blocks
called nucleotides, each consisting of three elements: a 5-carbon sugar (deoxyribose), a
phosphate group, and a nitrogenous base, all attached by covalent bonds. The ability of
DNA to direct life derives from the four kinds of nitrogenous bases: thymine=T and
cytosine=C, pyrimidines; and guanine=G and adenine=A, purines. Two-stranded DNA is a
right-handed double helix of complementary (A=T and C=G), antiparallel strands
which are held by hydrogen bonds. This "Watson-Crick model" for the DNA
structure was based on X-ray diffraction and base composition. What are the ratios of
nitrogenous bases and how must these relationships follow from structural complementarity?
The double-stranded DNA can take several forms. Can you illustrate the structure of DNA
showing the paired bases as rungs of the helical ladder? Which positions of the
deoxyribose are joined to phosphate groups? Some functional aspects of DNA are immediately
obvious from the structure, including the potential for copying and the storage of
information. |
|
|
|
|
|
|
| 18. |
There are several evidences for DNA as the genetic material. |
|
|
|
Avery et al., 1944, showed a "transforming principle" of
bacteria was inactivated by DNase. Another experiment showed that the infectious agent
from a phage (a bacterium-attacking virus) contains radiolabelled P, not S.
Circumstantially, the action spectrum of DNA is similar to its UV absorption. One of the
strongest proofs is that human insulin DNA can be used by bacteria to produce insulin.
Sometimes RNA is the genetic material; it differs from DNA in base composition (uracil
instead of thymine), substitution of the 5-carbon sugar ribose for deoxyribose, and the
fact that RNA is usually single-stranded, while DNA is usually double-stranded. (RNA
occurs as mRNA and tRNA, described in #24, and rRNA = ribosomal RNA, all of which are
important in the genetic machinery). Why were bacteria and viruses useful in early studies
of the genetic material? |
|
|
|
|
|
|
| 19. |
Replication (copying) is one of the main functions/requirements of a
genetic material. |
|
|
|
Copying of DNA (replication) is semiconservative, (based on labeling
experiments), bidirectional (always 5' to 3', referring to the carbon atoms in the sugar),
and high fidelity (based on nearest-neighbor analysis). Replication is performed by an
enzyme called "polymerase," which can only operate in the presence of a
"primer," a DNA sequence (polynucleotide) needed to start the process. Compared
with prokaryotes, replication in eukaryotes is more complex and slower in eukaryotes, and
involves a greater number of factors, replication at multiple origins, and split genes. |
|
|
|
|
|
|
| 20. |
Genetic information is a coded DNA message. |
|
|
|
(The central dogma of molecular biology is DNA > mRNA >
polypeptide, see #24, below.) Realizing that most enzymes are made up of 20 amino acids,
how can we explain the diversity of enzymes based on an information system with only four
possible nucleotides? The genetic code is a triplet RNA code; it is + universal,
linear, degenerate (=redundant), unambiguous, nonoverlapping, and comma free, but with
some punctuation signals (e.g., nonsense codons, below). A set of three RNA bases, coding
for a single amino acid, is called a "codon." There is a collinear relationship
between the ordered sequence of nucleotide triplets and amino acids. There are four
possible nitrogenous bases at each of the three positions in the codon triplet, thus there
are 43 = 64 possible codons. These are more than enough to specify about 20
possible amino acids, including redundant codons, plus three nonsense (terminator) codons,
and an initator codon (AUG). Experimental decoding was based on a cell-free synthesizing
system (e.g., homopolymers and heteropolymers); more direct evidence was based on triplet
binding and sequencing (387 nucleotide pairs > 129 amino acids). |
|
|
|
|
|
|
| 21. |
Mutations in structural genes help explain gene action. |
|
|
|
Mutational changes in structural genes (e.g., those that produce
proteins) are changes in the nucleotide sequence. The different mutational forms of the
gene are alternative forms of Mendel's unit factors, the alleles. Sometimes mutations lead
to no effect on amino acid sequence (due to degeneracy in the code); sometimes mutations
lead to changed amino acid sequence, e.g., sickle-cell-anemia globin polypeptide (which
forms hemoglobin); other kinds of mutations affect other aspects of gene expression. |
|
|
|
|
|
|
| 22. |
DNA can be manipulated and studied by several methods. |
|
|
|
Initial methods to study DNA involved weight and shape, and used
sedimentation velocity, reassociation kinetics, and paper chromatography. The relatively
weak hydrogen bonds required for hybridization can be denatured ("melted") by
heat; C=G are stronger, thus melt at higher temperature and sediment faster. How
does highly repetitive DNA reassociate? Restriction endonucleases (cutter enzymes) are the
cornerstone for recombinant DNA technology. Fragments produced can be joined into
constructed microorganisms called "vectors" which are useful in transferring
genetic information to new cells. Radioactively labeled probes are DNA which complements a
particular target sequence of interest. A probe can be useful for disease diagnosis and
gene location. The polymerase chain reaction (PCR) allows a DNA template to be copied
millions of time. For example, using PCR, the DNA of a 120-million-years-old termite has
been mass reproduced, or amplified. There are many practical uses of recombinant DNA. |
|
|
|
|
|
|
| 23. |
Chromosome structure is hard to unravel. |
|
|
|
The human genome has approximately 3 billion base pairs, of which 1 to 2%
represents our 10 to 20 thousand genes. How do you pack this 2-m-long DNA into a nucleus
only 5 µm (5 millionths of a meter) in diameter? Chromosomes of eukaryotes are made up of
chromatin, which consists of nucleic acids and proteins. Eukaryotic DNA is sometimes
tightly coiled into heterochromatic regions which are protected from enzymatic action, and
genetically inactive. Euchromatic chromosome regions are considered to be active
genetically. Prokaryotic chromosomes are simpler, often naked, circular DNA or RNA, which
can still present a packing problem (e.g., the virus head). |
|
|
|
|
|
|
GENES ACT THROUGH A CHAIN OF EVENTS LEADING FROM DNA TO PROTEINS. |
|
|
|
|
|
| 24. |
The central dogma of molecular biology is DNA > mRNA >
polypeptide. |
|
|
|
Genetic information in the DNA template is transcribed to a short-lived
intermediate molecule, messenger RNA (mRNA), which is translated to the gene product, an
amino acid polymer (polypeptide), using an adapter molecule, transfer RNA (tRNA), to
decode the mRNA message. Other important players to know include RNA polymerase,
nucleoside triphosphates, and promoter sequences (transcription) and ribosomes
(translation). As with replication, transcription and translation involve initiation,
chain elongation, and termination. Among eukaryotes, transcription is in the nucleus,
translation in the cytoplasm; among prokaryotes, these processes are linked in time and
place, and are faster. Prokaryotic genes can be nested within other genes. Transfer RNA
helps understand some features of the genetic code (discussed earlier). The triplet code
is degenerate=redundant which is explained by the wobble hypothesis. Punctuation signals
are the termination codons (nonsense triplets). The triplet nature of the code was first
proven based on frameshift (nonsense) mutations, which lead to a change in the reading
frame of the mRNA, leading to premature chain termination. Organellar DNA (mitochondrion
and chloroplast) has a slightly different coding dictionary, suggesting that mitochondria
and chloroplasts are prokaryotic endosymbionts. (Experimental decoding and other aspects
of the code were described in #20.) |
|
|
|
|
|
|
| 25. |
Enzymes and other proteins determine the traits of the organism. |
|
|
|
Studies of inborn "errors of metabolism" show that inheritance
can be explained by enzyme alterations, which can be explained by gene alterations.
Enzymes reduce the energy of activation (help the rock go down the hill with a smaller
kick), and thus speed up chemical reactions in living organisms. Their structure
determines their function; a change in amino acid sequence leads to a change in structure,
which leads to a change in function, or lack of function. |
|
|
|
|
|
|
| 26. |
Metabolic pathways help explain how Mendelian alleles and genes
interact. |
|
|
|
A metabolic pathway is like a bucket brigade of several enzymes. Because
a diploid organism has two copies of each gene, and each gene can code for an enzyme, a
mutant allele coding for a defective enzyme can be unexpressed (recessive), due to the
presence of a normal allele coding for a functional enzyme. Metabolic pathways also
explain the phenomenon of epistasis, the nonreciprocal masking of one gene by another. If
different gene products (polypeptides) formulate enzymes needed at different points in the
pathway, a total defect in one enzyme may block the whole process. (A total defect might
represent a homozygous recessive or a hemizygous genotype.) This explains the
modification of Mendelian 9:3:3:1 ratios to 9:7, and 9:4:3 which we saw in segregating
maize seedlings, and the masking of eye color in Drosophila by the recessive white allele,
which is sex-linked. |
|
|
|
|
|
|
| 27. |
Protein structure helps explain how Mendelian alleles interact. |
|
|
|
There are four levels of protein structure. Some enzymes and other
proteins have quaternary structure (two or more polypeptide chains get together to make
the protein). As a result, we should say, "one gene, one polypeptide."
(When is this false?) The rules governing allelic relationships (e.g., dominance,
codominance) can be understood considering protein structure. Hemoglobin and collagen are
examples of proteins with quaternary structure; as a result, defective alleles can be
dominant. With monomeric proteins (e.g., many enzymes), a defective allele is often
recessive. Thus the concept of dominance is not a characteristic of the allele, but of
its product. Dominance is more arbitrary than that, because it depends on how we
define the trait; if our "trait" is the presence or absence of a polypeptide,
then all alleles are codominant. |
|
|
|
|
|
|
| 28. |
Genes are regulated by other genes. |
|
|
|
It would be energetically inefficient to have all genes transcribing and
translating "full-throttle". The lac operon of E. coli involves 3 structural
(enzyme-coding) genes and 2 regulatory genes, one an operator that "turns on"
the gene, and the other producing a repressor which binds with the operator. This system
allows the organism to produce the lactose-degrading enzymes when lactose is present.
Lactose changes the repressor (a diffusible substance) and prevents it from binding with
the operator, allowing the operator to be in the "on" position. Eukaryotes,
which have transcription and translation separate, involve intercellular substances such
as hormones which bind to receptor proteins, which then migrate into the nucleus.
Chromatin structure must be altered to expose DNA to transcription factors. This whole
process is sometimes called the regulatory cascade. Eukaryotes can have
post-transcriptional gene regulation. |
|
|
|
|
|
|
| 29. |
The frontier of biomedical genetics involves the immune system. |
|
|
|
Human antibodies, or immunoglobins, occur in millions of possible
combinations, and can respond selectively to invading chemicals and cells. The AIDS virus
has found a way to circumvent the body's immune system, and has its own system for rapidly
producing new genetic diversity, overcoming drugs and the body's defenses. Oncogenes,
which cause cancer, in some cases may represent regulatory proto-oncogenes which have
mutated to an "always on" position, therefore promoting unlimited cell growth. |
|
|
|
|
|
|
THE RESPONSIBLE APPLICATION OF GENETIC KNOWLEDGE IS SHARED BY ALL MEMBERS OF
SOCIETY. |
|
|
|
|
|
| 30. |
Genetics is a science; its main task is to discover knowledge. |
|
|
|
The scientific method places primary emphasis on collecting information
and refuting hypotheses. While the quest for knowledge places no restrictions on what
direction of research is appropriate, federal and state governments have an extremely
strong role in emphasizing what direction of research will be funded. Scientists have
ethical responsibilities, to their profession and to society. Thus there are rules and
incentives established by scientists, lawmakers, and administrative agencies to protect
human and animal subjects, to protect the environment, to share knowledge, and to
encourage the search for knowledge. I believe that the system is imperfect, but has many
opportunities for self-correction. |
|
|
|
|
|
|
| 31. |
The application of genetic knowledge can help us. |
|
|
|
Human health, nutrition, and biodiversity are some areas where genetic
knowledge, appropriately applied, has helped people live on earth. During the semester,
there will be several examples (see news articles) of major discoveries on genetic
conditions. Recent examples which have been in the news include discovery of genes for
late-onset Alzheimer's disease, colon cancer, and breast cancer. These provide hope to
those who suffer and to all of us, but the distance between a genetic link and a cure is
unknowingly far. |
|
|
|
|
|
|
| 32. |
The application of genetic knowledge can hurt us. |
|
|
|
In the 20th century in the United States, misguided efforts have used
genetic knowledge to discriminate against and harm people, based on their perceived
genetic inferiority. Some of these efforts arose not from politicians and poorly trained
outcasts of the scientific establishment, but through the advocacy of mainstream
scientists. While these practices are outrageous, and had contemporary critics, it is
easiest to pass judgment today. The instructor suggests a cautious approach to adopting
new technology, considering first the suffering and the rights of those most affected,
considering ourselves and "society" last. This could apply to aspects of
screening and remediation of genetic conditions affecting individuals and families. The
instructor also suggests that scientific knowledge is a changeable and growing area, and
the public should not assume that geneticists have any greater (or less) responsibility
for ethical choices, than the rest of humanity. |
|
|
|
|
|
|
|
|
|
|
