Mutations of SARS-CoV-2 nsp14 exhibit strong association with increased genome-wide mutation load

PeerJ

article

Doğa Eskier¹  Aslı Suner³  Yavuz Oktay¹  Gökhan Karakülah¹ 

[1] Izmir Biomedicine and Genome Center;Izmir International Biomedicine and Genome Institute, Dokuz Eylül University;Department of Biostatistics and Medical Informatics, Faculty of Medicine, Ege University;Faculty of Medicine, Department of Medical Biology, Dokuz Eylül University

关键词: SARS-CoV-2;    COVID-19;    nsp14;    3′-5′ exonuclease;    RNA-dependent RNA polymerase;    RdRp;    Mutation rate;   

DOI  :  10.7717/peerj.10181

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

SARS-CoV-2 is a betacoronavirus responsible for COVID-19, a pandemic with global impact that first emerged in late 2019. Since then, the viral genome has shown considerable variance as the disease spread across the world, in part due to the zoonotic origins of the virus and the human host adaptation process. As a virus with an RNA genome that codes for its own genomic replication proteins, mutations in these proteins can significantly impact the variance rate of the genome, affecting both the survival and infection rate of the virus, and attempts at combating the disease. In this study, we analyzed the mutation densities of viral isolates carrying frequently observed mutations for four proteins in the RNA synthesis complex over time in comparison to wildtype isolates. Our observations suggest mutations in nsp14, an error-correcting exonuclease protein, have the strongest association with increased mutation load without selective pressure and across the genome, compared to nsp7, nsp8 and nsp12, which form the core polymerase complex. We propose nsp14 as a priority research target for understanding genomic variance rate in SARS-CoV-2 isolates and nsp14 mutations as potential predictors for high mutability strains.

【 授权许可】

CC BY