Evolution__3rd_Edition

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homozygotes by normal Mendelian segregation in the next
generation. For one locus, heterozygote advantage is plausible.
A few individuals die because they are homozygotes, but the
population continues to exist.
However, initial surveys suggested that about 3,000 loci might
be polymorphic in fruitflies. Suppose all 3,000 were maintained by
heterozygous advantage. The chance that an individual would be
heterozygous at all 3,000 is essentially zero. All individuals will be
homozygous at many hundreds of loci. If each such locus lowers
fitness by a few percent, every individual will be dead several
times over. (In terms of the example of sickle cell anemia, it is as if
everyone has some such condition at hundreds of their loci. You
might survive one of them, but not all of them.) Kimura concluded
that it was impossible for natural selection to maintain all the
genetic variation observed at the molecular level. The genetic
variation must be maintained by random drift, which explains
polymorphism by a balance of drift and mutation (Section 6.6,
p. 150). Neutral variation does not create a genetic load.
Kimura’s argument retains its interest, but is now generally
thought to be inconclusive, for two main reasons. One is that the
upper limits on the rate of evolution, and on the tolerable level of
genetic variation, can be raised if we allow for soft selection.
Haldane and Kimura’s calculation assumed hard selection. Hard
selection means that natural selection adds to the amount of
mortality, decreasing the population size. We can distinguish
between “background” mortality, due to normal ecological
processes (Section 4.1, p. 72), and “selective” mortality, due to
the action of natural selection. Organisms produce many more
offspring than can survive, and many die without reproducing.
If a cod produces 5,000,000 eggs, on average 4,999,998 die
before reproducing, because of the operation of various ecological
mortality factors. Natural selection is hard if it reduces the number
of survivors below two. Natural selection is soft if converts some
of the background ecological mortality into selective mortality.
Population size is not reduced if selection is soft.
As a concrete example, imagine the population size is limited by
the number of breeding territories. Only 100 territories exist in an
area, and non-owners soon die of starvation. The 100 territory
owners produce 10 eggs each, making 1,000 eggs in all. Half the
eggs die before growing up into adults, such that 500 adults
compete for the 100 territories each generation (400 will fail a
though the numbers might need adjusting if gender introduces
complexities). Consider first extreme soft selection. A new
advantageous genotype arises, which increases juvenile survival,
perhaps by 20%. Once the genotype is fixed, 600 juveniles will
survive to become adults. However, the same 100 territories exist
and the reproductive output of the population will not be altered.
Compare that with hard selection. A new disease arises that is
only caught by territory holders. A new genotype arises, making
CHAPTER 7 / Natural Selection and Random Drift 163
the birds resistant to the disease; most of the birds initially have a
disease-susceptible genotype. Until the disease-resistant genotype
is being substituted by natural selection, the reproductive output
of the birds will decrease. The mortality caused by the disease is
additional. It comes on top of the ecological winnowing down,
caused by the limited supply of territories.
Substitutional load ultimately limits the rate of evolution
whether selection is hard or soft, but the limit is much lower with
hard selection. Much selection in fact is probably soft, and does not
reduce the reproductive output of a population. Evolution can then
proceed at a higher rate than that calculated by Kimura and
Haldane.
The second counterargument is that natural selection can act
jointly on many loci. In the argument above about heterozgous
advantage, we assumed that each homozygous locus in an
individual reduces fitness by a few percent. Natural selection may
not work like that. An individual may be able to survive equally well
with one, two, three, or 100 homozygous loci, and only after the
number of homozygous loci goes over some threshold, such as 500,
will that individual’s fitness seriously decrease. Then, many more
heterozygous loci can be maintained in the population than if each
locus contributes its own mortality. A similar argument can be made
for the rate of evolution. A distinction is being made here between
multiplicative fitnesses, in which each locus contributes its own
independent effect on the organism’s fitness, and epistatic
fitnesses, in which the effects of different loci are not independent.
Section 8.8 (p. 206) looks at the distinction more. It also features in
the arguments about sex in Section 12.2.2 (p. 323).
A third counterargument is that genetic variation can be
maintained by frequency-dependent selection without creating a
genetic load. (The sex ratio, which maintains the X and Y
chromosomes, is an example: see Section 12.5, p. 337.) Thus,
even if Kimura’s argument rules out heterozygous advantage
as the explanation of much genetic variation, it does not rule
out all forms of natural selection.
These counterarguments have not been shown to be correct in
fact. They are hypothetical arguments, and reduce the theoretical
force of Kimura’s case. Neutral theory, for this reason, is now
usually supported by arguments other than genetic load. However,
the arguments are still worth knowing. They have been historically
influential and also still constantly crop up, in one form or another,
in many areas of evolutionary biology. Moreover, Williams (1992)
suggested that the whole problem had been swept under the rug
rather than solved, and that biologists should be paying more
attention to the problem of loads.
Further reading: Lewontin (1974), Kimura (1983), Williams (1992),
Gillespie (1998).