Evolution__3rd_Edition

..
The genomic era is allowing new
tests of selection and drift, ...
. . . and identifying sites where
selection appears to have operated
CHAPTER 7 / Natural Selection and Random Drift 189
the neutral theory. Natural selection is a negative force, preventing certain changes.
Evolutionary changes, when they do occur, are probably by neutral drift. However, the
evidence for selective constraints means that evolution at synonymous sites is probably
not “pan-neutral.” Not all synonymous mutations are neutral. The rate of synonymous
evolution will then be somewhat below the total mutation rate.
The argument we have looked at in this section is widely accepted for single-celled
life forms. But the picture for multicellular life forms such as fruitflies and mammals
may differ. The mutation-bias hypothesis may be more viable for mammals than for
bacteria and yeast.
7.8.6 Positive and negative selection leave their signatures in
DNA sequences
We have looked at five examples of the ways in which genomic sequences can be used to
study natural selection. In the cases of the alcohol dehydrogenase gene and of codon
bias, the effect of selection was negative: selection acted against disadvantageous mutations,
preventing evolutionary change. Such evolutionary changes as do take place
among synonymous codons are probably mainly driven by drift, but selection is acting
to prevent some changes. The other three examples (elevated dN/dS ratios, different
dN/dS ratios within and between species, and convergent evolution in lysozymes) illustrate
positive selection: natural selecting actively favoring certain changes. The amino
acid changes in the protamine and lysozyme genes have probably been driven by selection
rather than drift.
The examples illustrate two points. One is that the genomic era has opened up
new ways to study selection. We saw earlier how natural selection can be studied
ecologically, such as in the peppered moth or in insecticide resistance (Sections 5.7–
5.8, pp. 108–18). The peppered moth has identifiable character states (light or dark
coloration) and the fitnesses of these states can be measured in natural environments.
This kind of ecological research is not the only way that selection has been studied,
but it contrasts with research in the genomic era. When we look at dN/dS ratios, for
instance, we are not looking at organismic character states, nor measuring fitnesses. We
are counting large numbers of evolutionary changes, statistically, in a mass of sequence
data. In Section 8.10 (p. 210) we shall see another statistical method for detecting selection
in sequence data, in the phenomenon of selective sweeps.
Secondly, the examples show that neutralism is not the whole story of molecular
evolution. Random drift probably explains the majority of molecular evolution a
provided we count “non-informational” changes. Evolution in non-coding regions
of the DNA, and in synonymous sites within genes, looks neutral. But in the nonsynonymous
sites of genes, where DNA changes produce amino acid changes, selection
is more important. Whole-genome analyses are being used to estimate the exact relative
importance of selection and drift in amino acid substitutions. The lysozyme example
shows how we can study the way selectin works in an identified gene. It makes sense
that selection as well as drift should matter in molecular evolution. The molecules in
living bodies are well adapted, and natural selection must work at least occasionally to
keep those adaptations up to date.