Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 16, Pages 6263-6268Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0508279103
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Most methods for detecting Darwinian natural selection at the molecular level rely on estimating the rates or numbers of non-synonymous and synonymous changes in an alignment of protein-coding DNA sequences. In some of these methods, the nonsynonymous rate of substitution is allowed to vary across the sequence, permitting the identification of single amino acid positions that are under positive natural selection. However, it is unclear which probability distribution should be used to describe how the nonsynonymous rate of substitution varies across the sequence. One widely used solution is to model variation in the nonsynonymous rate across the sequence as a mixture of several discrete or continuous probability distributions. Unfortunately, there is little population genetics theory to inform us of the appropriate probability distribution for among-site variation in the nonsynonymous rate of substitution. Here, we describe an approach to modeling variation in the nonsynonymous rate of substitution by using a Dirichlet process mixture model. The Dirichlet process allows there to be a countably infinite number of nonsynonymous rate classes and is very flexible in accommodating different potential distributions for the nonsynonymous rate of substitution. We implemented the model in a fully Bayesian approach, with all parameters of the model considered as random variables.
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