Evolution, 4th Edition

gENETIC dRIfT: EvolUTIoN AT RANdoM 185

possibility is that most nonsynonymous mutations are deleterious and are removed

by purifying selection. In that case, the dN/dS ratio will be smaller than 1. These

interpretations of the dN/dS ratio are summarized as follows:

dN/dS < 1 Most nonsynonymous mutations are deleterious and

removed by purifying selection

dN/dS ≈ 1 Nonsynonymous and synonymous mutations are

evolving largely neutrally

dN/dS > 1 Many of the nonsynonymous differences between the

species were fixed by positive selection

The dN/dS ratio for the BRCA1 gene is greater than 1 along two branches of the

primate phylogeny, with the highest ratios occurring on the branches leading to

humans and chimps (see Figure 7.20). What caused the positive selection is not

certain, but there are tantalizing suggestions. The BRCA1 protein is important to

the repair of damaged DNA, which helps explain why mutations in the gene can

cause cancer. A plausible hypothesis is that BRCA1 also helps thwart infections by

interacting with viral DNA or proteins [22]. Perhaps coevolution with viruses drove

the rapid evolution of the BRCA1 gene, with the unfortunate side effect that it is

now more likely to mutate to a form that can trigger a cancer.

The dN/dS ratio for BRCA1 in the human lineage is very unusual: most genes

have ratios much smaller than 1. FIGURE 7.21 shows the distribution of dN/dS ratios

in a comparison of 15,350 genes in humans and mice. (The dN/dS ratio for BRCA1

in the human lineage is so high that it falls beyond the right end of this distribu-

tion.) This distribution suggests that most mutations at nonsynonymous sites are

deleterious and are removed by purifying selection, while beneficial mutations are

much rarer.

Futuyma Kirkpatrick Evolution, 4e

Sinauer Associates

Troutt Visual Services

Evolution4e_07.21.ai Date 11-14-2016 01-18-17 01-24-17

Number of genes

3000

2500

2000

1500

1000

500

0

0.1 0.2 0.3

dN/dS

0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.4

Purifying

selection

Positive

selection

FIGURE 7.21 The distribution of the dN/dS ratios in a comparison of 15,350 loci

between humans and mice shows the ratio is typically much smaller than 1 (vertical

dashed line). This shows that nonsynonymous mutations are typically fixed much more

rarely than synonymous mutations. This suggests that most nonsynonymous muta-

tions are deleterious and removed by purifying selection, and that most differences

between species are selectively neutral and evolved by drift. Values of dN/dS greater

than 1 are rare, and suggest positive selection has acted on the locus. (After [29].)

07_EVOL4E_CH07.indd 185 3/23/17 9:09 AM