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The mutational spectrum of SARS-CoV-2 genomic and antigenomic RNA

The raw material for viral evolution is provided by intra-host mutations occurring during replication, transcription or post-transcription. Replication and transcription of Coronaviridae proceed through the synthesis of negative-sense ‘antigenomes’ acting as templates for positive-sense genomic and...

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Autores principales: Zhao, Lele, Hall, Matthew, de Cesare, Mariateresa, MacIntyre-Cockett, George, Lythgoe, Katrina, Fraser, Christophe, Bonsall, David, Golubchik, Tanya, Ferretti, Luca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9667359/
https://www.ncbi.nlm.nih.gov/pubmed/36382519
http://dx.doi.org/10.1098/rspb.2022.1747
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author Zhao, Lele
Hall, Matthew
de Cesare, Mariateresa
MacIntyre-Cockett, George
Lythgoe, Katrina
Fraser, Christophe
Bonsall, David
Golubchik, Tanya
Ferretti, Luca
author_facet Zhao, Lele
Hall, Matthew
de Cesare, Mariateresa
MacIntyre-Cockett, George
Lythgoe, Katrina
Fraser, Christophe
Bonsall, David
Golubchik, Tanya
Ferretti, Luca
author_sort Zhao, Lele
collection PubMed
description The raw material for viral evolution is provided by intra-host mutations occurring during replication, transcription or post-transcription. Replication and transcription of Coronaviridae proceed through the synthesis of negative-sense ‘antigenomes’ acting as templates for positive-sense genomic and subgenomic RNA. Hence, mutations in the genomes of SARS-CoV-2 and other coronaviruses can occur during (and after) the synthesis of either negative-sense or positive-sense RNA, with potentially distinct patterns and consequences. We explored for the first time the mutational spectrum of SARS-CoV-2 (sub)genomic and anti(sub)genomic RNA. We use a high-quality deep sequencing dataset produced using a quantitative strand-aware sequencing method, controlled for artefacts and sequencing errors, and scrutinized for accurate detection of within-host diversity. The nucleotide differences between negative- and positive-sense strand consensus vary between patients and do not show dependence on age or sex. Similarities and differences in mutational patterns between within-host minor variants on the two RNA strands suggested strand-specific mutations or editing by host deaminases and oxidative damage. We observe generally neutral and slight negative selection on the negative strand, contrasting with purifying selection in ORF1a, ORF1b and S genes of the positive strand of the genome.
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spelling pubmed-96673592022-11-21 The mutational spectrum of SARS-CoV-2 genomic and antigenomic RNA Zhao, Lele Hall, Matthew de Cesare, Mariateresa MacIntyre-Cockett, George Lythgoe, Katrina Fraser, Christophe Bonsall, David Golubchik, Tanya Ferretti, Luca Proc Biol Sci Special Feature The raw material for viral evolution is provided by intra-host mutations occurring during replication, transcription or post-transcription. Replication and transcription of Coronaviridae proceed through the synthesis of negative-sense ‘antigenomes’ acting as templates for positive-sense genomic and subgenomic RNA. Hence, mutations in the genomes of SARS-CoV-2 and other coronaviruses can occur during (and after) the synthesis of either negative-sense or positive-sense RNA, with potentially distinct patterns and consequences. We explored for the first time the mutational spectrum of SARS-CoV-2 (sub)genomic and anti(sub)genomic RNA. We use a high-quality deep sequencing dataset produced using a quantitative strand-aware sequencing method, controlled for artefacts and sequencing errors, and scrutinized for accurate detection of within-host diversity. The nucleotide differences between negative- and positive-sense strand consensus vary between patients and do not show dependence on age or sex. Similarities and differences in mutational patterns between within-host minor variants on the two RNA strands suggested strand-specific mutations or editing by host deaminases and oxidative damage. We observe generally neutral and slight negative selection on the negative strand, contrasting with purifying selection in ORF1a, ORF1b and S genes of the positive strand of the genome. The Royal Society 2022-11-30 2022-11-16 /pmc/articles/PMC9667359/ /pubmed/36382519 http://dx.doi.org/10.1098/rspb.2022.1747 Text en © 2022 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, provided the original author and source are credited.
spellingShingle Special Feature
Zhao, Lele
Hall, Matthew
de Cesare, Mariateresa
MacIntyre-Cockett, George
Lythgoe, Katrina
Fraser, Christophe
Bonsall, David
Golubchik, Tanya
Ferretti, Luca
The mutational spectrum of SARS-CoV-2 genomic and antigenomic RNA
title The mutational spectrum of SARS-CoV-2 genomic and antigenomic RNA
title_full The mutational spectrum of SARS-CoV-2 genomic and antigenomic RNA
title_fullStr The mutational spectrum of SARS-CoV-2 genomic and antigenomic RNA
title_full_unstemmed The mutational spectrum of SARS-CoV-2 genomic and antigenomic RNA
title_short The mutational spectrum of SARS-CoV-2 genomic and antigenomic RNA
title_sort mutational spectrum of sars-cov-2 genomic and antigenomic rna
topic Special Feature
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9667359/
https://www.ncbi.nlm.nih.gov/pubmed/36382519
http://dx.doi.org/10.1098/rspb.2022.1747
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