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MBE Advance Access originally published online on May 29, 2008
Molecular Biology and Evolution 2008 25(9):1809-1824; doi:10.1093/molbev/msn123
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© The Author 2008. 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 Maximum Likelihood Method for Detecting Directional Evolution in Protein Sequences and Its Application to Influenza A Virus

Sergei L. Kosakovsky Pond*, Art F.Y. Poon*, Andrew J. Leigh Brown{dagger} and Simon D.W. Frost*

* Department of Pathology, University of California, San Diego
{dagger} Institute for Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland

E-mail: spond{at}ucsd.edu.

Accepted for publication May 10, 2008.

We develop a model-based phylogenetic maximum likelihood test for evidence of preferential substitution toward a given residue at individual positions of a protein alignment—directional evolution of protein sequences (DEPS). DEPS can identify both the target residue and sites evolving toward it, help detect selective sweeps and frequency-dependent selection—scenarios that confound most existing tests for selection, and achieve good power and accuracy on simulated data. We applied DEPS to alignments representing different genomic regions of influenza A virus (IAV), sampled from avian hosts (H5N1 serotype) and human hosts (H3N2 serotype), and identified multiple directionally evolving sites in 5/8 genomic segments of H5N1 and H3N2 IAV. We propose a simple descriptive classification of directionally evolving sites into 5 groups based on the temporal distribution of residue frequencies and document known functional correlates, such as immune escape or host adaptation.

Key Words: directional selection • evolution of influenza • maximum likelihood • episodic selection

Edward C. Holmes, Associate Editor


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