No evidence for widespread positive selection on double substitutions within codons in primates and yeasts.

Autor:	Belinky F; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, United States., Bykova A; Life Science Research Centre, Faculty of Science, University of Ostrava, Ostrava, Czech Republic., Yurchenko V; Life Science Research Centre, Faculty of Science, University of Ostrava, Ostrava, Czech Republic., Rogozin IB; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2022 Sep 09; Vol. 13, pp. 991249. Date of Electronic Publication: 2022 Sep 09 (Print Publication: 2022).
DOI:	10.3389/fgene.2022.991249
Abstrakt:	Nucleotide substitutions in protein-coding genes can be divided into synonymous (S) and non-synonymous (N) ones that alter amino acids (including nonsense mutations causing stop codons). The S substitutions are expected to have little effect on function. The N substitutions almost always are affected by strong purifying selection that eliminates them from evolving populations. However, additional mutations of nearby bases can modulate the deleterious effect of single N substitutions and, thus, could be subjected to the positive selection. This effect has been demonstrated for mutations in the serine codons, stop codons and double N substitutions in prokaryotes. In all abovementioned cases, a novel technique was applied that allows elucidating the effects of selection on double substitutions considering mutational biases. Here, we applied the same technique to study double N substitutions in eukaryotic lineages of primates and yeast. We identified markedly fewer cases of purifying selection relative to prokaryotes and no evidence of codon double substitutions under positive selection. This is consistent with previous studies of serine codons in primates and yeast. In general, the obtained results strongly suggest that there are major differences between studied pro- and eukaryotes; double substitutions in primates and yeasts largely reflect mutational biases and are not hallmarks of selection. This is especially important in the context of detection of positive selection in codons because it has been suggested that multiple mutations in codons cause false inferences of lineage-specific site positive selection. It is likely that this concern is applicable to previously studied prokaryotes but not to primates and yeasts where markedly fewer double substitutions are affected by positive selection. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Belinky, Bykova, Yurchenko and Rogozin.)
Databáze:	MEDLINE
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