Evolution__3rd_Edition

182 PART 2 / Evolutionary Genetics
The two explanations can be tested
between
dN/dS ratios provide evidence of
selection in some examples
Wyckoff et al. thought of several ways round this dilemma. For instance, they looked
for dN/dS ratios of more than one. Relaxed selection alone cannot take the ratio above
one. When selection ceases to act on a DNA sequence, both non-synonymous and
synonymous changes will be equally neutral and occur at the same rate. The dN/dS
ratio will equal one. By contrast, positive selection in favor of change can take the
dN/dS ratio much higher. If dN/dS 1, it is a strong sign that natural selection has
been driving change.
In summary, we have three zones of dN/dS ratio, and three associated evolutionary
interpretations.
1. dN/dS low, perhaps 0.1–0.2 (though the actual value can vary down the DNA).
Interpretation: synonymous change is neutral; there is no evidence that selection is
driving the change in amino acids.
2. dN/dS between 0.2 and 1. Interpretation: either selection has been acting to change
the amino acid sequence or selection has been relaxed; we do not know which.
3. dN/dS higher than 1. Interpretation: natural selection has been acting to change the
amino acid sequence.
Biologists have mainly been interested in using dN/dS ratios as evidence for positive
selection. For them, relaxed selection is something to be ruled out. In the protamine
gene, dN/dS > 1 and we have evidence of adaptive evolutionary change rather than
relaxed selection. (Wyckoff et al. also presented other evidence for positive selection in
protamine evolution, including evidence from the McDonald–Kreitman test that we
discuss in the next section.)
High dN/dS ratios have been found in several genes. The genes concerned look like
the sort of genes that may undergo rapid adaptive evolutionary change. The first genes
to be found with high dN/dS were the HLA genes. HLA genes recognize parasite
invaders in the body. They probably evolve fast to keep up with evolutionary changes in
the parasites, which evolve to outsmart their host’s immune systems. Other genes with
high dN/dS are in signal–receptor systems and in the reproductive system. 2
The relation between the two arguments in this section, and in the previous section,
may be worth clarifying. It might seem that low dN/dS ratios were used as evidence of
selection in the previous section and now high dN/dS ratios are being used as evidence
of selection here. The answer is that the two sections are concerned with testing for different
kinds of selection. Kreitman (1983) found synonymous, but no non-synonymous,
variation between copies of one alcohol dehydrogenase allele in fruitflies. This shows
that natural selection has been acting to prevent change. Wyckoff et al. (2000) found
more non-synonymous than synonymous evolution in the protamine genes of apes.
This shows, or at least suggests, that natural selection has driven adaptive evolutionary
change. Kreitman’s evidence by itself fits with all evolutionary change being by drift
(there is evidence for selective changes in the Adh gene, but it comes from other
research). Wyckoff et al.’s evidence challenges, and possibly refutes, random drift as the
explanation of evolution in the protamine genes of humans and other apes.
Box 7.4 looks at a practical application of dN/dS ratios, in the genes coding for leptin.
2 The possible rapid evolution of at least some reproductive systems’ genes is a recurrent subtheme in this
book. We return to it in Sections 12.4.7 (p. 336), 13.3.2 (p. 357), and 14.12 (p. 417). Swanson & Vacquier
(2002) is a recent empirical review.
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