Large-Scale Comparative Analysis of Codon Models Accounting for Protein and Nucleotide Selection.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_FF45CD1C1260
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Large-Scale Comparative Analysis of Codon Models Accounting for Protein and Nucleotide Selection.
Journal
Molecular biology and evolution
Author(s)
Davydov I.I., Salamin N., Robinson-Rechavi M.
ISSN
1537-1719 (Electronic)
ISSN-L
0737-4038
Publication state
Published
Issued date
01/06/2019
Peer-reviewed
Oui
Volume
36
Number
6
Pages
1316-1332
Language
english
Notes
Publication types: Comparative Study ; Evaluation Studies ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
There are numerous sources of variation in the rate of synonymous substitutions inside genes, such as direct selection on the nucleotide sequence, or mutation rate variation. Yet scans for positive selection rely on codon models which incorporate an assumption of effectively neutral synonymous substitution rate, constant between sites of each gene. Here we perform a large-scale comparison of approaches which incorporate codon substitution rate variation and propose our own simple yet effective modification of existing models. We find strong effects of substitution rate variation on positive selection inference. More than 70% of the genes detected by the classical branch-site model are presumably false positives caused by the incorrect assumption of uniform synonymous substitution rate. We propose a new model which is strongly favored by the data while remaining computationally tractable. With the new model we can capture signatures of nucleotide level selection acting on translation initiation and on splicing sites within the coding region. Finally, we show that rate variation is highest in the highly recombining regions, and we propose that recombination and mutation rate variation, such as high CpG mutation rate, are the two main sources of nucleotide rate variation. Although we detect fewer genes under positive selection in Drosophila than without rate variation, the genes which we detect contain a stronger signal of adaptation of dynein, which could be associated with Wolbachia infection. We provide software to perform positive selection analysis using the new model.
Keywords
Animals, Codon, Computer Simulation, Drosophila/genetics, Models, Genetic, Mutation Rate, Recombination, Genetic, Selection, Genetic, Silent Mutation, Vertebrates/genetics, codon models, positive selection, substitution rate variation, synonymous substitutions
Pubmed
Web of science
Open Access
Yes
Create date
04/03/2019 15:26
Last modification date
15/01/2021 7:12
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