No evidence for widespread positive selection on double substitutions within codons in primates and yeasts
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 affecte...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.991249/full |
| _version_ | 1811210445293355008 |
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| author | Frida Belinky Anastassia Bykova Vyacheslav Yurchenko Igor B. Rogozin |
| author_facet | Frida Belinky Anastassia Bykova Vyacheslav Yurchenko Igor B. Rogozin |
| author_sort | Frida Belinky |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T04:55:41Z |
| format | Article |
| id | doaj.art-5fc803d1c2a44897b932ad76de7fa064 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-12T04:55:41Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-5fc803d1c2a44897b932ad76de7fa0642022-12-22T03:47:08ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-09-011310.3389/fgene.2022.991249991249No evidence for widespread positive selection on double substitutions within codons in primates and yeastsFrida Belinky0Anastassia Bykova1Vyacheslav Yurchenko2Igor B. Rogozin3National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, United StatesLife Science Research Centre, Faculty of Science, University of Ostrava, Ostrava, Czech RepublicLife Science Research Centre, Faculty of Science, University of Ostrava, Ostrava, Czech RepublicNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, United StatesNucleotide 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.https://www.frontiersin.org/articles/10.3389/fgene.2022.991249/fullnatural selectiontandem mutationsshort-term evolutionneutral evolutiondouble substitutionspositive selection |
| spellingShingle | Frida Belinky Anastassia Bykova Vyacheslav Yurchenko Igor B. Rogozin No evidence for widespread positive selection on double substitutions within codons in primates and yeasts Frontiers in Genetics natural selection tandem mutations short-term evolution neutral evolution double substitutions positive selection |
| title | No evidence for widespread positive selection on double substitutions within codons in primates and yeasts |
| title_full | No evidence for widespread positive selection on double substitutions within codons in primates and yeasts |
| title_fullStr | No evidence for widespread positive selection on double substitutions within codons in primates and yeasts |
| title_full_unstemmed | No evidence for widespread positive selection on double substitutions within codons in primates and yeasts |
| title_short | No evidence for widespread positive selection on double substitutions within codons in primates and yeasts |
| title_sort | no evidence for widespread positive selection on double substitutions within codons in primates and yeasts |
| topic | natural selection tandem mutations short-term evolution neutral evolution double substitutions positive selection |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.991249/full |
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