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

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. SARS-CoV-2: Monitoring coronavirus mutations Sequencing the genetic material of >350,000 samples of the SARS-CoV-2 virus responsible for the COVID-19 pandemic has revealed details of the spectrum of mutations occurring in the recent viral transmission. The analysis was performed by researchers in South Korea and the UK, led by Young Seok Ju at the Korea Advanced Institute for Science and Technology, Daejeon. The results confirm that mutations in the SARS-CoV-2 genome are being shaped in a specific pattern: the nucleic acid bases cytosine and guanine have been replaced by uracil much more often than its reverse. Overall, the genome diversity of SARS-CoV-2 has not yet reached equilibrium, suggesting that the virus entered the human population very recently and is currently evolving rapidly. The findings enhance understanding of the history of the virus and help predict possibilities for its future evolution.