Evolution__3rd_Edition

170 PART 2 / Evolutionary Genetics
. . . but perhaps not in nonsynonymous
evolution
The exact form of molecular
evolution does not neatly fit the
original neutral theory ...
. . . in at least four respects
The DNA evidence for non-synonymous sites is more ambiguous. Some studies
have borne out Wilson et al.’s finding, that the generation time effect is either absent
or reduced in synonymous sites. Other studies have found that generation time
influences the rate of evolution in non-synonymous sites much as in synonymous sites.
Generation time may influence the rate of non-synonymous evolution in some genes,
or some lineages, but not others.
The factual picture that has emerged is that DNA evolution is influenced by generation
times for synonymous sites. For non-synonymous sites, where a substitution alters
the amino acid, the generation time effect is less clear. Synonymous evolution fits the
neutral theory. Non-synonymous evolution either does not fit the neutral theory, or
does not fit it so well as synonymous evolution.
7.5 The nearly neutral theory
7.5.1 The “purely” neutral theory faces several empirical problems
The different effects of generation time in the molecular clocks for synonymous and
non-synonymous evolution is one of several factual difficulties that had emerged in the
neutral theory by the late 1980s. A related problem is that the molecular clock is not
constant enough to fit the neutral theory. Molecular evolution does appear to be relatively
constant. The exact degree of constancy in the rate of evolution is difficult to
measure, for various statistical reasons, but by the time Gillespie (1991) wrote, many
authors were claiming that the rate of molecular evolution is more erratic, or more
episodic, than the neutral theory predicts. The molecular clock is not quite clock-like
enough. One explanation might be the generation time effect that we have just looked
at. If generation times fluctuate over evolutionary time, so will the rate of neutral evolution.
Alternatively, some authors doubt whether generation times influence rates of
evolution, and for them some other explanation is needed for inconstancies in the
molecular clock.
A further problem emerged in the amounts of genetic variation. The neutral theory
predicts a certain level of genetic variation, which can be expressed as heterozygosity.
The heterozygosity is predicted to increase with population size (Figure 6.6, p. 151).
Fruitflies, with large N, should have more genetic variation than horses, with small
N. In fact it turned out that levels of heterozygosity are rather constant in all species,
independent of N (Figure 7.5).
In all, the neutral theory put forward by Kimura (1968, 1983) seemed to have problems
with several points:
1. The stronger influence of generation times on the rate of synonymous evolution
than the rate of non-synonymous evolution.
2. The molecular clock, which is not constant enough.
3. Levels of heterozygosity, which are too constant between species and too low in
species with large population sizes.
4. Observed levels of genetic variation and of evolutionary rates, which are not related
in the predicted way.
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