Genomic diversity of SARS-CoV-2 can be accelerated by mutations in the nsp14 gene
Kosuke Takada,
Mahoko Takahashi Ueda,
Shintaro Shichinohe,
Yurie Kida,
Chikako Ono,
Yoshiharu Matsuura,
Tokiko Watanabe,
So Nakagawa
Affiliations
Kosuke Takada
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan
Mahoko Takahashi Ueda
Department of Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo, Tokyo 113-8510, Japan
Shintaro Shichinohe
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
Yurie Kida
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
Chikako Ono
Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Center for Infectious Disease Education and Research, Osaka University, Suita, Osaka 565-0871, Japan
Yoshiharu Matsuura
Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Center for Infectious Disease Education and Research, Osaka University, Suita, Osaka 565-0871, Japan
Tokiko Watanabe
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Center for Infectious Disease Education and Research, Osaka University, Suita, Osaka 565-0871, Japan; Center for Advanced Modalities and DDS, Osaka University, Suita, Osaka 565-0871, Japan; Corresponding author
So Nakagawa
Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan; Bioinformation and DDBJ Center, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan; Corresponding author
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.
