Leary, S. orcid.org/0000-0002-6966-2294, Gaudieri, S. orcid.org/0000-0001-6873-0198, Parker, M.D. orcid.org/0000-0003-2999-3870 et al. (17 more authors) (Submitted: 2021) Generation of a novel SARS-CoV-2 sub-genomic RNA due to the R203K/G204R variant in nucleocapsid: homologous recombination has potential to change SARS-CoV-2 at both protein and RNA level. [Preprint - bioRxiv] (Submitted)
Abstract
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Genetic variations across the SARS-CoV-2 genome may influence transmissibility of the virus and the host’s anti-viral immune response, in turn affecting the frequency of variants over-time. In this study, we examined the adjacent amino acid polymorphisms in the nucleocapsid (R203K/G204R) of SARS-CoV-2 that arose on the background of the spike D614G change and describe how strains harboring these changes became dominant circulating strains globally.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Deep sequencing data of SARS-CoV-2 from public databases and from clinical samples were analyzed to identify and map genetic variants and sub-genomic RNA transcripts across the genome.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Sequence analysis suggests that the three adjacent nucleotide changes that result in the K203/R204 variant have arisen by homologous recombination from the core sequence (CS) of the leader transcription-regulating sequence (TRS) rather than by stepwise mutation. The resulting sequence changes generate a novel sub-genomic RNA transcript for the C-terminal dimerization domain of nucleocapsid. Deep sequencing data from 981 clinical samples confirmed the presence of the novel TRS-CS-dimerization domain RNA in individuals with the K203/R204 variant. Quantification of sub-genomic RNA indicates that viruses with the K203/R204 variant may also have increased expression of sub-genomic RNA from other open reading frames.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The finding that homologous recombination from the TRS may have occurred since the introduction of SARS-CoV-2 in humans resulting in both coding changes and novel sub-genomic RNA transcripts suggests this as a mechanism for diversification and adaptation within its new host.</jats:p></jats:sec>
Metadata
Item Type: | Preprint |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Author(s). For reuse permissions, please contact the Author(s). |
Keywords: | Infectious Diseases; Vaccine Related; Biotechnology; Human Genome; Genetics; Pneumonia; Lung; Pneumonia & Influenza; Emerging Infectious Diseases; Biodefense; Prevention; 2.1 Biological and endogenous factors; 2 Aetiology |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection, Immunity and Cardiovascular Disease |
Funding Information: | Funder Grant number National Institute for Health Research IS-BRC-1215-20017 WELLCOME TRUST (THE) 110058/A/15/Z |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 11 May 2023 15:07 |
Last Modified: | 11 May 2023 15:07 |
Published Version: | http://dx.doi.org/10.1101/2020.04.10.029454 |
Status: | Submitted |
Publisher: | Cold Spring Harbor Laboratory |
Identification Number: | 10.1101/2020.04.10.029454 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:198949 |