Document Detail

Identifying sites under positive selection with uncertain parameter estimates.
MedLine Citation:
PMID:  16936785     Owner:  NLM     Status:  MEDLINE    
Codon-based substitution models are routinely used to measure selective pressures acting on protein-coding genes. To this effect, the nonsynonymous to synonymous rate ratio (dN/dS = omega) is estimated. The proportion of amino-acid sites potentially under positive selection, as indicated by omega > 1, is inferred by fitting a probability distribution where some sites are permitted to have omega > 1. These sites are then inferred by means of an empirical Bayes or by a Bayes empirical Bayes approach that, respectively, ignores or accounts for sampling errors in maximum-likelihood estimates of the distribution used to infer the proportion of sites with omega > 1. Here, we extend a previous full-Bayes approach to include models with high power and low false-positive rates when inferring sites under positive selection. We propose some heuristics to alleviate the computational burden, and show that (i) full Bayes can be superior to empirical Bayes when analyzing a small data set or small simulated data, (ii) full Bayes has only a small advantage over Bayes empirical Bayes with our small test data, and (iii) Bayesian methods appear relatively insensitive to mild misspecifications of the random process generating adaptive evolution in our simulations, but in practice can prove extremely sensitive to model specification. We suggest that the codon model used to detect amino acids under selection should be carefully selected, for instance using Akaike information criterion (AIC).
Stéphane Aris-Brosou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genome / National Research Council Canada = Génome / Conseil national de recherches Canada     Volume:  49     ISSN:  0831-2796     ISO Abbreviation:  Genome     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-08-28     Completed Date:  2007-02-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8704544     Medline TA:  Genome     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  767-76     Citation Subset:  IM    
Department of Biology, University of Ottawa, Ottawa, ON, Canada.
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MeSH Terms
Amino Acids / genetics*
Bayes Theorem
Genes, env
HIV-1 / genetics
Markov Chains
Models, Genetic*
Monte Carlo Method
Selection, Genetic*
Reg. No./Substance:
0/Amino Acids; 0/Codon

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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