Modelos de mutação-seleção de evolução de sequência codificante com características de aptidão de sítio heterogêneo de aminoácido

terça-feira, fevereiro 23, 2010

Mutation-selection models of coding sequence evolution with site-heterogeneous amino acid fitness profiles

Nicolas Rodrigue a,1, Hervé Philippe b, and Nicolas Lartillot b

-Author Affiliations

aDepartment of Biology, University of Ottawa, Ottawa, Ontario, K1N 6N5 Canada; and

bDepartment of Biochemistry, Centre Robert Cedergren, Université de Montréal, Montréal, Québec, H3C 3J7 Canada

Edited by David M. Hillis, University of Texas at Austin, Austin, TX, and approved January 27, 2010 (received for review September 24, 2009)


Modeling the interplay between mutation and selection at the molecular level is key to evolutionary studies. To this end, codon-based evolutionary models have been proposed as pertinent means of studying long-range evolutionary patterns and are widely used. However, these approaches have not yet consolidated results from amino acid level phylogenetic studies showing that selection acting on proteins displays strong site-specific effects, which translate into heterogeneous amino acid propensities across the columns of alignments; related codon-level studies have instead focused on either modeling a single selective context for all codon columns, or a separate selective context for each codon column, with the former strategy deemed too simplistic and the latter deemed overparameterized. Here, we integrate recent developments in nonparametric statistical approaches to propose a probabilistic model that accounts for the heterogeneity of amino acid fitness profiles across the coding positions of a gene. We apply the model to a dozen real protein-coding gene alignments and find it to produce biologically plausible inferences, for instance, as pertaining to site-specific amino acid constraints, as well as distributions of scaled selection coefficients. In their account of mutational features as well as the heterogeneous regimes of selection at the amino acid level, the modeling approaches studied here can form a backdrop for several extensions, accounting for other selective features, for variable population size, or for subtleties of mutational features, all with parameterizations couched within population-genetic theory.

codon substitution     Dirichlet process    phylogeny   selection coefficients


1To whom correspondence should be addressed.

Author contributions: N.R., H.P., and N.L. designed research; N.R. performed research; N.R. analyzed data; and N.R. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

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