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MBE Advance Access published online on August 17, 2005
Molecular Biology and Evolution, doi:10.1093/molbev/msi232
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© The Author 2005. 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@oupjournals.org
Accepted June 27, 2005

Research Article

Site-to-Site Variation of Synonymous Substitution Rates

Sergei Kosakovsky Pond 1 and Spencer V. Muse 2*

1 Antiviral Research Center, University of California, San Diego CA 92103
2 Bioinformatics Research Center, North Carolina State University, Raleigh NC 27695-7566

* To whom correspondence should be addressed.
Spencer V. Muse, E-mail: muse{at}stat.ncsu.edu


  Abstract

We develop a new model for studying the molecular evolution of protein-coding DNA sequences. In contrast to existing models, we incorporate the potential for site-to-site heterogeneity of both synonymous and nonsynonymous substitution rates. We demonstrate that within-gene heterogeneity of synonymous substitution rates appears to be common. Using the new family of models we investigate the utility of a variety of new statistical inference procedures, and we pay particular attention to issues surrounding the detection of sites undergoing positive selection. We discuss how failure to model synonymous rate variation in the model can lead to misidentification of sites as positively selected.

Keywords: Synonymous substitution rate; positive selection; molecular evolution; codon model; model selection.
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