4.8 Article

Contrast-FEL-A Test for Differences in Selective Pressures at Individual Sites among Clades and Sets of Branches

Journal

MOLECULAR BIOLOGY AND EVOLUTION
Volume 38, Issue 3, Pages 1184-1198

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/molbev/msaa263

Keywords

evolutionary model; codon model; selective differences; mechanisms adaptation

Funding

  1. NIH/NIGMS [R01 GM093939]
  2. NIH/NIAID [AI134384]

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Researchers have developed a simple method, Contrast-FEL, for identifying specific sites within genes evolving differently in a phylogenetic tree. Through extensive simulations, they have shown that this method has high power and can effectively control false positive rates when the model is correctly specified.
A number of evolutionary hypotheses can be tested by comparing selective pressures among sets of branches in a phylogenetic tree. When the question of interest is to identify specific sites within genes that may be evolving differently, a common approach is to perform separate analyses on subsets of sequences and compare parameter estimates in a post hoc fashion. This approach is statistically suboptimal and not always applicable. Here, we develop a simple extension of a popular fixed effects likelihood method in the context of codon-based evolutionary phylogenetic maximum likelihood testing, Contrast-FEL. It is suitable for identifying individual alignment sites where any among the K >= 2 sets of branches in a phylogenetic tree have detectably different omega ratios, indicative of different selective regimes. Using extensive simulations, we show that Contrast-FEL delivers good power, exceeding 90% for sufficiently large differences, while maintaining tight control over false positive rates, when the model is correctly specified. We conclude by applying Contrast-FEL to data from five previously published studies spanning a diverse range of organisms and focusing on different evolutionary questions.

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