Evolution and molecular characteristics of SARS-CoV-2 genome

In the evolution analysis of 622 complete human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes with high quality, the estimated Ka/Ks ratio of SARS-CoV-2 is 1.008, which is significantly higher than that of SARS-CoV and MERS-CoV, and the time to the most recent common ancestor (tMRCA) of SARS-CoV-2 is inferred in late September 2019 (95% CI: 2019/08/28-2019/10/26), which indicating that SARS-CoV-2 may have completed a positive selection pressure of the cross-host evolution in the early stage and be going through a neutral evolution at present. In addition, no-root phylogenetic tree of the 622 SARS-CoV-2 genomes were constructed by maximum likelihood (ML) with the bootstrap value of 100. According to the phylogenetic trees, all genomes were divided into Cluster 1 to 3, in which genomes were mainly from North America, global and Europe respectively. Further we find 9 key specific sites of highly linkage which play a decisive role in the classification of each cluster. Among them, 3 and 4 sites of almost complete linkage are the specific sites for Cluster 1 and Cluster 3 respectively. Notably the frequencies of haplotype TTTG and H1 are generally high in European countries and correlated to death rate (r>0.4) based on more than 3500 SARS-CoV-2 genomes, which indicated that the haplotypes might be related to pathogenicity of SARS-CoV-2 and need to be addressed. According to haplotype changes in chronological order, the H3 haplotype subgroup disappeared soon after detection, while H1 haplotype subgroup was globally increasing with time. The evolution and molecular characteristics of more than 3500 genomic sequences provided a new perspective for revealing the epidemiology mechanism of SARS-CoV-2 and coping with SARS-CoV-2 effectively.