Analysis of Stop Codons within Prokaryotic Protein-Coding Genes Suggests Frequent Readthrough Events
Nonsense mutations turn a coding (sense) codon into an in-frame stop codon that is assumed to result in a truncated protein product. Thus, nonsense substitutions are the hallmark of pseudogenes and are used to identify them. Here we show that in-frame stop codons within bacterial protein-coding gene...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/1876 |
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| author | Frida Belinky Ishan Ganguly Eugenia Poliakov Vyacheslav Yurchenko Igor B. Rogozin |
| author_facet | Frida Belinky Ishan Ganguly Eugenia Poliakov Vyacheslav Yurchenko Igor B. Rogozin |
| author_sort | Frida Belinky |
| collection | DOAJ |
| description | Nonsense mutations turn a coding (sense) codon into an in-frame stop codon that is assumed to result in a truncated protein product. Thus, nonsense substitutions are the hallmark of pseudogenes and are used to identify them. Here we show that in-frame stop codons within bacterial protein-coding genes are widespread. Their evolutionary conservation suggests that many of them are not pseudogenes, since they maintain dN/dS values (ratios of substitution rates at non-synonymous and synonymous sites) significantly lower than 1 (this is a signature of purifying selection in protein-coding regions). We also found that double substitutions in codons—where an intermediate step is a nonsense substitution—show a higher rate of evolution compared to null models, indicating that a stop codon was introduced and then changed back to sense via positive selection. This further supports the notion that nonsense substitutions in bacteria are relatively common and do not necessarily cause pseudogenization. In-frame stop codons may be an important mechanism of regulation: Such codons are likely to cause a substantial decrease of protein expression levels. |
| first_indexed | 2024-03-09T00:53:20Z |
| format | Article |
| id | doaj.art-355ee57a9b6a4fb8a917c555967362a8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:53:20Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-355ee57a9b6a4fb8a917c555967362a82023-12-11T17:02:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224187610.3390/ijms22041876Analysis of Stop Codons within Prokaryotic Protein-Coding Genes Suggests Frequent Readthrough EventsFrida Belinky0Ishan Ganguly1Eugenia Poliakov2Vyacheslav Yurchenko3Igor B. Rogozin4National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USANational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USANational Eye Institute, National Institutes of Health, Bethesda, MD 20892, USALife Science Research Centre, Faculty of Science, University of Ostrava, 710 00 Ostrava, Czech RepublicNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USANonsense mutations turn a coding (sense) codon into an in-frame stop codon that is assumed to result in a truncated protein product. Thus, nonsense substitutions are the hallmark of pseudogenes and are used to identify them. Here we show that in-frame stop codons within bacterial protein-coding genes are widespread. Their evolutionary conservation suggests that many of them are not pseudogenes, since they maintain dN/dS values (ratios of substitution rates at non-synonymous and synonymous sites) significantly lower than 1 (this is a signature of purifying selection in protein-coding regions). We also found that double substitutions in codons—where an intermediate step is a nonsense substitution—show a higher rate of evolution compared to null models, indicating that a stop codon was introduced and then changed back to sense via positive selection. This further supports the notion that nonsense substitutions in bacteria are relatively common and do not necessarily cause pseudogenization. In-frame stop codons may be an important mechanism of regulation: Such codons are likely to cause a substantial decrease of protein expression levels.https://www.mdpi.com/1422-0067/22/4/1876in-fame stop codonexpressionshort-term evolutionpopulation polymorphismnegative selection |
| spellingShingle | Frida Belinky Ishan Ganguly Eugenia Poliakov Vyacheslav Yurchenko Igor B. Rogozin Analysis of Stop Codons within Prokaryotic Protein-Coding Genes Suggests Frequent Readthrough Events International Journal of Molecular Sciences in-fame stop codon expression short-term evolution population polymorphism negative selection |
| title | Analysis of Stop Codons within Prokaryotic Protein-Coding Genes Suggests Frequent Readthrough Events |
| title_full | Analysis of Stop Codons within Prokaryotic Protein-Coding Genes Suggests Frequent Readthrough Events |
| title_fullStr | Analysis of Stop Codons within Prokaryotic Protein-Coding Genes Suggests Frequent Readthrough Events |
| title_full_unstemmed | Analysis of Stop Codons within Prokaryotic Protein-Coding Genes Suggests Frequent Readthrough Events |
| title_short | Analysis of Stop Codons within Prokaryotic Protein-Coding Genes Suggests Frequent Readthrough Events |
| title_sort | analysis of stop codons within prokaryotic protein coding genes suggests frequent readthrough events |
| topic | in-fame stop codon expression short-term evolution population polymorphism negative selection |
| url | https://www.mdpi.com/1422-0067/22/4/1876 |
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