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MBE Advance Access originally published online on January 29, 2009
Molecular Biology and Evolution 2009 26(4):937-949; doi:10.1093/molbev/msp018
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© The Author 2009. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Articles

A History of Recurrent Positive Selection at the Toll-Like Receptor 5 in Primates

Gabriela Wlasiuk*, Soofia Khan*, William M. Switzer{dagger} and Michael W. Nachman*

* Department of Ecology and Evolutionary Biology, University of Arizona, Tuscon, AZ
{dagger} Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA

E-mail: wlasiuk{at}email.arizona.edu.

Accepted for publication January 25, 2009.

Many genes involved in immunity evolve rapidly. It remains unclear, however, to what extent pattern-recognition receptors (PRRs) of the innate immune system in vertebrates are subject to recurrent positive selection imposed by pathogens, as suggested by studies in Drosophila, or whether they are evolutionarily constrained. Here, we show that Toll-like receptor 5 (TLR5), a member of the Toll-like receptor family of innate immunity genes that responds to bacterial flagellin, has undergone a history of adaptive evolution in primates. We have identified specific residues that have changed multiple times, sometimes in parallel in primates, and are thus likely candidates for selection. Most of these changes map to the extracellular leucine-rich repeats involved in pathogen recognition, and some are likely to have an effect on protein function due to the radical nature of the amino acid substitutions that are involved. These findings suggest that vertebrate PRRs might show similar patterns of evolution to Drosophila PRRs, in spite of the acquisition of the more complex and specific vertebrate adaptive immune system. At shorter timescales, however, we found no evidence of adaptive evolution in either humans or chimpanzees. In fact, we found that one mutation that abolishes TLR5 function is present at high frequencies in many human populations. Patterns of variation indicate that this mutation is not young, and its high frequency suggests some functional redundancy for this PRR in humans.

Key Words: Toll-like receptor 5 • TLR5 • adaptive evolution • dN/dS • premature stop codon • TLR5392STOP

Edward Holmes, Associate Editor


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