Evolution__3rd_Edition

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The nearly neutral theory can
explain the observations on ...
. . . genetic variation ...
. . . unclocklike evolutionary
rates ...
. . . generation time effects ...
CHAPTER 7 / Natural Selection and Random Drift 173
We can now distinguish two random drift theories of molecular evolution. According
to Kimura’s original neutral theory, most molecular evolution occurs as one purely
neutral mutation (s = 0) is substituted for another. For the rest of this chapter I shall call
this the purely neutral theory or Kimura’s neutral theory. It should be distinguished from
the nearly neutral theory, according to which most molecular evolution occurs as one
nearly neutral mutation (4Ns < 1) is substituted for another.
7.5.3 The nearly neutral theory can explain the observed facts better
than the purely neutral theory
How can the nearly neutral theory explain the observations that did not fit the purely
neutral theory? We can start with the observation that genetic variation is much the
same within species with large population sizes as in species with small population
sizes. For purely neutral mutations, species with larger population sizes should have
more genetic variation; but they do not in fact. However, now suppose that many
mutations are nearly, rather than exactly, neutral. Moreover, suppose that most of
these nearly neutral mutations are slightly disadvantageous rather than slightly advantageous.
(The assumption is probably correct, because random mutations in a well
adapted molecule are more likely to make it worse than better.)
In a species with large populations, natural selection is more powerful than drift.
The slightly disadvantageous mutations will be eliminated and not contribute to the
observed genetic variation in that species. In species with small populations, natural
selection is weak relative to random drift. Slightly disadvantageous mutations will
behave as effectively neutral mutations. Some of them may drift up in frequency,
contributing to the observed genetic variation. Genetic variation will be lower than the
purely neutral theory predicts when population size is large. This is what is observed in
reality (Figure 7.5).
Now we turn to the molecular clock. The easier problem to deal with is the relative
inconstancy of the clock: the rate of molecular evolution is not as constant as the purely
neutral theory predicts. However, if there is a large class of nearly neutral mutations,
the rate of evolution will fluctuate over time when population sizes go up and down. As
population size decreases, more slightly disadvantageous mutations will become effectively
neutral. They may be fixed by drift, and the rate of evolution will increase. When
population size increases, the slightly disadvantageous mutations will be eliminated by
selection and the rate of evolution will slow down. The nearly neutral theory therefore
predicts a more erratic rate of evolution than the purely neutral theory.
The second problem we saw was that the molecular clock is more influenced by
generation time for synonymous than for non-synonymous changes. Ohta’s key
argument here is the relation between population size and generation length. Species
with long generation times tend to have smaller population sizes than species with
short generation times (this relation was shown empirically by Chao & Carr (1993)).
Whales, for example, live in smaller populations than fruitflies (even if we ignore the
effects of humans on the two life forms).
Mutations at synonymous sites are probably mainly neutral. In Ohta’s account,
the rate of evolution at synonymous sites is influenced by generation length simply