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Journal of Virology, May 2008, p. 4938-4945, Vol. 82, No. 10
0022-538X/08/$08.00+0     doi:10.1128/JVI.02415-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Natural Selection for Nucleotide Usage at Synonymous and Nonsynonymous Sites in Influenza A Virus Genes{triangledown}

Sergey Kryazhimskiy,1,2* Georgii A. Bazykin,3,4 and Jonathan Dushoff3,5

Program in Applied and Computational Mathematics, Princeton University, Princeton, New Jersey,1 Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania,2 Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey,3 Institute for Information Transmission Problems, Russian Academy of Sciences (Kharkevich Institute), Moscow, Russia,4 Department of Biology, McMaster University, Hamilton, Ontario, Canada5

Received 8 November 2007/ Accepted 26 February 2008

Influenza A virus is one of the best-studied viruses and a model organism for the study of molecular evolution; in particular, much research has focused on detecting natural selection on influenza virus proteins. Here, we study the dynamics of the synonymous and nonsynonymous nucleotide composition of influenza A virus genes. In several genes, the nucleotide frequencies at synonymous positions drift away from the equilibria predicted from the synonymous substitution matrices. We investigate possible reasons for this unexpected behavior by fitting several regression models. Relaxation toward a mutation-selection equilibrium following a host jump fails to explain the dynamics of the synonymous nucleotide composition, even if we allow for slow temporal changes in the substitution matrix. Instead, we find that deep internal branches of the phylogeny show distinct patterns of nucleotide substitution and that these branches strongly influence the dynamics of nucleotide composition, suggesting that the observed trends are at least in part a result of natural selection acting on synonymous sites. Moreover, we find that the dynamics of the nucleotide composition at synonymous and nonsynonymous sites are highly correlated, providing evidence that even nonsynonymous sites can be influenced by selection pressure for nucleotide composition.

* Corresponding author. Mailing address: 204K Carolyn Lynch Laboratory, University of Pennsylvania, 434 S. University Ave., Philadelphia, PA 19104. Phone: (215) 746-2188. Fax: (215) 898-8780. E-mail: skr{at}sas.upenn.edu

{triangledown} Published ahead of print on 5 March 2008.

Journal of Virology, May 2008, p. 4938-4945, Vol. 82, No. 10
0022-538X/08/$08.00+0     doi:10.1128/JVI.02415-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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