Comprehensive evolution and molecular characteristics of a large number of SARS-CoV-2 genomes reveal its epidemic trends

Abstract

Objectives: To further reveal the phylogenetic evolution and molecular characteristics of the whole genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on a large number of genomes and provide a basis for the prevention and treatment of SARS-CoV-2.

Methods: Various evolution analysis methods were employed.

Results: The estimated ratio of the rates of non-synonymous to synonymous changes (Ka/Ks) of SARS-CoV-2 was 1.008 or 1.094 based on 622 or 3624 SARS-CoV-2 genomes and nine key specific sites of high linkage, and four major haplotypes were found: H1, H2, H3 and H4. The results of Ka/Ks, detected population size and development trends of each major haplotype showed that H3 and H4 subgroups were going through a purify evolution and almost disappeared after detection, indicating that they might have existed for a long time. The H1 and H2 subgroups were going through a near neutral or neutral evolution and globally increased with time, and the frequency of H1 was generally high in Europe and correlated with the death rate (r >0.37), suggesting that these two haplotypes might relate to the infectivity or pathogenicity of SARS-CoV-2.

Conclusions: Several key specific sites and haplotypes related to the infectivity or pathogenicity of SARS-CoV-2, and the possible earlier origin time and place of SARS-CoV-2 were indicated based on the evolution and epidemiology of 16,373 SARS-CoV-2 genomes.

Keywords: Classification; Evolution; Haplotype; SARS-CoV-2.

Fig. 1

Phylogenetic tree and clusters of 622 SARS-CoV-2 genomes. The 622 sequences were clustered into three clusters: Cluster 1 was mainly from North America, Cluster 2 was from regions all over the world, and Cluster 3 was mainly from Europe.

Fig. 2

Linkage disequilibrium plot of haplotypes of the nine specific sites. A. The plot for 622 genome sequences; B. The plot for 3624 genome sequences.

Fig. 3

The frequencies of both the nine specific sites and haplotypes. The frequencies of the nine specific sites (A) and haplotypes (B) in each country for 3624 genomes.

Fig. 4

The characteristics of haplotype subgroups. A. The numbers of haplotypes of the nine specific sites for 16,373 genomes with clear collection data detected in each country in chronological order; B. The whole genome mutations in each major haplotype subgroup.

Fig. 5

Phylogenetic network of haplotype subgroups for 3624 genomes. The network was inferred by POPART using the TCS method. Each colored vertex represents a haplotype, with different colors indicating the different sampling areas. Hatch marks along the edge indicate the number of mutations. Small black circles within the network indicate unsampled haplotypes. H1-H5 subgroups are pointed out according to haplotypes of the nine specific sites, and other small subgroups are not especially pointed out.

Fig. 6

The correlation between death rates and frequencies of both the nine specific sites and haplotypes.