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Bioinformatics Advance Access published online on April 28, 2008
Bioinformatics, doi:10.1093/bioinformatics/btn205
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© The Author (2008). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Positive selection drives a correlation between nonsynonymous/ synonymous divergence and functional divergence

Jacob A. Tennessen 1,*

1Department of Zoology, 3029 Cordley Hall, Oregon State University, Corvallis, OR, 97331

*To whom correspondence should be addressed. Jacob A. Tennessen, E-mail: tennessj{at}science.oregonstate.edu


  Abstract

Motivation: Functional divergence among proteins is often assumed to be strongly influenced by natural selection, as inferred from the ratio of nonsynonymous 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.

Contact: tennessj{at}science.oregonstate.edu

Supplementary information: Supplementary data, including GenBank Accession numbers, are available at Bioinformatics Online

Associate Editor: Prof. Dmitrij Frishman

Received on March 6, 2008; revised on April 21, 2008; accepted on April 22, 2008

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