Generalizing rate heterogeneity across sites in statistical phylogenetics

Sarah E. Heaps, Tom M W Nye, Richard J. Boys, Tom Williams, Svetlana Cherlin, T. Martin Embley

Research output: Contribution to journalArticle (Academic Journal)

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Abstract

Phylogenetics uses alignments of molecular sequence data to learn about evolutionary trees relating species. Along branches, sequence evolution is modelled using a continuous-time Markov process characterized by an instantaneous rate matrix. Early models assumed the same rate matrix governed substitutions at all sites of the alignment, ignoring variation in evolutionary pressures. Substantial improvements in phylogenetic inference and model fit were achieved by augmenting these models with multiplicative random effects that describe the result of variation in selective constraints and allow sites to evolve at different rates which linearly scale a baseline rate matrix. Motivated by this pioneering work, we consider an extension using a quadratic, rather than linear, transformation. The resulting models allow for variation in the selective coefficients of different types of point mutation at a site in addition to variation in selective constraints. We derive properties of the extended models. For certain non-stationary processes, the extension gives a model that allows variation in sequence composition, both across sites and taxa. We adopt a Bayesian approach, describe an MCMC algorithm for posterior inference and provide software. Our quadratic models are applied to alignments spanning the tree of life and compared with site-homogeneous and linear models.

Original languageEnglish
Number of pages27
JournalStatistical Modelling
Early online date10 Mar 2019
DOIs
Publication statusE-pub ahead of print - 10 Mar 2019

Keywords

  • Across-site rate heterogeneity
  • Compositional heterogeneity
  • multiplicative random effects
  • phylogenetics
  • selective coefficients
  • tree of life

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