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bioRxiv · 10.64898/2026.08.14.744968

OmegaSwitch: Bayesian Markov-Modulated Codon Models for Estimating dN/dS

DeMontigny, W. C.·Delwiche, C. F.
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Abstract

Selective pressures can vary across both sites and evolutionary lineages; however, most codon models accommodate heterogeneity along only one of these dimensions and require the number of selective regimes to be specified in advance. Here, we introduce OmegaSwitch, a Bayesian phylogenetic software framework for inferring changes in the nonsynonymous-to-synonymous substitution-rate ratio (dN/dS) across sites and through evolutionary time. We implement a Markov-modulated codon model in which lineages transition among discrete dN/dS regimes and use reversible-jump Markov chain Monte Carlo to infer the number of regimes simultaneously. We further develop a Dirichlet-process mixture extension that allows the parameters governing these time-heterogeneous processes to vary among sites. Ancestral sampling produces joint posterior distributions of dN/dS across sites and nodes of the phylogeny, enabling lineage- and site-specific summaries with quantified uncertainty. Simulation analyses showed that both the posterior intervals for dN/dS and the number of evolutionary regimes were well calibrated under both models. We demonstrate OmegaSwitch using vertebrate alpha- and beta-globins. OmegaSwitch therefore provides a flexible Bayesian framework for investigating how selective pressures vary across protein-coding sequences and phylogenetic history.

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DeMontigny, W. C., Delwiche, C. F.. 2026-08-19. OmegaSwitch: Bayesian Markov-Modulated Codon Models for Estimating dN/dS. https://doi.org/10.64898/2026.08.14.744968

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