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SARS-CoV-2 has been mutating since it was first sequenced in early January 2020. Here, we analyze 45,494 complete SARS-CoV-2 geneome sequences in the world to understand their mutations. Among them, 12,754 sequences are from the United States. Our analysis suggests the presence of four substrains and eleven top mutations in the United States. These eleven top mutations belong to 3 disconnected groups. The first and second groups consisting of 5 and 8 concurrent mutations are prevailing, while the other group with three concurrent mutations gradually fades out. Moreover, we reveal that female immune systems are more active than those of males in responding to SARS-CoV-2 infections. One of the top mutations, 27964C > T-(S24L) on ORF8, has an unusually strong gender dependence. Based on the analysis of all mutations on the spike protein, we uncover that two of four SARS-CoV-2 substrains in the United States become potentially more infectious.

 

The transmission and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of paramount importance in controlling and combating the coronavirus disease 2019 (COVID-19) pandemic. Currently, over 15,000 SARS-CoV-2 single mutations have been recorded, which have a great impact on the development of diagnostics, vaccines, antibody therapies, and drugs. However, little is known about SARS-CoV-2’s evolutionary characteristics and general trend. In this work, we present a comprehensive genotyping analysis of existing SARS-CoV-2 mutations. We reveal that host immune response via APOBEC and ADAR gene editing gives rise to near 65% of recorded mutations. Additionally, we show that children under age five and the elderly may be at high risk from COVID-19 because of their overreaction to the viral infection. Moreover, we uncover that populations of Oceania and Africa react significantly more intensively to SARS-CoV-2 infection than those of Europe and Asia, which may explain why African Americans were shown to be at increased risk of dying from COVID-19, in addition to their high risk of COVID-19 infection caused by systemic health and social inequities. Finally, our study indicates that for two viral genome sequences of the same origin, their evolution order may be determined from the ratio of mutation type, C > T over T > C. 

Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 15 140 genome samples collected up to June 1, 2020, we report that SARS-CoV-2 has undergone 8309 single mutations which can be clustered into six subtypes. We introduce mutation ratio and mutation h-index to characterize the protein conservativeness and unveil that SARS-CoV-2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS-CoV-2 nucleocapsid protein, spike protein, and papain-like protease are relatively nonconservative. In particular, we have identified mutations on 40% of nucleotides in the nucleocapsid gene in the population level, signaling potential impacts on the ongoing development of COVID-19 diagnosis, vaccines, and antibody and small-molecular drugs.