Zhao, Lele, Hall, Matthew, de Cesare, Mariateresa, MacIntyre-Cockett, George, Lythgoe, Katrina, Fraser, Christophe, Bonsall, David, Golubchik, Tanya, Ferretti, Luca, The COVID-19 Genomics UK (COG-UK) Consortium, , Bashton, Matthew, Smith, Darren, Nelson, Andrew, Young, Greg and McCann, Clare (2022) The mutational spectrum of SARS-CoV-2 genomic and antigenomic RNA. Proceedings of the Royal Society B: Biological Sciences, 289 (1987). p. 20221747. ISSN 0962-8452
|
Text
rspb.2022.1747.pdf - Published Version Available under License Creative Commons Attribution 4.0. Download (789kB) | Preview |
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.
| Item Type: | Article |
|---|---|
| Additional Information: | Matthew Bashton, Andrew Nelson, Clare McCann, Greg Young and Darren Smith are members of the COVID-19 Genomics UK consortium. Funding information: COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) (grant code: MC_PC_19027), and Genome Research Limited, operating as the Wellcome Sanger Institute. This work was supported by a Li Ka Shing Foundation Grant awarded to C.F. The research was supported by the Wellcome Trust Core Award grant no. 203141/Z/16/Z with funding from the NIHR Oxford BRC. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. |
| Uncontrolled Keywords: | SARS-CoV-2, antigenomes,mutational spectrum, RNA editing |
| Subjects: | C500 Microbiology C700 Molecular Biology, Biophysics and Biochemistry |
| Department: | Faculties > Health and Life Sciences > Applied Sciences |
| Depositing User: | Elena Carlaw |
| Date Deposited: | 22 Feb 2023 15:19 |
| Last Modified: | 22 Feb 2023 15:19 |
| URI: | https://nrl.northumbria.ac.uk/id/eprint/51475 |
Actions (login required)
 |
View Item |
Downloads
Downloads per month over past year
