Mutational spectrum of SARS-CoV-2 during the global pandemic

Kijong Yi,Su Yeon Kim,Taewoo Kim,Young Seok Ju,Thomas Bleazard,Jeonghwan Youk

doi:10.1038/s12276-021-00658-z

Abstract

Viruses accumulate mutations under the influence of natural selection and host–virus interactions. Through a systematic comparison of 351,525 full viral genome sequences collected during the recent COVID-19 pandemic, we reveal the spectrum of SARS-CoV-2 mutations. Unlike those of other viruses, the mutational spectrum of SARS-CoV-2 exhibits extreme asymmetry, with a much higher rate of C>U than U>C substitutions, as well as a higher rate of G>U than U>G substitutions. This suggests directional genome sequence evolution during transmission. The substantial asymmetry and directionality of the mutational spectrum enable pseudotemporal tracing of SARS-CoV-2 without prior information about the root sequence, collection time, and sampling region. This shows that the viral genome sequences collected in Asia are similar to the original genome sequence. Adjusted estimation of the dN/dS ratio accounting for the asymmetrical mutational spectrum also shows evidence of negative selection on viral genes, consistent with previous reports. Our findings provide deep insights into the mutational processes in SARS-CoV-2 viral infection and advance the understanding of the history and future evolution of the virus.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading rapidly and globally[1,2]
We investigated whether the asymmetry of the mutational spectrum is the outcome of selection pressure on infected human cells
Mutational signature in the natural relatives of SARS-CoV-2 We investigated whether spectrum asymmetry is present in long-term fixation in close relatives of SARS-CoV-2, such as bat coronaviruses (RaTG13 and RmYN02) and a pangolin coronavirus recently sequenced from Guangdong and Guanxi, China[4,5,6,7]

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading rapidly and globally[1,2]. SARS-CoV-2 belongs to the subgenus Sarbecovirus, a branch of Betacoronavirus in the Coronaviridae family[3]. Recent comparative studies proposed bats[4,5] and pangolins[6,7,8] as possible natural reservoirs of the virus. Acquisition of new mutations in viral genomes and natural selection acting on the resultant phenotypic diversity are the two constituent processes of viral evolution[9]. Understanding the genome changes of SARS-CoV-2 during the recent outbreak and their proper interpretations are critical for developing preventive, diagnostic, and therapeutic strategies against the virus. Hundreds of thousands of SARS-CoV-2 genomes have been sequenced[10,11], interpretations of the mutations as a whole have not been conducted

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Results

Conclusion