iScience
Volume 26, Issue 3, 17 March 2023, 106210
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Article
Genomic diversity of SARS-CoV-2 can be accelerated by mutations in the nsp14 gene

https://doi.org/10.1016/j.isci.2023.106210Get rights and content
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Highlights

  • Amino acids of nonstructural protein 14 (nsp14) are well conserved in coronaviruses

  • P203L in nsp14 was not detected among coronaviruses but observed in SARS-CoV-2

  • Genome analysis suggested P203L nsp14 variants have a higher evolutionary rate

  • In vivo studies confirmed that the P203L nsp14 accelerates genomic diversity

Summary

Coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), encode a proofreading exonuclease, nonstructural protein 14 (nsp14), that helps ensure replication competence at a low evolutionary rate compared with other RNA viruses. In the current pandemic, SARS-CoV-2 has accumulated diverse genomic mutations including in nsp14. Here, to clarify whether amino acid substitutions in nsp14 affect the genomic diversity and evolution of SARS-CoV-2, we searched for amino acid substitutions in nature that may interfere with nsp14 function. We found that viruses carrying a proline-to-leucine change at position 203 (P203L) have a high evolutionary rate and that a recombinant SARS-CoV-2 virus with the P203L mutation acquired more diverse genomic mutations than wild-type virus during its replication in hamsters. Our findings suggest that substitutions, such as P203L, in nsp14 may accelerate the genomic diversity of SARS-CoV-2, contributing to virus evolution during the pandemic.

Subject areas

Virology
Evolutionary biology

Data and code availability

  • RNA-seq data have been deposited at DDBJ Sequence Read Archive (DRA) with the following accession numbers: DRR411740 - DRR411753. The GISAID accession numbers used in this study are listed in STAR Methods.

  • This paper does not report original code.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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