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bioRxiv · 10.1101/2020.05.13.091363

Contrast-FEL: a test for differences in selective pressures at individual sites among clades and sets of branches.

Kosakovsky Pond, S. L.·Wisotsky, S.·Escalante, A. A.·Rife Magalis, B.·Weaver, S.
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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 dN/dS 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. 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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Kosakovsky Pond, S. L., Wisotsky, S., Escalante, A. A., Rife Magalis, B., Weaver, S.. 2020-05-15. Contrast-FEL: a test for differences in selective pressures at individual sites among clades and sets of branches.. https://doi.org/10.1101/2020.05.13.091363

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