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Stop codons in bacteria are not selectively equivalent

BACKGROUND: The evolution and genomic stop codon frequencies have not been rigorously studied with the exception of coding of non-canonical amino acids. Here we study the rate of evolution and frequency distribution of stop codons in bacterial genomes. RESULTS: We show that in bacteria stop codons e...

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Autores principales: Povolotskaya, Inna S, Kondrashov, Fyodor A, Ledda, Alice, Vlasov, Peter K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549826/
https://www.ncbi.nlm.nih.gov/pubmed/22974057
http://dx.doi.org/10.1186/1745-6150-7-30
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author Povolotskaya, Inna S
Kondrashov, Fyodor A
Ledda, Alice
Vlasov, Peter K
author_facet Povolotskaya, Inna S
Kondrashov, Fyodor A
Ledda, Alice
Vlasov, Peter K
author_sort Povolotskaya, Inna S
collection PubMed
description BACKGROUND: The evolution and genomic stop codon frequencies have not been rigorously studied with the exception of coding of non-canonical amino acids. Here we study the rate of evolution and frequency distribution of stop codons in bacterial genomes. RESULTS: We show that in bacteria stop codons evolve slower than synonymous sites, suggesting the action of weak negative selection. However, the frequency of stop codons relative to genomic nucleotide content indicated that this selection regime is not straightforward. The frequency of TAA and TGA stop codons is GC-content dependent, with TAA decreasing and TGA increasing with GC-content, while TAG frequency is independent of GC-content. Applying a formal, analytical model to these data we found that the relationship between stop codon frequencies and nucleotide content cannot be explained by mutational biases or selection on nucleotide content. However, with weak nucleotide content-dependent selection on TAG, -0.5 < Nes < 1.5, the model fits all of the data and recapitulates the relationship between TAG and nucleotide content. For biologically plausible rates of mutations we show that, in bacteria, TAG stop codon is universally associated with lower fitness, with TAA being the optimal for G-content < 16% while for G-content > 16% TGA has a higher fitness than TAG. CONCLUSIONS: Our data indicate that TAG codon is universally suboptimal in the bacterial lineage, such that TAA is likely to be the preferred stop codon for low GC content while the TGA is the preferred stop codon for high GC content. The optimization of stop codon usage may therefore be useful in genome engineering or gene expression optimization applications. REVIEWERS: This article was reviewed by Michail Gelfand, Arcady Mushegian and Shamil Sunyaev. For the full reviews, please go to the Reviewers’ Comments section.
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spelling pubmed-35498262013-01-23 Stop codons in bacteria are not selectively equivalent Povolotskaya, Inna S Kondrashov, Fyodor A Ledda, Alice Vlasov, Peter K Biol Direct Research BACKGROUND: The evolution and genomic stop codon frequencies have not been rigorously studied with the exception of coding of non-canonical amino acids. Here we study the rate of evolution and frequency distribution of stop codons in bacterial genomes. RESULTS: We show that in bacteria stop codons evolve slower than synonymous sites, suggesting the action of weak negative selection. However, the frequency of stop codons relative to genomic nucleotide content indicated that this selection regime is not straightforward. The frequency of TAA and TGA stop codons is GC-content dependent, with TAA decreasing and TGA increasing with GC-content, while TAG frequency is independent of GC-content. Applying a formal, analytical model to these data we found that the relationship between stop codon frequencies and nucleotide content cannot be explained by mutational biases or selection on nucleotide content. However, with weak nucleotide content-dependent selection on TAG, -0.5 < Nes < 1.5, the model fits all of the data and recapitulates the relationship between TAG and nucleotide content. For biologically plausible rates of mutations we show that, in bacteria, TAG stop codon is universally associated with lower fitness, with TAA being the optimal for G-content < 16% while for G-content > 16% TGA has a higher fitness than TAG. CONCLUSIONS: Our data indicate that TAG codon is universally suboptimal in the bacterial lineage, such that TAA is likely to be the preferred stop codon for low GC content while the TGA is the preferred stop codon for high GC content. The optimization of stop codon usage may therefore be useful in genome engineering or gene expression optimization applications. REVIEWERS: This article was reviewed by Michail Gelfand, Arcady Mushegian and Shamil Sunyaev. For the full reviews, please go to the Reviewers’ Comments section. BioMed Central 2012-09-13 /pmc/articles/PMC3549826/ /pubmed/22974057 http://dx.doi.org/10.1186/1745-6150-7-30 Text en Copyright ©2012 Povolotskaya et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Povolotskaya, Inna S
Kondrashov, Fyodor A
Ledda, Alice
Vlasov, Peter K
Stop codons in bacteria are not selectively equivalent
title Stop codons in bacteria are not selectively equivalent
title_full Stop codons in bacteria are not selectively equivalent
title_fullStr Stop codons in bacteria are not selectively equivalent
title_full_unstemmed Stop codons in bacteria are not selectively equivalent
title_short Stop codons in bacteria are not selectively equivalent
title_sort stop codons in bacteria are not selectively equivalent
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549826/
https://www.ncbi.nlm.nih.gov/pubmed/22974057
http://dx.doi.org/10.1186/1745-6150-7-30
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