A Dirichlet Process Model for Detecting Positive Selection in Protein-Coding DNA Sequences
A Dirichlet process model for detecting positive selection in protein-coding DNA sequences John P. Huelsenbeck*†, Sonia Jain‡, Simon W. D. Frost§, and Sergei L. Kosakovsky Pond§ *Section of Ecology, Behavior, and Evolution, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116; ‡Division of Biostatistics and Bioinformatics, Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, CA 92093-0717; and §Antiviral Research Center, University of California at San Diego, 150 West Washington Street, La Jolla, CA 92103 Edited by Joseph Felsenstein, University of Washington, Seattle, WA, and approved March 1, 2006 (received for review September 21, 2005) Most methods for detecting Darwinian natural selection at the natural selection that is present at only a few positions in the molecular level rely on estimating the rates or numbers of non- alignment (21). In cases where such methods have been successful, synonymous and synonymous changes in an alignment of protein- many sites are typically under strong positive selection (e.g., MHC). coding DNA sequences. In some of these methods, the nonsyn- More recently, Nielsen and Yang (2) developed a method that onymous rate of substitution is allowed to vary across the allows the rate of nonsynonymous substitution to vary across the sequence, permitting the identification of single amino acid posi- sequence. The method of Nielsen and Yang has proven useful for tions that are under positive natural selection. However, it is detecting positive natural selection in sequences where only a few unclear which probability distribution should be used to describe sites are under directional selection.
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