Robustness of Phylogenetic Inference to Model Misspecification Caused by Pairwise Epistasis

Abstract Likelihood-based phylogenetic inference posits a probabilistic model of character state change along branches of a phylogenetic tree. These models typically assume statistical independence of sites in the sequence alignment. This is a restrictive assumption that facilitates computational tr...

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Bibliographic Details
Published in:Molecular biology and evolution 2021-10, Vol.38 (10), p.4603-4615
Main Authors: Magee, Andrew F, Hilton, Sarah K, DeWitt, William S
Format: Article
Language:English
Subjects:
Analysis
Bayes Theorem
Computer Simulation
Epistasis, Genetic
Evolution, Molecular
Likelihood Functions
Methods
Models, Genetic
Phylogeny
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Summary:Abstract Likelihood-based phylogenetic inference posits a probabilistic model of character state change along branches of a phylogenetic tree. These models typically assume statistical independence of sites in the sequence alignment. This is a restrictive assumption that facilitates computational tractability, but ignores how epistasis, the effect of genetic background on mutational effects, influences the evolution of functional sequences. We consider the effect of using a misspecified site-independent model on the accuracy of Bayesian phylogenetic inference in the setting of pairwise-site epistasis. Previous work has shown that as alignment length increases, tree reconstruction accuracy also increases. Here, we present a simulation study demonstrating that accuracy increases with alignment size even if the additional sites are epistatically coupled. We introduce an alignment-based test statistic that is a diagnostic for pairwise epistasis and can be used in posterior predictive checks.
ISSN:1537-1719
0737-4038
1537-1719
DOI:10.1093/molbev/msab163