Site level factors that affect the rate of adaptive evolution in humans and chimpanzees; the effect of contracting population size

Abstract

AbstractIt has previously been shown in other species that the rate of adaptive evolution is higher at sites that are more exposed in a protein structure and lower between amino acid pairs that are more dissimilar. We have investigated whether these patterns are found in the divergence between humans and chimpanzees using an extension of the MacDonald-Kreitman test. We confirm previous findings and find that the rate of adaptive evolution, relative to the rate of mutation, is higher for more exposed amino acids, lower for amino acid pairs that are more dissimilar in terms of their polarity, volume and lower for amino acid pairs that are subject to stronger purifying selection, as measured by the ratio of the numbers of non-synonymous to synonymous polymorphisms (pN /pS). However, the slope of this latter relationship is significantly shallower than in Drosophila species. We suggest that this is due to the population contraction that has occurred since humans and chimpanzees diverged. We demonstrate theoretically that population size reduction can generate an artefactual positive correlation between the rate of adaptive evolution and any factor that is correlated to the mean strength of selection acting against deleterious mutations, even if there has been no adaptive evolution (the converse is also expected). Our measure of selective constraint, pN /pS, is negatively correlated to the mean strength of selection, and hence we would expect the correlation between the rate of adaptive evolution to also be negatively correlated to pN /pS, if there is no adaptive evolution. The fact that our rate of adaptive evolution is positively correlated to pN /pS suggests that the correlation does genuinely exist, but that is has been attenuated by population size contraction.