Massive‐scale genomic analysis reveals SARS‐CoV‐2 mutation characteristics and evolutionary trends

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic resulted in significant societal costs. Hence, an in‐depth understanding of SARS‐CoV‐2 virus mutation and its evolution will help determine the direction of the COVID‐19 pandemic. In this study, we identified 296,728 de novo mutations in more than 2,800,000 high‐quality SARS‐CoV‐2 genomes. All possible factors affecting the mutation frequency of SARS‐CoV‐2 in human hosts were analyzed, including zinc finger antiviral proteins, sequence context, amino acid change, and translation efficiency. As a result, we proposed that when adenine (A) and tyrosine (T) bases are in the context of AM (M stands for adenine or cytosine) or TA motif, A or T base has lower mutation frequency. Furthermore, we hypothesized that translation efficiency can affect the mutation frequency of the third position of the codon by the selection, which explains why SARS‐CoV‐2 prefers AT3 codons usage. In addition, we found a host‐specific asymmetric dinucleotide mutation frequency in the SARS‐CoV‐2 genome, which provides a new basis for determining the origin of the SARS‐CoV‐2. Finally, we summarize all possible factors affecting mutation frequency and provide insights into the mutation characteristics and evolutionary trends of SARS‐CoV‐2. Impact statement In this study, we analyzed the possible factors affecting mutations in more than 2,800,000 high‐quality severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) genomes. To our knowledge we are the first to propose that when the A or T base conforms to AM or TA motif, the A or T base has a lower mutation frequency;and subsequently, translation efficiency can affect the mutation frequency from C/G to A/T on the third position of the codon by the selection. We found significant host‐specific asymmetric mutations at dinucleotide sites. In addition, we also identified the characteristics of SARS‐CoV‐2 mutations and hypothesized the evolutionary trends of the virus in the human host. These findings are valuable for predicting the development of the COVID‐19 pandemic and bring to light new hypotheses regarding the origin of SARS‐CoV‐2.