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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.
  • Zhao L; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK.
  • Hall M; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK.
  • de Cesare M; Human Technopole, Milan, Italy.
  • MacIntyre-Cockett G; Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Lythgoe K; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK.
  • Fraser C; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK.
  • Bonsall D; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK.
  • Golubchik T; Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Ferretti L; Sydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, University of Sydney, Sydney NSW 2006, Australia.
Proc Biol Sci ; 289(1987): 20221747, 2022 11 30.
Article in English | MEDLINE | ID: covidwho-2115857
ABSTRACT
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies Topics: Variants Limits: Humans Language: English Journal: Proc Biol Sci Journal subject: Biology Year: 2022 Document Type: Article Affiliation country: Rspb.2022.1747

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies Topics: Variants Limits: Humans Language: English Journal: Proc Biol Sci Journal subject: Biology Year: 2022 Document Type: Article Affiliation country: Rspb.2022.1747