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PreprintCC BYbioRxiv

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

  1. 1University of Maryland at College Park

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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BibTeX
@misc{demontigny2026omegaswitch,
  title = {{OmegaSwitch: Bayesian Markov-Modulated Codon Models for Estimating dN/dS}},
  author = {W. C. DeMontigny and C. F. Delwiche},
  howpublished = {bioRxiv},
  year = {2026},
  month = aug,
  doi = {10.64898/2026.08.14.744968},
  url = {https://www.biorxiv.org/content/10.64898/2026.08.14.744968v2},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - OmegaSwitch: Bayesian Markov-Modulated Codon Models for Estimating dN/dS
AU  - W. C. DeMontigny
AU  - C. F. Delwiche
PY  - 2026
DA  - 2026/08/14
PB  - bioRxiv
DO  - 10.64898/2026.08.14.744968
UR  - https://www.biorxiv.org/content/10.64898/2026.08.14.744968v2
AB  - 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.
ER  -