Codon-Substitution Models for Detecting Molecular Adaptation at Individual Sites Along Specific Lineages

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ID: 294562
2002
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Abstract
The nonsynonymous (amino acid–altering) to synonymous (silent) substitution rate ratio (ω = dN/dS) provides a measure of natural selection at the protein level, with ω = 1, >1, and <1, indicating neutral evolution, purifying selection, and positive selection, respectively. Previous studies that used this measure to detect positive selection have often taken an approach of pairwise comparison, estimating substitution rates by averaging over all sites in the protein. As most amino acids in a functional protein are under structural and functional constraints and adaptive evolution probably affects only a few sites at a few time points, this approach of averaging rates over sites and over time has little power. Previously, we developed codon-based substitution models that allow the ω ratio to vary either among lineages or among sites. In this paper we extend previous models to allow the ω ratio to vary both among sites and among lineages and implement the new models in the likelihood framework. These models may be useful for identifying positive selection along prespecified lineages that affects only a few sites in the protein. We apply those branch-site models as well as previous branch- and site-specific models to three data sets: the lysozyme genes from primates, the tumor suppressor BRCA1 genes from primates, and the phytochrome (PHY) gene family in angiosperms. Positive selection is detected in the lysozyme and BRCA genes by both the new and the old models. However, only the new models detected positive selection acting on lineages after gene duplication in the PHY gene family. Additional tests on several data sets suggest that the new models may be useful in detecting positive selection after gene duplication in gene family evolution.
Reference Key
openalex_W2029549914 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Ziheng Yang, Rasmus Nielsen
Journal molecular biology and evolution
Year 2002
DOI
10.1093/oxfordjournals.molbev.a004148
URL
Keywords Keywords not found

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