ArticleBiology direct2017
Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models.
Article in Biology direct, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed.
- Article
- Molecular characterization and gene expression of the HSP90 gene family in Cyprinus carpio and Oreochromis niloticus under thermal stress.Fish physiology and biochemistry · 2026Article
- Separating selection from mutation in antibody language models.bioRxiv : the preprint server for biology · 2025Article
- Accurate prediction of substitution rates at protein sites with a mutation-selection model.Scientific reports · 2025Article
- A Sitewise Model of Natural Selection on Individual Antibodies via a Transformer-Encoder.Molecular biology and evolution · 2025Article
- Estimating the proportion of beneficial mutations that are not adaptive in mammals.PLoS genetics · 2024Article
- Increased Positive Selection in Highly Recombining Genes Does not Necessarily Reflect an Evolutionary Advantage of Recombination.Molecular biology and evolution · 2024Article
- Systematically testing human HMBS missense variants to reveal mechanism and pathogenic variation.American journal of human genetics · 2023Article
- Genes and sites under adaptation at the phylogenetic scale also exhibit adaptation at the population-genetic scale.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Systematically testing human HMBS missense variants to reveal mechanism and pathogenic variation.bioRxiv : the preprint server for biology · 2023Article
- Co-expression network analyses of anthocyanin biosynthesis genes in Ruellia (Wild Petunias; Acanthaceae).BMC ecology and evolution · 2022Article
- An Improved Codon Modeling Approach for Accurate Estimation of the Mutation Bias.Molecular biology and evolution · 2022Article
- OBI: A computational tool for the analysis and systematization of the positive selection in proteins.MethodsX · 2022Article
- Evolutionary dissection of monkeypox virus: Positive Darwinian selection drives the adaptation of virus-host interaction proteins.Frontiers in cellular and infection microbiology · 2022Article
- Inferring Long-Term Effective Population Size with Mutation-Selection Models.Molecular biology and evolution · 2021Article
- A Bayesian Mutation-Selection Framework for Detecting Site-Specific Adaptive Evolution in Protein-Coding Genes.Molecular biology and evolution · 2021Article
- Article
- Integrated structural and evolutionary analysis reveals common mechanisms underlying adaptive evolution in mammals.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans.eLife · 2019Article
- Detecting amino acid preference shifts with codon-level mutation-selection mixture models.BMC evolutionary biology · 2019Article
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Abstract
backgroundSites of positive selection are identified by comparing observed evolutionary patterns to those expected under a null model for evolution in the absence of such selection. For protein-coding genes, the most common null model is that nonsynonymous and synonymous mutations fix at equal rates; this unrealistic model has limited power to detect many interesting forms of selection.
resultsI describe a new approach that uses a null model based on experimental measurements of a gene's site-specific amino-acid preferences generated by deep mutational scanning in the lab. This null model makes it possible to identify both diversifying selection for repeated amino-acid change and differential selection for mutations to amino acids that are unexpected given the measurements made in the lab. I show that this approach identifies sites of adaptive substitutions in four genes (lactamase, Gal4, influenza nucleoprotein, and influenza hemagglutinin) far better than a comparable method that simply compares the rates of nonsynonymous and synonymous substitutions.
conclusionsAs rapid increases in biological data enable increasingly nuanced descriptions of the constraints on individual protein sites, approaches like the one here can improve our ability to identify many interesting forms of selection in natural sequences. REVIEWERS: This article was reviewed by Sebastian Maurer-Stroh, Olivier Tenaillon, and Tal Pupko. All three reviewers are members of the Biology Direct editorial board.
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