Positive selection drives a correlation between non-synonymous/ synonymous divergence and functional divergence

Abstract

Motivation: Functional divergence among proteins is often assumed to be strongly influenced by natural selection, as inferred from the ratio of non-synonymous nucleotide divergence (dN) to synonymous nucleotide divergence (dS). That is, the more a mutation changes protein function, the more likely it is to be either selected against or selectively favored, and because the dN/ dS ratio is a measure of natural selection, this ratio can be used to predict the degree of functional divergence (dF). However, these hypotheses have rarely been experimentally tested. Results: I present a novel method to address this issue, and demonstrate that divergence in bacteria-killing activity among animal antimicrobial peptides is positively correlated with the log of the dN/ dS ratio. The primary cause of this pattern appears to be that positively selected substitutions change protein function more than neutral substitutions do. Thus, the dN/dS ratio is an accurate estimator of adaptive functional divergence. © The Author 2008. Published by Oxford University Press. All rights reserved.