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A Codon Model for Associating Phenotypic Traits with Altered Selective Patterns of Sequence Evolution

Halabi, Keren, Karin, Eli Levy, Guéguen, Laurent, Mayrose, Itay·2021·Systematic Biology
DOI 10.1093/sysbio/syaa087

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Abstract

Detecting the signature of selection in coding sequences and associating it with shifts in phenotypic states can unveil genes underlying complex traits. Of the various signatures of selection exhibited at the molecular level, changes in the pattern of selection at protein-coding genes have been of main interest. To this end, phylogenetic branch-site codon models are routinely applied to detect changes in selective patterns along specific branches of the phylogeny. Many of these methods rely on a prespecified partition of the phylogeny to branch categories, thus treating the course of trait evolution as fully resolved and assuming that phenotypic transitions have occurred only at speciation events. Here, we present TraitRELAX, a new phylogenetic model that alleviates these strong assumptions by explicitly accounting for the uncertainty in the evolution of both trait and coding sequences. This joint statistical framework enables the detection of changes in selection intensity upon repeated trait transitions. We evaluated the performance of TraitRELAX using simulations and then applied it to two case studies. Using TraitRELAX, we found an intensification of selection in the primate SEMG2 gene in polygynandrous species compared to species of other mating forms, as well as changes in the intensity of purifying selection operating on sixteen bacterial genes upon transitioning from a free-living to an endosymbiotic lifestyle.[Evolutionary selection; intensification; $\gamma $-proteobacteria; genotype–phenotype; relaxation; SEMG2.]

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  • Trait changes do not necessarily occur at the point of speciation, and models that assign whole branches as having a particular trait can cause erroneous inference of selective pressures.

    “Another motivation for more complex models of selective pressure is that trait changes do not necessarily occur at the point of speciation. The models discussed above all implicitly make this assumption as they assign whole branches as having a particular trait, which can cause erroneous inference of the selective pressures acting on a genetic element (Halabi et al. 2021).”

    From From Trees to Traits: A Review of Advances in PhyloG2P Methods and Future Directions (2025) · cites this paper as Halabi et al. 2021

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Authors
Halabi, K., Karin, E. L., Guéguen, L., & Mayrose, I.
Affiliations
  • School of Plant Sciences and Food Security, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
  • Quantitative and Computational Biology, Max-Planck institute for biophysical Chemistry, Göttingen 37077, Germany
  • Université de Lyon, Université Lyon 1, CNRS, Laboratoire de Biométrie et Biologie Evolutive UMR 5558, F-69622 Villeurbanne, France
Venue
Systematic Biology
Publisher
Oxford University Press (OUP)
Published
2020-11-30
Volume
70
Issue
3
Pages
608-622
ISSN
  • 1063-5157
  • 1076-836X
DOI
10.1093/sysbio/syaa087
Cited by
15
References
3
Language
en
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Funders
  • Edmond J. Safra Center for Bioinformatics
  • National Science Foundation-BSF (1655478)
  • Koret-UC Berkeley-Tel Aviv University Initiative in Computational Biology and Bioinformatics

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