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Stop Codon Usage as a Window into Genome Evolution: Mutation, Selection, Biased Gene Conversion and the TAG Paradox

Protein coding genes terminate with one of three stop codons (TAA, TGA, or TAG) that, like synonymous codons, are not employed equally. With TGA and TAG having identical nucleotide content, analysis of their differential usage provides an unusual window into the forces operating on what are ostensib...

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Autores principales: Ho, Alexander T, Hurst, Laurence D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348620/
https://www.ncbi.nlm.nih.gov/pubmed/35867377
http://dx.doi.org/10.1093/gbe/evac115
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author Ho, Alexander T
Hurst, Laurence D
author_facet Ho, Alexander T
Hurst, Laurence D
author_sort Ho, Alexander T
collection PubMed
description Protein coding genes terminate with one of three stop codons (TAA, TGA, or TAG) that, like synonymous codons, are not employed equally. With TGA and TAG having identical nucleotide content, analysis of their differential usage provides an unusual window into the forces operating on what are ostensibly functionally identical residues. Across genomes and between isochores within the human genome, TGA usage increases with G + C content but, with a common G + C → A + T mutation bias, this cannot be explained by mutation bias-drift equilibrium. Increased usage of TGA in G + C-rich genomes or genomic regions is also unlikely to reflect selection for the optimal stop codon, as TAA appears to be universally optimal, probably because it has the lowest read-through rate. Despite TAA being favored by selection and mutation bias, as with codon usage bias G + C pressure is the prime determinant of between-species TGA usage trends. In species with strong G + C-biased gene conversion (gBGC), such as mammals and birds, the high usage and conservation of TGA is best explained by an A + T → G + C repair bias. How to explain TGA enrichment in other G + C-rich genomes is less clear. Enigmatically, across bacterial and archaeal species and between human isochores TAG usage is mostly unresponsive to G + C pressure. This unresponsiveness we dub the TAG paradox as currently no mutational, selective, or gBGC model provides a well-supported explanation. That TAG does increase with G + C usage across eukaryotes makes the usage elsewhere yet more enigmatic. We suggest resolution of the TAG paradox may provide insights into either an unknown but common selective preference (probably at the DNA/RNA level) or an unrecognized complexity to the action of gBGC.
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spelling pubmed-93486202022-08-04 Stop Codon Usage as a Window into Genome Evolution: Mutation, Selection, Biased Gene Conversion and the TAG Paradox Ho, Alexander T Hurst, Laurence D Genome Biol Evol Review Protein coding genes terminate with one of three stop codons (TAA, TGA, or TAG) that, like synonymous codons, are not employed equally. With TGA and TAG having identical nucleotide content, analysis of their differential usage provides an unusual window into the forces operating on what are ostensibly functionally identical residues. Across genomes and between isochores within the human genome, TGA usage increases with G + C content but, with a common G + C → A + T mutation bias, this cannot be explained by mutation bias-drift equilibrium. Increased usage of TGA in G + C-rich genomes or genomic regions is also unlikely to reflect selection for the optimal stop codon, as TAA appears to be universally optimal, probably because it has the lowest read-through rate. Despite TAA being favored by selection and mutation bias, as with codon usage bias G + C pressure is the prime determinant of between-species TGA usage trends. In species with strong G + C-biased gene conversion (gBGC), such as mammals and birds, the high usage and conservation of TGA is best explained by an A + T → G + C repair bias. How to explain TGA enrichment in other G + C-rich genomes is less clear. Enigmatically, across bacterial and archaeal species and between human isochores TAG usage is mostly unresponsive to G + C pressure. This unresponsiveness we dub the TAG paradox as currently no mutational, selective, or gBGC model provides a well-supported explanation. That TAG does increase with G + C usage across eukaryotes makes the usage elsewhere yet more enigmatic. We suggest resolution of the TAG paradox may provide insights into either an unknown but common selective preference (probably at the DNA/RNA level) or an unrecognized complexity to the action of gBGC. Oxford University Press 2022-07-22 /pmc/articles/PMC9348620/ /pubmed/35867377 http://dx.doi.org/10.1093/gbe/evac115 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Ho, Alexander T
Hurst, Laurence D
Stop Codon Usage as a Window into Genome Evolution: Mutation, Selection, Biased Gene Conversion and the TAG Paradox
title Stop Codon Usage as a Window into Genome Evolution: Mutation, Selection, Biased Gene Conversion and the TAG Paradox
title_full Stop Codon Usage as a Window into Genome Evolution: Mutation, Selection, Biased Gene Conversion and the TAG Paradox
title_fullStr Stop Codon Usage as a Window into Genome Evolution: Mutation, Selection, Biased Gene Conversion and the TAG Paradox
title_full_unstemmed Stop Codon Usage as a Window into Genome Evolution: Mutation, Selection, Biased Gene Conversion and the TAG Paradox
title_short Stop Codon Usage as a Window into Genome Evolution: Mutation, Selection, Biased Gene Conversion and the TAG Paradox
title_sort stop codon usage as a window into genome evolution: mutation, selection, biased gene conversion and the tag paradox
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348620/
https://www.ncbi.nlm.nih.gov/pubmed/35867377
http://dx.doi.org/10.1093/gbe/evac115
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