RT Journal Article SR Electronic T1 Robustness of phylogenetic inference to model misspecification caused by pairwise epistasis JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.11.17.387365 DO 10.1101/2020.11.17.387365 A1 Magee, Andrew F. A1 Hilton, Sarah K. A1 DeWitt, William S. YR 2020 UL http://biorxiv.org/content/early/2020/11/17/2020.11.17.387365.abstract AB 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 pair-wise epistasis and can be used in posterior predictive checks.Competing Interest StatementThe authors have declared no competing interest.