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

Abstract 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 s...

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Bibliographic Details
Published in:Molecular biology and evolution 2021-03, Vol.38 (3), p.1184-1198
Main Authors: Kosakovsky Pond, Sergei L, Wisotsky, Sadie R, Escalante, Ananias, Magalis, Brittany Rife, Weaver, Steven
Format: Article
Language:English
Subjects:
Codon
Evolution
Methods
Phylogeny
Simulation methods
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Summary:Abstract 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 ω 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.
ISSN:1537-1719
0737-4038
1537-1719
DOI:10.1093/molbev/msaa263