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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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Autores principales: Belinky, Frida, Ganguly, Ishan, Poliakov, Eugenia, Yurchenko, Vyacheslav, Rogozin, Igor B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918605/
https://www.ncbi.nlm.nih.gov/pubmed/33672790
http://dx.doi.org/10.3390/ijms22041876
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author Belinky, Frida
Ganguly, Ishan
Poliakov, Eugenia
Yurchenko, Vyacheslav
Rogozin, Igor B.
author_facet Belinky, Frida
Ganguly, Ishan
Poliakov, Eugenia
Yurchenko, Vyacheslav
Rogozin, Igor B.
author_sort Belinky, Frida
collection PubMed
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.
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spelling pubmed-79186052021-03-02 Analysis of Stop Codons within Prokaryotic Protein-Coding Genes Suggests Frequent Readthrough Events Belinky, Frida Ganguly, Ishan Poliakov, Eugenia Yurchenko, Vyacheslav Rogozin, Igor B. Int J Mol Sci Article 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. MDPI 2021-02-14 /pmc/articles/PMC7918605/ /pubmed/33672790 http://dx.doi.org/10.3390/ijms22041876 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Belinky, Frida
Ganguly, Ishan
Poliakov, Eugenia
Yurchenko, Vyacheslav
Rogozin, Igor B.
Analysis of Stop Codons within Prokaryotic Protein-Coding Genes Suggests Frequent Readthrough Events
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918605/
https://www.ncbi.nlm.nih.gov/pubmed/33672790
http://dx.doi.org/10.3390/ijms22041876
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