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MBE Advance Access originally published online on March 10, 2004
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Mol. Biol. Evol. 21(7):1201-1213. 2004
DOI: 10.1093/molbev/msh088
© 2004 by the Society for Molecular Biology and Evolution. ISSN: 0737-4038


Research Article

Estimating Absolute Rates of Synonymous and Nonsynonymous Nucleotide Substitution in Order to Characterize Natural Selection and Date Species Divergences

Tae-Kun Seo{dagger}, Hirohisa Kishino{ddagger} and Jeffrey L. Thorne{dagger}

{dagger} Bioinformatics Research Center, Box 7566, North Carolina State University
{ddagger} Laboratory of Biometrics, Graduate School of Agriculture and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan

E-mail: seo{at}statgen.ncsu.edu

Abstract

The rate of molecular evolution can vary among lineages. Sources of this variation have differential effects on synonymous and nonsynonymous substitution rates. Changes in effective population size or patterns of natural selection will mainly alter nonsynonymous substitution rates. Changes in generation length or mutation rates are likely to have an impact on both synonymous and nonsynonymous substitution rates. By comparing changes in synonymous and nonsynonymous rates, the relative contributions of the driving forces of evolution can be better characterized. Here, we introduce a procedure for estimating the chronological rates of synonymous and nonsynonymous substitutions on the branches of an evolutionary tree. Because the widely used ratio of nonsynonymous and synonymous rates is not designed to detect simultaneous increases or simultaneous decreases in synonymous and nonsynonymous rates, the estimation of these rates rather than their ratio can improve characterization of the evolutionary process. With our Bayesian approach, we analyze cytochrome oxidase subunit I evolution in primates and infer that nonsynonymous rates have a greater tendency to change over time than do synonymous rates. Our analysis of these data also suggests that rates have been positively correlated.

Key Words: Bayesian method • Markov chain Monte Carlo (MCMC) • rate change model • lognormal • evolutionary rate • selection • synonymous rate • nonsynonymous rate


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