Evolution__3rd_Edition

190 PART 2 / Evolutionary Genetics
7.9 Conclusion: 35 years of research on molecular
evolution
In 1968, Kimura proposed the neutral theory of molecular evolution. His original
argument was mainly based, in theory, on genetic loads and, in fact, on amino acid
evolution. Neither his particular claim a that most molecular evolution proceeds by
the random drift of neutral mutations a nor his argument using genetic loads, nor his
evidence for proteins, has survived in its original form. However, he stimulated a
huge area of research, which arguably led to a paradigm shift in our understanding of
molecular evolution.
Kimura’s neutral theory has developed into the nearly neutral theory. The nearly
neutral theory shares with its predecessor the claim that most molecular evolution is by
random drift a but the drift of nearly neutral (4Ns < 1 or Ns < 1) rather than exactly
neutral (s = 0) mutations. Since Kimura first wrote, biologists have come to realize that
DNA contains huge regions of non-coding sequences. If we use use the nearly neutral
rather than the original, purely neutral theory, and confine it to substitutions in noncoding
DNA and synonymous substitutions in coding DNA, then many (perhaps
most) biologists accept a neutralist interpretation of molecular evolution. Most evolution
at the DNA level is by random drift.
However, non-coding DNA is in some respects biologically less interesting than
coding DNA. Non-synonymous substitutions, which alter amino acids, are biologically
more important in the sense that they influence the form and functioning of the body.
If we concentrate on non-synonymous evolution, in coding regions, then it is probably
not true that most biologists are neutralists. We do not know the relative importance of
drift and selection in driving amino acid change. Indeed, for most of the past 35 years
we have lacked a decisive method to find out the relative importance of drift and selection.
Molecular evolution is now entering the genomics era. Genomic data hold out the
promise both of revealing the localities within the DNA where natural selection acts,
and also of estimating the fractions of evolutionary substitutions that have been driven
by natural selection and by random drift.
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