An Introduction to Genetic Analysis
Chapter 26
Evolutionary Genetics
Key Concepts
Evolution consists of continuous heritable change of organisms within a single line of descent
(phyletic evolution) and the differentiation between different lines of descent to form different
species (diversification).
The Darwinian mechanism of evolution rests on three principles: (1) organisms within a
species vary from one another, (2) the variation is heritable, and (3) different types leave
different numbers of offspring in future generations.
Both phyletic change and diversification are the result of the interaction between the
directional force of natural selection and random events.
Natural selection is the differential reproduction of different genotypes that is a consequence
of their different physiological, morphological, and behavioral traits.
Random effects include the sampling of gametes each generation in finite populations and the
random occurrence of mutations.
A consequence of the random factors in evolution is that the same forces of natural selection
do not lead to the same evolutionary result in independent lines of descent.
Species are reproductively isolated populations of organisms that can exchange genes within
the group but not with other species, because the groups are physiologically, behaviorally, or
developmentally incompatible.
Evolutionary novelties are possible because new DNA is acquired either by duplication and
subsequent differentiation of DNA already present in the species or by the introduction of
novel DNA from other species.
Introduction
The modern theory of evolution is so completely identified with the name of Charles Darwin
(1809–1882) that many people think that the concept of organic evolution was first proposed
by Darwin, but that is certainly not the case. Most scholars had abandoned the notion of fixed
species, unchanged since their origin in a grand creation of life, long before publication of
Darwin's The Origin of Species in 1859. By that time, most biologists agreed that new species
arise through some process of evolution from older species; the problem was to explain how
this evolution could occur.
Darwin's theory of the mechanism of evolution begins with the variation that exists among
organisms within a species. Individuals of one generation are qualitatively different from one
勇者并非无所畏惧, 而是判断出有比恐惧更重要的东西.
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An Introduction to Genetic Analysis
another. Evolution of the species as a whole results from the differential rates of survival and
reproduction of the various types, so the relative frequencies of the types change over time.
Evolution, in this view, is a sorting process.
For Darwin, evolution of the group resulted from the differential survival and reproduction of
individual variants already existing in the group—variants arising in a way unrelated to the
environment but whose survival and reproduction do depend on the environment.
MESSAGE
Darwin proposed a new explanation to account for the accepted phenomenon of
evolution. He argued that the population of a given species at a given time includes
individuals of varying characteristics. The population of the next generation will
contain a higher frequency of those types that most successfully survive and
reproduce under the existing environmental conditions. Thus, the frequencies of
various types within the species will change over time.
There is an obvious similarity between the process of evolution as Darwin described it and the
process by which the plant or animal breeder improves a domestic stock. The plant breeder
selects the highest-yielding plants from the current population and (as far as possible) uses
them as the parents of the next generation. If the characteristics causing the higher yield are
heritable, then the next generation should produce a higher yield. It was no accident that
Darwin chose the term natural selectionto describe his model of evolution through
differential rates of reproduction of different variants in the population. As a model for this
evolutionary process, he had in mind the selection that breeders exercise on successive
generations of domestic plants and animals.
We can summarize Darwin's theory of evolution through natural selection in three principles:
1. Principle of variation.Among individuals within any population, there is variation in
morphology, physiology, and behavior.
2. Principle of heredity.Offspring resemble their parents more than they resemble unrelated
individuals.
3. Principle of selection.Some forms are more successful at surviving and reproducing than
other forms in a given environment.
Clearly, a selective process can produce change in the population composition only if there
are some variations among which to select. If all individuals are identical, no amount of
differential reproduction of individuals can affect the composition of the population.
Furthermore, the variation must be in some part heritable if differential reproduction is to alter
the population's genetic composition. If large animals within a population have more
offspring than do small ones but their offspring are no larger on average than those of small
animals, then no change in population composition can occur from one generation to another.
Finally, if all variant types leave, on average, the same number of offspring, then we can
expect the population to remain unchanged.
勇者并非无所畏惧, 而是判断出有比恐惧更重要的东西.
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An Introduction to Genetic Analysis
MESSAGE
Darwin's principles of variation, heredity, and selection must hold true if there is to be
evolution by a variational mechanism.
The Darwinian explanation of evolution must apply to two different aspects of the history of
life. One is the successive change of form and function that occurs in a single continuous line
of descent time,phyletic evolution.Figure 26-1 shows such a continuous change over a period
of 40 million years in the size and curvature of the left shell of the oyster,Gryphea.The other
is thediversificationthat occurs among species: in the history of life on earth, there are many
different contemporaneous species having quite different forms and living in different ways.
Figure 26-2 shows some of the variety of bivalve mollusc forms that existed at various times
in the past 130 million years. Every species eventually becomes extinct and more than 99.9
percent of all the species that have ever existed are already extinct, yet the number of species
and the diversity of their forms and functions have increased in the past billion years. Thus
species not only must be changing, but must give rise to new and different species in the
course of evolution. Both of these processes are the consequences of heritable variation within
populations. Heritable variation provides the raw material for successive changes within a
species and for the multiplication of new species. The basic mechanisms of those changes (as
discussed in Chapter 24) are the origin of new variation by various kinds of mutational
mechanisms, the change in frequency of alleles by selective and random processes, the
possibility of divergence of isolated local populations because the selective forces are
different or because of random drift, and the reduction of variation between populations by
migration. From those basic mechanisms, population genetics, as discussed in Chapter 24,
derives a set of principles governing changes in the genetic composition of populations. The
application of these principles of population genetics provides an articulated theory of
evolution.
MESSAGE
Evolution, under the Darwinian scheme, is the conversion of heritable variation
between individuals within populations into heritable differences between populations
in time and in space, by population genetic mechanisms.
A synthesis of forces: variation and divergence of populations
In evolution, the various forces of breeding structure, mutation, migration, and selection are
all acting simultaneously in populations. We need to consider how these forces, operating
together, mold the genetic composition of populations to produce both variation within local
populations and differences between them.
The genetic variation within and between populations is a result of the interplay of the various
evolutionary forces (Figure 26-3). Generally, as Table 26-1 shows, forces that increase or
maintain variation within populations prevent the differentiation of populations from each
other, whereas the divergence of populations is a result of forces that make each population
勇者并非无所畏惧, 而是判断出有比恐惧更重要的东西.
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An Introduction to Genetic Analysis
homozygous. Thus, random drift (or inbreeding) produces homozygosity while causing
different populations to diverge. This divergence and homozygosity are counteracted by the
constant flux of mutation and the migration between localities, which introduce variation into
the populations again and tend to make them more like each other.
When Darwin arrived in the Galapagos Islands in 1835 he found a remarkable group of
finchlike birds that provided a very suggestive case for the development of his theory of
evolution. The Galapagos archipelago is a cluster of 29 islands and islets of different sizes
lying on the equator about 600 miles off the coast of Ecuador. Figure 26-4 shows the 13
Galapagos finch species. Finches are generally ground-feeding seed eaters with stout bills for
cracking the tough outer coats of the seeds. The Galapagos species, though clearly finches,
have an immense variation in how they make a living and in their bill shapes and their
behaviors, which underly these ecological differences. For example, the vegetarian tree finch
eats fruits and leaves, the insectivorous finch has a bill with a biting tip for eating large insects,
and, most remarkable of all, the woodpecker finch grasps a twig in its beak and uses it to
obtain insect prey by probing holes in trees. This diversity of species arose from an original
population of a seed-eating finch that arrived in the Galapagos from the mainland of South
America and populated the islands. The descendants of the original colonizers spread to the
different islands and to different parts of large islands and formed local populations that
diverged from each other and eventually formed different species.
Consider the situation at a genetically variable locus in a group of isolated island populations
that were founded by migrants from an initial single population. The original founders of each
population are small samples from the donor population and so differ from each other in allele
frequencies because of a random sampling effect. This initial variation is called the founder
effect. In succeeding generations, as a result of random genetic drift within each population,
there is a further change in allelic frequency, pi of each of the i alleles toward either 1 or 0, but
average allelic frequency over all such populations remains pi. Figure 26-5 shows the
distribution of allelic frequencies among islands in successive generations, where p(A1) =
0.5. In generation 0, all populations are identical. As time goes on, the gene frequencies
among the populations diverge and some become fixed. After about 2N generations, every
allelic frequency except the fixed classes (p = 0 and p = 1) is equally likely, and about half the
populations are totally homozygous. By the time 4N generations have gone by, 80 percent of
the populations are fixed, half being homozygous A/A and half being homozygous a/a.
The process of differentiation by inbreeding in island populations is slow, but not on an
evolutionary or geological time scale. If an island can support, say, 10,000 individuals of a
rodent species, then, after 20,000 generations (about 7000 years, assuming 3 generations per
year), the population will be homozygous for about half of all the loci that were initially at the
maximum of heterozygosity. Moreover, the island will be differentiated from other similar
islands in two ways. For the loci that are fixed, many of the other islands will still be
segregating, and others will be fixed at a different allele. For the loci that are still segregating
in all the islands, there will be a large variation in gene frequency from island to island, as
shown in Figure 26-5.
勇者并非无所畏惧, 而是判断出有比恐惧更重要的东西.
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An Introduction to Genetic Analysis
Any population of any species is finite in size, so all populations should eventually become
homozygous and differentiated from one another as a result of inbreeding. Evolution would
then cease. In nature, however, new variation is always being introduced into populations by
mutation and by some migration between localities. Thus, the actual variation available for
natural selection is a balance between the introduction of new variation and its loss through
local inbreeding. The rate of loss of heterozygosity in a closed population is 1/(2N) per
generation, so any effective differentiation between populations will be negated if new
variation is introduced at this rate or a higher rate. If m is the migration rate into a given
population and μ is the rate of mutation to new alleles per generations, then roughly (to an
order of magnitude) a population will retain most of its heterozygosity and will not
differentiate much from other populations by local inbreeding if
For populations of intermediate and even fairly large size, it is unlikely that Nμ ≥ 1. For
example, if the population size is 100,000, then the mutation rate must exceed 10−5, which is
somewhat on the high side for known mutation rates, although it is not an unknown rate. On
the other hand, a migration rate of 10−5 per generation is not unreasonably large. In fact
Thus, the requirement that Nm ≥ 1
is equivalent to the requirement that
irrespective of population size. For many populations, more than a single migrant individual
per generation is quite likely. Human populations (even isolated tribal populations) have a
higher migration rate than this minimal value, and, as a result, no locus is known in humans
for which one allele is fixed in some populations and an alternative allele is fixed in others
(Table 26-2).
The effects of selection are more variable. Directional selection pushes a population toward
homozygosity, rejecting most new mutations as they are introduced but occasionally (if the
mutation is advantageous) spreading a new allele through the population to create a new
homozygous state. Whether such directional selection promotes differentiation of populations
depends on the environment and on chance events. Two populations living in very similar
environments may be kept genetically similar by directional selection, but, if there are
environmental differences, selection may direct the populations toward different
compositions.
勇者并非无所畏惧, 而是判断出有比恐惧更重要的东西.
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An Introduction to Genetic Analysis
Selection favoring heterozygotes (balancing selection) will, for the most part, maintain more
or less similar polymorphisms in different populations. However, again, if the environments
are different enough between them, then the populations will show some divergence. The
opposite of balancing selection is selection against heterozygotes, which produces unstable
equilibria. Such selection will cause homozygosity and divergence between
populations.
Multiple adaptive peaks
We must avoid taking an overly simplified view of the consequences of selection. At the level
of the gene—or even at the level of the partial phenotype—the outcome of selection for a trait
in a given environment is not unique. Selection to alter a trait (say, to increase size) may be
successful in a number of ways. In 1952, F. Robertson and E. Reeve successfully selected to
change wing size in Drosophila in two different populations. However, in one case, the
number of cells in the wing changed, whereas, in the other case, the size of the wing cells
changed. Two different genotypes had been selected, both causing a change in wing size. The
initial state of the population at the outset of selection determined which of these selections
occurred.
The way in which the same selection can lead to different outcomes can be most easily
illustrated by a simple hypothetical case. Suppose that the variation of two loci (there will
usually be many more) influences a character and that (in a particular environment)
intermediate phenotypes have the highest fitness. (For example, newborn babies have a higher
chance of surviving birth if they are neither too big nor too small.) If the alleles act in a simple
way in influencing the phenotype, then the three genetic constitutions AB/ab, Ab/Ab, and
aB/aB will produce a high fitness because they will all be intermediate in phenotype. On the
other hand, very low fitness will characterize the double homozygotes AB/AB and ab/ab.
What will the result of selection be? We can predict the result by using the mean fitness of
a population. As previously discussed, selection acts in most simple cases to increase
Therefore, if we calculate for every possible combination of gene frequencies at the two
loci, we can determine which combinations yield high values of Then we should be able to
predict the course of selection by following a curve of increasing .
The surface of mean fitness for all possible combinations of allelic frequency is called an
adaptive surface or an adaptive landscape (Figure 26-6). The figure is like a topographic map.
The frequency of allele A at one locus is plotted on one axis, and the frequency of allele B at
the other locus is plotted on the other axis. The height above the plane (represented by
topographic lines) is the value of
that the population would have for a particular
combination of frequencies of A and B. According to the rule of increasing fitness, selection
should carry the population from a low-fitness “valley” to a high-fitness “peak.” However,
Figure 26-6 shows that there are two adaptive peaks, corresponding to a fixed population of
Ab/Ab and a fixed population of aB/aB, with an adaptive valley between them. Which peak
the population will ascend—and therefore what its final genetic composition will
be—depends on whether the initial genetic composition of the population is on one side or the
other of the dashed “fall line” shown in the figure.
勇者并非无所畏惧, 而是判断出有比恐惧更重要的东西.
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An Introduction to Genetic Analysis
MESSAGE
Under identical conditions of natural selection, two populations may arrive at two
different genetic compositions as a direct result of natural selection.
It is important to note that nothing in the theory of selection requires that the different
adaptive peaks be of the same height. The kinetics of selection is such that increases, not
that it necessarily reaches the highest possible peak in the field of gene frequencies. Suppose,
for example, that a population is near the peak aB/aB in Figure 26-6 and that this peak is
lower than the Ab/Ab peak. Selection alone cannot carry the population to Ab/Ab, because that
would require a temporary decrease in as the population descended the aB/aB slope,
crossed the saddle, and ascended the other slope. Thus, the force of selection is myopic. It
drives the population to a local maximum of in the field of gene frequencies—not to a
global one.
The existence of multiple adaptive peaks for a selective process means that some differences
between species are the result of history and not of environmental differences. For example,
African rhinoceroses have two horns, and Indian rhinoceroses have one (Figure 26-7). We
need not invent a special story to explain why it is better to have two horns on the African
plains and one in India. It is much more plausible that the trait of having horns was selected
but that two long, slender horns and one short, stout horn are simply alternative adaptive
features, and historical accident differentiated the species. Explanations of adaptations by
natural selection do not require that every difference between species be differentially
adaptive.
Exploration of adaptive peaks
Random and selective forces should not be thought of as simple antagonists. Random drift
may counteract the force of selection, but it can enhance it as well. The outcome of the
evolutionary process is a result of the simultaneous operation of these two forces. Figure 26-8
illustrates these possibilities. Note that there are multiple adaptive peaks in this landscape.
Because of random drift, a population under selection does not ascend an adaptive peak
smoothly. Instead, it takes an erratic course in the field of gene frequencies, like an
oxygen-starved mountain climber. Pathway I shows a population history where adaptation has
failed. The random fluctuations of gene frequency were sufficiently great that the population
by chance became fixed at an unfit genotype. In any population, some proportion of loci are
fixed at a selectively unfavorable allele because the intensity of selection is insufficient to
overcome the random drift to fixation. The existence of multiple adaptive peaks and the
random fixation of less fit alleles are integral features of the evolutionary process. Natural
selection cannot be relied on to produce the best of all possible worlds.
Pathway II in Figure 26-8, on the other hand, shows how random drift may improve
adaptation. The population was originally in the sphere of influence of the lower adaptive
peak; however, by random fluctuation in gene frequency, its composition passed over the
adaptive saddle, and the population was captured by the higher, steeper adaptive peak. This
passage from a lower to a higher adaptive stable state could never have occurred by selection
勇者并非无所畏惧, 而是判断出有比恐惧更重要的东西.
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An Introduction to Genetic Analysis
in an infinite population, because, by selection alone,
cross from one slope to another.
could never decrease temporarily to
An important source of indeterminacy in the outcome of a long selective process is the
randomness of the mutational process. After the initial genetic variation is exhausted by the
selective and random fixation of alleles, new variation arises from mutation that can be the
source of yet further evolutionary change. The particular direction of this further evolution
depends on the particular mutations that occur and the time order in which they take place. A
very clear illustration of this historical contingency of the evolutionary process is the selection
experiment of H. Wichman and her colleagues to allow the bacteriophage ΦX174 to
reproduce at high temperatures and to change its host from Escherichia coli to Salmonella
typhimurium. Two independent selection lines were established and both evolved both the
temperature and the host change. In one of the two lines, the ability to reproduce on E. coli
still existed, but, in the other line, the ability was lost. The bacteriophage has only 11 genes,
and the successive changes in the DNA for all these genes and in the proteins encoded by
them were recorded during the selection process. The result for the two strains is shown in
Table 26-3. There were 15 DNA changes in strain TX, located in 6 different genes; in strain
ID, there were 14 changes in 4 of the genes. The strains had identical changes in only 7 cases,
including a large deletion, but the temporal order of these identical changes differed between
the lines. So, for example, the change at DNA site 1533, causing a substitution of isoleucine
for threonine, was the third change in the ID strain, but the fourteenth change in the TX strain.
Heritability of variation
The first rule of any reconstruction or prediction of evolution is that the phenotypic variation
must be heritable. It is easy to construct stories of the possible selective advantage of one
form of a trait over another, but it is a matter of considerable experimental difficulty to show
that the variation in the trait corresponds to genotypic differences (see Chapter 25).
It should not be supposed that all variable traits are heritable. Certain metabolic traits (such as
resistance to high salt concentrations in Drosophila) show individual variation but no
heritability. In general, behavioral traits have lower heritabilities than morphological traits,
especially in organisms with more complex nervous systems that exhibit immense individual
flexibility in central nervous states. Before any judgment can be made about the evolution of a
particular quantitative trait, it is essential to determine if there is genetic variance for it in the
population whose evolution is to be predicted. Thus, suggestions that such traits in the human
species as performance on IQ tests, temperament, and social organization are in the process of
evolving or have evolved at particular epochs in human history depend critically on evidence
about whether there is genetic variation for these traits. Reciprocally, traits that appear to be
completely invariant in a species may nevertheless evolve.
One of the most important findings in evolutionary genetics has been the discovery of
substantial genetic variation underlying characters that show no morphological variation!
These are called canalized characters, because the final outcome of their development is
held within narrow bounds despite disturbing forces. Development is such that all the
different genotypes for canalized characters have the same constant phenotype over the range
勇者并非无所畏惧, 而是判断出有比恐惧更重要的东西.
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An Introduction to Genetic Analysis
of environments that is usual for the species. The genetic differences are revealed if the
organisms are put in a stressful environment or if a severe mutation stresses the
developmental system. For example, all wild-type Drosophila have exactly four scutellar
bristles (Figure 26-9). If the recessive mutant scute is pres-ent, the number of bristles is
reduced, but, in addition, there is variation from fly to fly. This variation is heritable, and lines
with zero or one bristle and lines with three or four bristles can be obtained by selection in the
presence of the scute mutation. When the mutation is removed, these lines now have two and
six bristles, respectively. Similar experiments have been performed by using extremely
stressful environments in place of mutants. A consequence of such hidden genetic variation is
that a character that is phenotypically uniform in a species may nevertheless undergo rapid
evolution if a stressful environment uncovers the genetic variation.
Observed variation within and between populations
In Chapter 24, the existence of genetic variation within populations at the levels of
morphology, karyotype, proteins, and DNA were documented. The general conclusion is that
about one-third of all protein-encoding loci are polymorphic and that all classes of DNA,
including exons, introns, regulatory sequences, and flanking sequences, show nucleotide
diversity among individuals within populations. Several of these examples also documented
some differences in the genotype frequencies between populations (see Tables 24-1 through
24-3, 24-5, and 24-7). The relative amounts of variation within and between populations vary
from species to species, depending on history and environment. In humans, some gene
frequencies (for example, those for skin color or hair form) are well differentiated between
populations and major geographical groups (so-called geographical races). If, however, we
look at single structural genes identified immunologically or by electrophoresis rather than by
these outward phenotypic characters, the situation is rather different. Table 26-2 shows the
three loci for which Caucasians, Negroids, and Mongoloids are known to be most different
from one another (Duffy and Rhesus blood groups and the P antigen) compared with the three
polymorphic loci for which the races are most similar (Auberger blood group and Xg and
secretor factors). Even for the most divergent loci, no race is homozygous for one allele that is
absent in the other two races.
In general, different human populations show rather similar frequencies for polymorphic
genes. Figure 26-10 is a triallelic diagram for the three main allelic classes, IA, IB, and i, of
the ABO blood group. Each point represents the allelic composition of a population, where
the three allelic frequencies can be read by taking the lengths of the perpendiculars from each
side to the point. The diagram shows that all human populations are bunched together in the
region of high i, intermediate IA, and low IB frequencies. Moreover, neighboring points
(enclosed by dashed lines) do not correspond to geographical races, so such races cannot be
distinguished from one another by characteristic allelic frequencies for this gene. The study of
polymorphic blood groups and enzyme loci in a variety of human populations has shown that
about 85 percent of total human genetic diversity is found within local populations, about 7
percent is found among local populations within major geographical races, and the remaining
8 percent is found among major geographical races. Clearly, the genes influencing skin color,
hair form, and facial form that are well differentiated among races are not a random sample of
structural gene loci.
勇者并非无所畏惧, 而是判断出有比恐惧更重要的东西.
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An Introduction to Genetic Analysis
Process of speciation
When we examine the living world we see that individual organisms are usually clustered into
collections that resemble each other more or less closely and are clearly distinct from other
clusters. A close examination of a sibship of Drosophila will show differences in bristle
number, eye size, and details of color pattern from fly to fly, but an entomologist has no
difficulty whatsoever in distinguishing Drosophila melanogaster from, say, Drosophila
pseudoobscura. One never sees a fly that is halfway between these two kinds. Clearly, in
nature at least, there is no effective interbreeding between these two forms. A group of
organisms that exchanges genes within the group but cannot do so with other groups is what
is meant by a species. Within a species there may exist local populations that are also easily
distinguished from one another by some phenotypic characters, but it is also the case that
genes can easily be exchanged between them. Thus, no one has any difficulty distinguishing a
“typical” Senegalese from a “typical” Swede, but, as a consequence of the migration and
mating history of humans in North America in the past 300 years, an immense number of
people exist of every degree of intermediacy between these local geographical types. They are
not separate species. A geographically defined population that is genetically distinguishable
from other local populations but is capable of exchanging genes with those other local
populations is sometimes called a geographical race. For example, in regard to the land snail
Cepaea nemoralis, whose shell color and banding polymorphism was described in Chapter 24,
there is a high frequency of albino shells in the Pyrenees at the higher elevations, but nowhere
else; so we can distinguish a Pyrenees “race” of Cepaea.In general, there is some difference in
the frequency of various genes in different geographical populations of a species, so the
marking out of a particular population as a distinct race is arbitrary and, as a consequence, the
concept of race is no longer much used in biology.
MESSAGE
A species is a group of organisms that can exchange genes among themselves but are
genetically unable to exchange genes in nature with other such groups. A
geographical race is a phenotypically distinguishable local population within a species
that is capable of exchanging genes with other races within that species. Because
nearly all geographical populations are different from others in the frequencies of
some genes, race is a concept that makes no clear biological distinction.
All the species now existing are related to each other by common ancestors at various times in
the evolutionary past. That means that each of these species has separated out from a
previously existing species and has become genetically distinct and genetically isolated from
its ancestral line. In extraordinary circumstances, the founding of such a genetically isolated
group might occur by a single mutation, but the carrier of that mutation would need to be
capable of self-fertilization or vegetative reproduction. Moreover, that mutation would have to
cause complete mating incompatibility between its carrier and the original species and to
allow the new line to compete successfully with the previously established group. Although
not impossible, such events must be rare.
The usual pathway to the formation of new species is through geographical races. As stated
earlier in this chapter, populations that are geographically separated will diverge from each
勇者并非无所畏惧, 而是判断出有比恐惧更重要的东西.
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An Introduction to Genetic Analysis
other genetically as a consequence of a combination of unique mutations, selection, and
genetic drift. Migration between populations will prevent them from diverging too far,
however. As shown on page 778, even a single migrant per generation will be sufficient to
prevent populations from fixing at alternative alleles by genetic drift alone, and even selection
toward different adaptive peaks will not succeed in causing complete divergence unless it is
extremely strong. As a consequence, populations that diverge enough to become new,
reproductively isolated species must first be virtually totally isolated from each other by some
mechanical barrier. This isolation almost always requires some spatial separation, and the
separation must be great enough or the natural barriers to the passage of migrants must be
strong enough to prevent any effective migration. Such populations are referred to as
allopatric. The isolating barrier might be, for example, the extending tongue of a continental
glacier during glacial epochs that forces apart a previously continuously distributed
population, or the drifting apart of continents that become separated by water, or the
infrequent colonization of islands that are far from shore. The critical point is whether the
mechanisms of dispersal of the original species will make further migration between the
separated populations a very rare event. If so, then the populations are now genetically
independent and will continue to diverge by mutation, selection, and genetic drift. Eventually,
the genetic differentiation between the populations becomes so great that the formation of
hybrids between them would be physiologically, developmentally, or behaviorally impossible
even if the geographical separation were abolished. These biologically isolated populations
are now new species, formed by the process of allopatric speciation.
MESSAGE
Allopatric speciation occurs through an initial geographical and mechanical isolation
of populations that prevents any gene flow between them, followed by genetic
divergence of the isolated populations sufficient to make it biologically impossible for
them to exchange genes in the future.
The forms of biological isolating mechanisms that arise between species include:
1. Prezygotic isolation: failure to form zygotes
a. Lack of mating opportunity
i. Temporal isolation: activity, fertility, or mating at different times or seasons
ii. Ecological isolation: restriction to different, nonoverlapping habitats or ecological niches
b. Lack of mating compatability
i. Sexual, psychological, or behavioral incompatibility
ii. Mechanical isolation: the failure of genitalia or flower parts to match
iii. Gametic isolation: physiological incompatibility of sperm with the reproductive tract of
the female in animals or of the pollen with the style in plants or a failure of successful
fertilization of the egg cell or ovule
勇者并非无所畏惧, 而是判断出有比恐惧更重要的东西.
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An Introduction to Genetic Analysis
Examples of prezygotic isolating mechanisms are well known in plants and animals. The two
species of pine growing on the Monterey peninsula, Pinus radiata and P. muricata, shed their
pollen in February and April and so do not exchange genes. The light signals that are emitted
by male fireflies and attract females differ in intensity and timing between species. In the
tsetse fly, Glossina, mechanical incompatabilities cause severe injury and even death if males
of one species mate with females of another. The pollen of different species of Nicotiana, the
genus to which tobacco belongs, either fail to germinate or cannot grow down the style of
other species.
2. Postzygotic isolation: failure of fertilized zygote to contribute gametes to future generations
a. Hybrid inviability: hybrids either fail to develop or have a lower fitness than individuals of
the parental species
b. Hybrid sterility: partial or complete inability of adult hybrids of either sex to produce
gametes in normal numbers
c. Hybrid breakdown: sterility or inviability of the offspring of matings among hybrids or
between hybrids and the parental species
Postzygotic isolation is more common in animals than in plants, apparently because the
development of many plants is much more tolerant to genetic incompatabilities and
chromosomal variations. When the eggs of the leopard frog, Rana pipiens, are fertilized by
sperm of the wood frog, R. sylvatica, the embryos do not succeed in developing. Horses and
asses can easily be crossed to produce mules, but, as is well known, these hybrids are sterile.
Genetics of species isolation
Usually, it is not possible to carry out any genetic analysis of the isolating mechanisms
between two species for the simple reason that, by definition, they cannot be crossed with
each other. It is possible, however, to make use of very closely related species in which the
isolating mechanism is an incomplete hybrid sterility and hybrid breakdown. Then,
segregating progeny of hybrid F2 or backcross generations can be analyzed by using genetic
markers. An example is shown in Figure 26-11. Drosophila pseudoobscura and D. persimilis
are closely related species that never exchange genes in nature but can be crossed in the
laboratory. The F1 males are completely sterile, but the F1 females have normal fertility and
can be backcrossed to males of the parental species. A manifestation of hybrid male sterility is
that, in the cross between D. persimilis females and D. pseudoobscura males, the testes of F1
males are about one-fifth normal size. Genetically marking the chromosomes with visible
mutants and backcrossing F1 females to males of either species permits every combination of
X chromosomes and autosomes to be identified and their effects on testis size to be
determined. As Figure 26-11 shows, when an X chromosome from one species is present
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An Introduction to Genetic Analysis
together with a complete diploid set of autosomes from the other species, the testes are at a
minimum. As individual autosomes of the species to which the X chromosome belongs are
substituted, the testis size increases, up to a complete haploid set of compatible autosomes but
not beyond that. There is also evidence (not shown) of an interaction between the source of
the cytoplasm and the X chromosome.
When such marker experiments have been performed on other species, mostly in the genus
Drosophila, the general conclusions are that gene differences responsible for hybrid
inviability are on all the chromosomes more or less equally and that, for hybrid sterility, there
is some added effect of the X chromosome. For behavioral sexual isolation, the results are
variable. In Drosophila, all the chromosomes are involved, but, in Lepidoptera, the genes are
much more localized, apparently because specific pheromones are involved. The sex
chromosome has a very strong effect in butterflies; in the European corn borer, only three loci,
one of which is on the sex chromosome, account for the entire isolation between pheromonal
races.
Origin of new genes
It is clear that evolution consists of more than the substitution of one allele for another at loci
of defined function. New functions have arisen that have resulted in major new radiations of
ways of making a living. Many of these new functions—for example, the development of the
mammalian inner ear from a transformation of the reptilian jaw bones, result from continuous
transformations of shape for which we do not have to invoke totally new genes and proteins.
But qualitative novelties arise at the level of genes and proteins, such as the origination of
photosynthesis in plants, of cell walls, of contractile proteins, of a variety of cell and tissue
types, of oxygenation molecules such as hemoglobin, of the immune system, of chemical
detoxification cycles, and of digestive enzymes. Older metabolic functions must have
necessarily been maintained while new ones were being developed, which in turn means that
old genes had to be preserved while new genes with new functions had to evolve. Where does
the DNA for new functions come from?
Polyploidy
One process for the provision of new DNA is the duplication of the entire genome by
polyploidization, much more common in plants than in animals (see Chapter 18). The
evidence that polyploids have played a major role in the evolution of plant species is shown in
Figure 26-12, which shows the frequency distribution of haploid chromosome numbers
among dicotyledonous plant species. Above a chromosome number of about 12, even
numbers are much more common than odd numbers—a consequence of frequent
polyploidy.
Duplications
A second process for the increase in DNA is the duplication of small sections of the genome
as a consequence of misreplication of DNA (Chapter 16). At first, after a duplicated segment
has arisen, there is the possibility of an increase in the production of the polypeptide, but then
functional differentiation between the sequences may occur in one of two directions. In one,
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An Introduction to Genetic Analysis
no functional change occurs and there is simply a duplication of polypeptide production. The
general function of the original sequence is maintained in the new DNA, but there is some
differentiation of the sequences by accumulated mutations so that variations on the same
protein theme are produced, allowing a somewhat more complex molecular structure. A
classic example is the set of gene duplications and divergences that underlie the production of
human hemoglobin. Adult hemoglobin is a tetramer consisting of two α polypeptide chains
and two β chains, each with its bound heme molecule. The gene encoding the α chain is on
chromosome 16 and the gene for the β chain is on chromosome 11, but the two chains are
about 49 percent identical in their amino acid sequences, an identity that clearly points to the
common origin. However, in fetuses, until birth, about 80 percent of β chains are substituted
by a related γ chain. These two polypeptide chains are 75 percent identical, and the gene for
the γ chain is close to the β-chain gene on chromosome 11 and has an identical intron-exon
structure. This developmental change in globin synthesis is part of a larger set of
developmental changes that are shown in Figure 26-13. The early embryo begins with α, γ, ε,
and ζ chains and, after about 10 weeks, the ε and ζ are replaced by α, β, and γ. Near birth, β
replaces γ and a small amount of yet a sixth globin, δ, is produced.
Table 26-4 shows the percentage of amino acid identity among these chains, and Figure 26-14
shows the chromosomal locations and intron-exon structures of the genes encoding them. The
story is remarkably consistent. The β, δ, γ, and ε chains all belong to a “β-like” group; they
have very similar amino acid sequences and are encoded by genes of identical intron-exon
structure that are all contained in a 60-kb stretch of DNA on chromosome 11. The α and ζ
chains belong to an “α-like” group and are encoded by genes contained in a 40-kb region on
chromosome 16. Two slightly different forms of the α chain are encoded by neighboring
genes with identical intron-exon structure, as are two forms of the ζ chain. In addition, Figure
26-14
α
β. These pseudogenes are duplicate copies of the genes that did not acquire new
functions but accumulated random mutations that render them nonfunctional. At every
moment in development, hemoglobin molecules consist of two chains from the “α-like” group
and two from the “β-like” group, but the specific members of the groups change in embryonic,
fetal, and newborn life. What is even more remarkable is that the order of genes on each
chromosome is the same as the temporal order of appearance of the globin chains in the
course of development. This complexity of chain replacement evolved in mammals and is not
present in fish, reptiles, birds, and monotremes, which have only the basic α,β system. Figure
26-15 shows the order of origin of the different components of the β-like system.
In the evolution of hemoglobin, the duplicated DNA encodes a function closely related to that
served by the original gene from which it arose. The other possibility for evolution of
duplicated DNA is a complete qualitative divergence in function. An example of such a
divergence is shown in Figure 26-16. Birds and mammals, like other eukaryotic organisms,
have a gene encoding lysozyme, a protective enzyme that breaks down the cell wall of
bacteria. This gene has been duplicated in mammals to produce a second sequence that
encodes a completely different, nonenzymatic protein, α-lactalbumin. Figure 26-16 shows that
the duplicated gene has the same intron-exon structure as that of the lysozyme gene, whose
array of four exons and three introns itself suggests an earlier multiple duplication event in the
origin of lysozyme.
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An Introduction to Genetic Analysis
Imported DNA
New DNA that is the basis of new functions does not arise only from the duplication of DNA
at an adjacent chromosomal location. Repeatedly in evolution, extra DNA has been imported
into the genome from outside sources by mechanisms other than normal sexual reproduction.
DNA can be inserted into chromosomes from other chromosomal locations and from other
species, and genes from totally unrelated organisms can become incorporated into cells to
become part of their heredity and function.
Cellular organelles.
Eukaryotic cells contain cellular organelles such as mitochondria or the chloroplasts of
photosynthetic organisms. Both of these organelles are the descendants of prokaryotes that
entered the eukaryotic cells either as infections or from being ingested. These prokaryotes
became symbionts, transferring much of their genome to the nuclei of their eukaryotic hosts
but retaining genes that are essential to cellular functions. Mitochondria have retained about
three dozen genes concerned with cellular respiration as well as some tRNA genes, whereas
chloroplast genomes have about 130 genes encoding enzymes of the photosynthetic cycle as
well as ribosomal proteins and tRNAs.
Important evidence for the extracellular origin of mitochondria is in their genetic code. The
“universal” DNA–RNA code of nuclear genes is not, in fact, universal and differs in some
respects from that in mitochondria. Table 26-5 shows that, for 6 of the 64 RNA triplets,
mitochondria differ in their coding from the nuclear genome. Moreover, mitochondria in
different organisms differ from each other for these coding elements, providing evidence that
the invasion of eukaryotic cells by prokaryotes must have occurred at least five times, each
time from a prokaryote with a different coding system. For the vertebrates, worms, and insects,
the mitochondrial code is more regular than the universal nuclear code. In the nuclear genome,
isoleucine is the only threefold redundantly coded amino acid, with methionine being coded
by the fourth member of the codon group, separated by a transition from A to G; whereas, in
mitochondria, there are two methionines separated by a transversion from the two isoleucines
in this group.
Horizontal transfer.
It is now clear that the nuclear genome is open to the insertion of DNA both from other parts
of the same genome and from outside (see Chapter 20). The chromosomes of an individual
Drosophila, for example, contain a large variety of families of transposable elements with
multiple copies of each distributed around the genome. As much as 25 percent of the DNA of
Drosophila may be of transposable origin. It is not clear at present what role this mobile DNA
plays in functional evolution. The transposition that occurs when transposable elements are
introduced into zygotes at mating, as in the P elements of Drosophila, results in an explosive
proliferation of the elements in the recipient genome. When a mobile element is inserted into
a gene, the resulting mutation usually has a drastic deleterious effect on the organism, but this
effect may be an artifact of the methods used to detect the presence of such elements.
Laboratory selection experiments on quantitative characters have shown that transposition can
act as an added source of selectable variation. Finally, there is the possibility that genes are
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An Introduction to Genetic Analysis
transferred from the nuclear genome of one species to the nuclear genome of another by the
phenomenon of retrotransposition mediated by retroviruses (see Chapter 20). This possibility
could be a powerful source of the acquisition of new functions by a species because such
retroviruses could be carried between very distantly related species by common disease
vectors such as insects or by bacterial infections.
Relation of genetic to functional change
There is no simple relation between the amount of change in DNA and how much functional
change occurs in the encoded protein. At one extreme, almost the entire amino acid sequence
of a protein can be replaced while maintaining the original function. Eukaryotes, from yeast to
humans, produce an enzyme, lysozyme, that breaks down bacterial cell walls. In the
evolutionary divergence that has occurred in the yeast and vertebrate lines since their descent
from an ancient common ancestor, virtually every amino acid in this protein has been replaced;
so an alignment of their two protein or DNA sequences would not reveal any similarity. The
evidence that they are descended from an original common ancestral gene comes from
comparisons of evolutionarily intermediate forms that show more and more divergence of
sequence as species are more divergent. The maintenance of the function despite the
replacement of the amino acids has been the result of the maintenance of the
three-dimensional structure of the enzyme by the selective substitutions of just the right
amino acids to maintain shape.
In contrast, it is possible to change the function of an enzyme by a single amino acid
substitution. The sheep blow fly, Lucilia cuprina, has developed resistance to
organophosphate insecticides used widely to control it. R. Newcombe, P. Campbell, and their
colleagues showed that this resistance is the consequence of a single substitution of an
aspartic acid for a glycine in the active site of an enzyme that ordinarily is a carboxylesterase.
The mutation causes complete loss of the carboxylesterase activity and its replacement by
esterase specificity. A three-dimensional modeling of the molecule indicates that the change is
the result of the ability of the substituted protein to bind a water molecule close to the site of
attachment of the organophosphate, which is then hydrolyzed by the water.
MESSAGE
There is no regular relation between how much DNA change takes place in evolution
and how much functional change results.
When more than one mutation is required for the origin of a new function, the order in which
these mutations occur in the evolution of the molecule may be critical. B. Hall has
experimentally changed a gene to a new function in E. coli by a succession of mutations and
selection. In addition to the lacZ genes specifying the usual lactose-fermenting activity in E.
coli, another structural gene locus, ebg, specifies another β-galactosidase that does not
ferment lactose, although it is induced by lactose. The natural function of this second gene is
unknown. Hall was able to mutate and select this extra gene to enable E. coli to live, without
any lactose, on a wholly new substrate, galactobionate. To do so, he first had to mutate the
regulatory sequence of ebg so that it was constitutive and no longer required lactose to induce
its translation. Next, he tried to select mutants that would ferment lactobionate, but he failed.
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An Introduction to Genetic Analysis
First, it was necessary to select a form that would ferment a related substrate, lactulose, and
then the lactulose fermenters could be mutated and selected to operate on lactobionate.
Moreover, only some of the independent mutants from lactose fermentation to lactulose
utilization could be further mutated and selected to operate on lactobionate. The others were
dead ends. Thus, the sequence of evolution had to be (1) from an inducible to a constitutive
enzyme, followed by (2) just the right mutation from lactose to lactulose fermentation,
followed by (3) a mutation to ferment lactobionate.
MESSAGE
In the evolution of new functions by mutation and selection, there are particular
pathways through the array of mutations that must be followed. Other pathways come
to dead ends that do not allow further evolution.
Rate of molecular evolution
Although it is possible that only one or a few mutations lead to a change in the specificity of a
protein, the more usual situation is that DNA accumulates substitutions over long periods of
evolution without making a qualitative change in the functional properties of the proteins that
are encoded. There may, however, be smaller effects influencing the kinetic properties, timing
of production, or quantities of the encoded proteins that, in turn, will affect the fitness of the
organism that carries them. Mutations of DNA can have three effects on fitness. First, they
may be deleterious, reducing the probability of survival and reproduction of their carriers. All
of the laboratory mutants used by the experimental geneticist have some deleterious effect on
fitness. Second, they may actually increase fitness by providing increased efficiency or by
expanding the range of environmental conditions in which the species can make a living or by
enabling the organism to track changes in the environment. Third, they may have no effect on
fitness, leaving the probability of survival and reproduction unchanged; they are the so-called
neutral mutations. For the purposes of understanding the rate of molecular evolution, however,
we need to make a slightly different distinction—that between effectively neutral and
effectively selected mutations. In Chapter 24, we learned that, in a finite population of N
individuals, the process of random genetic drift will not be materially altered if the intensity
of selection, s, on an allele is of lower order than 1/N. That means that the class of
evolutionarily neutral mutations includes both those that have absolutely no effect on fitness
and those whose fitness effects are less than the reciprocal of population size, so small as to
be effectively neutral.
We would like to know how much of molecular evolution is a consequence of new, favorable
adaptive mutations sweeping through a species, the picture presented by a simplistic
Darwinian view of evolution, and how much is simply the accumulation of the random
fixation of effectively neutral mutations. Mutations that are effectively deleterious need not be
considered, because they will be kept at low frequencies in populations and will not contribute
to evolutionary change. If a newly arisen mutation is effectively neutral then, as pointed out in
Chapter 24, there is a probability of 1/(2N) that it will replace the previous allele because of
random genetic drift. If the rate of appearance of new effectively neutral mutations at a locus
per gene copy per generation is μ, then the absolute number of new mutational copies that will
appear in a population of N diploid individuals is 2Nμ. Each one of these new copies has a
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An Introduction to Genetic Analysis
probability of 1/(2N) of eventually taking over the population. Thus, the absolute rate of
replacement of old alleles by new ones at a locus per generation is their rate of appearance
multiplied by the probability that any one of them will eventually take over by drift
That is, we expect that in every generation there will be μ substitutions of a new allele for an
old one at each locus in the population, purely from genetic drift of effectively neutral
mutations.
MESSAGE
The rate of replacement in evolution resulting from the random genetic drift of
effectively neutral mutations is equal to the mutation rate to such alleles, μ.
The constant rate of neutral substitution predicts that, if the number of nucleotide differences
between two species is plotted against the time since their divergence from a common
ancestor, the result should be a straight line with a slope equal to μ. That is, evolution should
proceed according to a molecular clock that is ticking at the rate μ. Figure 26-17 shows such a
plot for the β-globin gene. The results are quite consistent with the claim that nucleotide
substitutions have been effectively neutral over the past 500 million years. Two sorts of
nucleotide substitutions are plotted: synonymous substitutions that are from one alternative
codon to another, making no change in the amino acid, and nonsynonymous substitutions
that result in an amino acid change. Figure 26-17 shows a much lower slope for
nonsynonymous substitutions than that for synonymous changes, which means that the
mutation rate to nonsynonymous substitutions is much lower than that to synonymous ones.
This is precisely what we expect. The mutation rate to neutral alleles, μ, is the product of the
intrinsic nucleotide mutation rate, M, and the proportion of all mutations that are neutral, f.
That is,
and it is reasonable that mutations that cause an amino acid substitution should more often
have a deleterious effect, s, above the threshold for neutral evolution and therefore the
proportion of neutral changes, f, will be smaller. It is important to note that these observations
do not show that synonymous substitutions have no selective constraints on them; rather they
show that these constraints are, on the average, not as strong as for amino acids. In fact,
synonymous changes do have effects on probabilities of correct splicing, on the stability and
lifetime of mRNA, on use by the translation apparatus of the available pool of tRNA
molecules, and thus on the rate of translation and the folding of the translated polypeptide.
Another prediction of neutral evolution is that different proteins will have different clock rates,
because the metabolic function of some proteins will be much more sensitive to changes in
their amino acid sequence. Proteins in which every amino acid makes a difference will have
smaller values of the effectively neutral mutation rate, Mf, than will proteins that are more
tolerant of substitution. Figure 26-18 shows a comparison of the clocks for fibrinopeptides,
hemoglobin, and cytochrome c. That fibrinopeptides have a much higher proportion of neutral
mutations is reasonable because these peptides are merely a nonmetabolic safety catch, cut
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An Introduction to Genetic Analysis
out of fibrinogen to activate the blood-clotting reaction. From a priori considerations, why
hemoglobins are less sensitive to amino acid changes than is cytochrome c is less obvious.
MESSAGE
The rate of neutral evolution for the amino acid sequence of a protein depends on the
sensitivity of a protein's function to amino acid changes.
The demonstration of the molecular clock argues that most nucleotide substitutions are neutral,
but it does not tell us how much of molecular evolution is adaptive. One way of detecting
adaptive evolution of a protein is by comparing the synonymous and nonsynonymous
polymorphisms within species with the synonymous and nonsynonymous changes between
species. Under the operation of evolution by random genetic drift, polymorphism within a
species is simply a stage in the eventual fixation of a new allele; so the ratio of
nonsynonymous to synonymous polymorphisms within a species should be the same as the
ratio of nonsynonymous to synonymous substitutions between species. On the other hand, if
the amino acid changes between species have been driven by a positive adaptive selection,
there ought to be an excess of nonsynonymous changes between species. Table 26-6 shows an
application of this principle by J. MacDonald and M. Kreitman to the alcohol dehydrogenase
gene in three closely related species of Drosophila. Clearly, there is an excess of amino acid
replacements between species over what is expected from the polymorphisms.
Summary
The Darwinian theory of evolution is a variational scheme that explains the changes that
occur in populations of organisms as being the result of changes in the relative frequencies of
different variants in the population. The processes that give rise to the variation within the
population are causally independent of the processes that are responsible for the differential
reproduction of the various types. It is this independence that is meant when it is said that
mutations are “random.” The process of mutation supplies undirected variation, whereas the
process of natural selection culls this variation, increasing the frequency of those variants that
by chance are better able to survive and reproduce. Many are called, but few are chosen. Thus,
if there is no variation within a species for some trait, there can be no evolution. Moreover,
that variation must be influenced by genetic differences. If differences are not heritable, they
cannot evolve, because the differential reproduction of the different variants will not carry
across generational lines. Thus, all hypothetical evolutionary reconstructions depend critically
on whether the traits in question are, in fact, heritable.
The evolutionary divergence of populations in space and time is not only a consequence of
natural selection. Natural selection is not a globally optimizing process that finds the “best”
organisms for a particular environment. Instead, it finds one of a set of alternative “good”
solutions to adaptive problems, and the particular outcome of selective evolution in a
particular case is subject to chance historical events. Random factors such as genetic drift and
the chance occurrence or loss of new mutations may result in radically different outcomes of
an evolutionary process even when the force of natural selection is the same. The metaphor
usually employed is that there is an “adaptive landscape” of genetic combinations and that
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An Introduction to Genetic Analysis
natural selection leads the population to a “peak” in that landscape, but only to one of several
alternative local peaks.
The vast diversity of different living forms that have existed is a consequence of independent
evolutionary histories that have occurred in separate populations. For different populations to
diverge from each other, they must not exchange genes; so the independent evolution of large
numbers of different species requires that these species be reproductively isolated from each
other. Indeed, we define a species as a population of organisms that exchange genes within it
but is reproductively isolated from other populations. The mechanisms of reproductive
isolation may be prezygotic or postzygotic. Prezygotic isolating mechanisms are those that
prevent the union of gametes of two species. These mechanisms may be behavioral
incompatability of the males and females of the different species, differences in timing or
place of their sexual activity, anatomical differences that make mating mechanically
impossible, or physiological incompatability of the gametes themselves. Postzygotic isolating
mechanisms include the inability of hybrid embryos to develop to adulthood, sterility of
hybrid adults, and the breakdown of later generations of recombinant genotypes. For the most
part, the genetic differences responsible for the isolation between closely related species are
spread over all the chromosomes, although in species with chromosomal sex determination
there may be a concentration of incompatability genes on the sex chromosome.
If new functions are to arise in evolution without the sacrifice of previously existing functions,
new DNA must be made available for the evolution of added genes. This new DNA may arise
by duplication of the entire genome, polyploidy, followed by a slow evolutionary divergence
of the extra chromosomal set. This has been a frequent occurrence in plants. An alternative is
the duplication of single genes followed by selection for differentiation. Yet another source of
DNA, recently discovered, is the entry into the genome of DNA from totally unrelated
organisms by infection followed by integration of the foreign DNA into the nuclear genome
or by the formation of extranuclear cell organelles with their own genomes. Mitochondria and
chloroplasts in higher organisms have arisen by this route.
Not all of evolution is impelled by natural selective forces. If the selective difference between
two genetic variants is small enough, less than the reciprocal of population size, there may be
a replacement of one allele by another purely by genetic drift. A great deal of molecular
evolution seems to be the replacement of one protein sequence by another one of equivalent
function. The evidence for this neutral evolution is that the number of amino acid differences
between two different species in some molecule—for example, hemoglobin—is directly
proportional to the number of generations since their divergence from a common ancestor in
the evolutionary past. Such a “molecular clock” with a constant rate of change would not be
expected if the selection of differences were dependent on particular changes in the
environment. Moreover, we expect the clock to run faster for proteins such as fibrinopeptides,
in which the amino acid composition is not critical for the function, and this difference in
clock rate is, in fact, observed. Thus we cannot assume without evidence that evolutionary
changes are the result of adaptive natural selection.
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An Introduction to Genetic Analysis
Overall, genetic evolution is a historical process that is subject to historical contingency and
chance, but it is constrained by the necessity of organisms to survive and reproduce in a
constantly changing world.
Solved Problems
1. Two closely related species are found to be fixed for two different electrophoretically
detected alleles at a locus encoding an enzyme. How could you demonstrate that this
divergence is a result of natural selection rather than neutral evolution?
Solution
a. Obtain DNA sequences of the gene from a number of separate individuals or strains from
each of the two species. Ten or more sequences from each species would be desirable.
b. Tabulate the nucleotide differences among individuals within each species
(polymorphisms), and classify these differences as either those that result in amino acid
changes (replacement polymorphisms) or those that do not change the amino acid
(synonymous polymorphisms).
c. Make the same tabulation of replacement and synonymous changes for the differences
between the species, counting only those differences that completely differentiate the species.
That is, do not count a polymorphism in one species that includes a variant that is seen in the
other species.
d. If the ratio of replacement differences between the species to synonymous differences
between the species is greater than the ratio of replacement polymorphisms to synonymous
polymorphisms, then select for amino acid change.
e. Test the statistical significance of the observed greater ratio by a 2 × 2 chi-square test of
the following table:
2. How could the molecular evolution of a set of different proteins be used to provide
evidence of the relative importance of exact amino acid sequence to the function of each
protein?
See answer
Solution
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An Introduction to Genetic Analysis
Obtain DNA sequences from the genes for each protein from a wide variety of very divergent
species whose approximate time to a common ancestor is known from the fossil record.
Translate the DNA sequences into amino acid sequences. For each protein, plot the observed
amino acid difference for each pair of species against the estimated time of divergence for
those species. The line for each protein will have a slope that is proportional to the amount of
functional constraint on amino acid substitution in that protein. Highly constrained proteins
will have very low rates of substitution, whereas more tolerant proteins will have higher
slopes.
Problems
1. What is the difference between a transformational and a variational scheme of evolution?
Give an example of each (not including the Darwinian theory of organic evolution).
2. What are the three principles of Darwin's theory of variational evolution?See answer
3. Why is the Mendelian explanation of inheritance essential to Darwin's variational
mechanism for evolution? What would the consequences for evolution be if inheritance
were by the mixing of blood? What would the consequence for evolution be if
heterozygotes did not segregate exactly 50 percent of each of the two alleles at a locus but
were consistently biased toward one or the other allele?
4. If the mutation rate to a new allele is 10−5, how large must isolated populations be to
prevent chance differentiation among them to develop in the frequency of this allele?See
answer
5. Suppose that a number of local populations of a species are each about 10,000 individuals
in size and that there is no migration between them. Suppose, further, that they were
originally established from a large population with the frequency of an allele A at some
locus equal to 0.4. Show by approximate sketches what the distribution of allele
frequencies among the local populations would be after 100, 1000, 5000, 10,000, and
100,000 generations of isolation.
6. Show the results for the populations described in Problem 5 if there were an exchange of
migrants among the populations at the rate of (a) one migrant individual per population
every 10 generations; (b) one migrant individual per population every generation.
7. Suppose that a population is segregating for two alleles at each of two loci and that the
relative probabilities of survival to sexual maturity of zygotes of the nine genotypes are as
follows:
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An Introduction to Genetic Analysis
Calculate the mean fitness, W, of the population if the allele frequencies are p(A) = 0.8
and p(B) = 0.9. What direction of change do you expect in allele frequencies in the next
generation? Make the same calculation and prediction for the allele frequencies p(A) =
0.2 and p(B) = 0.2. From inspection of the genotypic fitnesses, how many adaptive
peaks are there? What are the allele frequencies at the peak(s)?See answer
8. Suppose the genotypic fitnesses in Problem 7 were:
Calculate the mean fitness, W, for allelic frequencies p(A) = 0.5 and p(B) = 0.5.
What direction of change do you expect for the allele frequencies in the next generation?
Repeat the calculation and prediction for p(A) = 0.1 and p(B) = 0.1. From inspection
of the genotype fitnesses, how many adaptive peaks are there and where are they located?
9. What is the evidence that polyploid formation has been important in plant evolution?
10. What is the evidence that gene duplication has been the source of the α and β gene
families in human hemoglobin?See answer
11. The human blood group allele IB has a frequency of about 0.10 in European and Asian
populations but is almost entirely absent in Native American populations. What
explanations can account for this difference?
12. What is a geographical race? What is the difference between a geographical race and a
separate species? Under what conditions will geographical races of a species become new
species?See answer
13. Drosophila pseudoobscura and D. persimilis are now considered separate species, but
originally they were classified as Race A and Race B of a single species. They are
morphologically indistinguishable from each other, except for a small difference in the
genitalia of the males. When crossed in the laboratory, abundant adult F1 progeny of both
sexes are produced. Outline what program of observations and experiments you would
undertake to test the claim that the two forms are different species.
14. Using the data on amino acid similarity of the α-, β-, γ-, ζ-, and ε-globin chains given in
勇者并非无所畏惧, 而是判断出有比恐惧更重要的东西.
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An Introduction to Genetic Analysis
Table 26-4, draw a branching tree of the evolution of these chains from an original
ancestral sequence in which the order of branching in time is as consistent as possible with
the observed amino acid similarity on the assumption of a molecular clock.
15. DNA-sequencing studies for a gene in two closely related species produce the following
numbers of sites that vary:
Does this result support a neutral evolution of the gene? Does it support an adaptive
replacement of amino acids? What explanation would you offer for the observations?
Chapter 26*
2. The three principals are: (1) organisms within a species vary from one another, (2) the
variation is heritable, and (3) different types leave different numbers of offspring in future
generations.
4. A population will not differentiate from other populations by local inbreeding if:
7. The mean fitness of population 1 [p(A) = 0.8, p(B) = 0.9] is 0.92. The mean fitness of
population 2 [p(A) = 0.2, p(B) = 0.2] is 0.73. Because selection acts to increase the mean
fitness, the frequencies of both A and B should increase in the next generation. There is a
single adaptive peak at A/A · B/B. By inspection, the fitness is lowest at a/a · b/b and
highest at A/A · B/B. The allelic frequency at the peak is 1.0 for both A and B.
10. The α and β gene families show remarkable amino acid sequence similarities (see Table
26-4 of the text). Within each gene family, sequence similarities are greater and, in some
cases, member genes have identical intron-exon structure.
12. A geographical race is a population that is genetically distinguishable from other local
populations but is capable of exchanging genes with those other local populations.
A species is a group of organisms that exchange genes within the group but cannot do so
with other groups.
Populations that are geographically separated will diverge from each other as a
consequence of a combination of unique mutations, selection, and genetic drift. For
populations to di-verge enough to become reproductively isolated, spatial separation
勇者并非无所畏惧, 而是判断出有比恐惧更重要的东西.
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An Introduction to Genetic Analysis
sufficient to prevent any effective migration is usually necessary.
14.
勇者并非无所畏惧, 而是判断出有比恐惧更重要的东西.
25