Evolution__3rd_Edition

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Elevated dN/dS ratios are observed
in some genes
They can be explained by natural
selection ...
. . . or by relaxed selection
CHAPTER 7 / Natural Selection and Random Drift 181
Figure 7.1b for synonymous mutations. Natural selection is powerfully maintaining
the amino acid sequence, while synonymous changes evolve by drift.
7.8.2 A high ratio of non-synonymous to synonymous changes
provides evidence of selection
When we compare the DNA sequence of a gene in two species, the usual result is for
there to be more synonymous than non-synonymous nucleotide differences. Table 7.6
showed that synonymous evolution proceeds about five times as fast as non-synonymous
evolution. The ratio of non-synonymous differences (dN) to synonymous differences
(dS) will be about 1 : 5 or 0.2. As we have seen, synonymous evolution is faster because
fewer synonymous mutations are disadvantageous, and more are neutral, than nonsynonymous
mutations. At least some amino acid changes are disadvantageous, and
this slows down the rate of non-synonymous evolution.
However, some exceptional genes have been found in which the ratio of nonsynonymous
to synonymous evolution (the dN/dS ratio) is elevated. For example,
Wyckoff et al. (2000) studied the protamine genes in the evolution of the great apes,
including humans. The protamines function in the male reproductive system, and the
genes evolve rapidly. Their evolution shows a high dN/dS ratio. The ratio for one
protamine gene, prm1, for instance is 13.
What is the cause of elevated dN/dS ratios, such as we see in the protamine genes?
One possibility is chance a the probability of a dN/dS ratio can be estimated statistically,
and any one case may be a random blip in the data. What if we rule out chance?
Two processes have been identified that increase the ratio of non-synonymous to
synonymous evolutionary changes. One is positive selection in favor of a change in
gene function. The other is relaxed selection.
The rate of amino acid-changing, non-synonymous evolution is usually low because
change is disadvantageous. The protein that the gene codes for is probably well, or even
perfectly, adapted and most or all non-synonymous change is for the worse. However,
natural selection could favor a change in the protein. Then the rate of non-synonymous
evolution will increase, while the rate of synonymous change will continue as normal,
by random drift. Thus an elevated dN/dS ratio can result when natural selection has
favored a change in the protein coded by a gene.
Alternatively, the dN/dS ratio can go up when natural selection is relaxed. Natural
selection normally prevents amino acid changes. If natural selection is stopped from
acting, the rate of amino acid evolution will increase. Changes that were disadvantageous
become neutral in the absence of selection. Natural selection may be relaxed in
humans, by medical care and other cultural practices that act against natural selection.
More generally, a rapid increase in population size is a sign that selection has been
relaxed. When a population colonizes some unexploited territory with abundant
resources, there may be a phase of rapid population growth. Natural selection will
probably be relaxed during this phase.
The two explanations for elevated dN/dS ratios are frustrating because they are
conceptually almost opposite. The same data may mean either that positive selection,
in favor of change, has been acting, or that negative selection, against change, has been
relaxed. The rate of non-synonymous evolution could go up either way.