Phylogenetic reconstruction of the initial stages of the spread of the SARS-CoV-2 virus in the Eurasian and American continents by analyzing genomic data

Abstract

Samples from complete genomes of SARS-CoV-2 isolated during the first wave (December 2019-July 2020) of the global COVID-19 pandemic from 21 countries (Asia, Europe, Middle East and America) around the world, were analyzed using the phylogenetic method with molecular clock dating. Results showed that the first cases of COVID-19 in the human population appeared in the period between July and November 2019 in China. The spread of the virus into other countries of the world began in the autumn of 2019. In mid-February 2020, the virus appeared in all the countries we analyzed. During this time, the global population of SARS-CoV-2 was characterized by low levels of the genetic polymorphism, making it difficult to accurately assess the pathways of infection. The rate of evolution of the coding region of the SARS-CoV-2 genome equal to 7.3 × 10^-4 (5.95 × 10^-4-8.68 × 10^-4) nucleotide substitutions per site per year is comparable to those of other human RNA viruses (Measles morbillivirus, Rubella virus, Enterovirus C). SARS-CoV-2 was separated from its known close relative, the bat coronavirus RaTG13 of the genus Betacoronavirus, approximately 15-43 years ago (the end of the 20th century).

Keywords: COVID-19; Evolutionary rate; Genomics; Molecular clock; SARS-CoV-2; Virus spread.

Fig. 1

The undated Maximal Likelihood tree (ML) reconstructed in the IQTREE program. The tree was rooted based on time of the virus isolation with the “residual-mean-squared” method in the TempEst program. The tips names contain information about the country of isolation of the strain, the time of isolation of the strain and the number of days that have passed since the isolation of the first genome.

Fig. 2

The dated phylogenetic tree of SARS-CoV-2 was reconstructed based on complete coding genome regions of viruses isolated from December 2019 to July 2020. Different world regions are marked with colored circles. Dating of the appearance of the first phylogenetic SARS-CoV-2 lineages in each of 21 studied countries is shown at the nodes.

Fig. 3

The distribution of confidence intervals on the time scale shows the time periods of the appearance of SARS-CoV-2 first phylogenetic lineages in studied countries. Results are based on the datasets of 252, 513 and 777 SARS-CoV-2 genomes. The black dotted vertical bar separates the countries’ confidence intervals, which intersect with the confidence interval calculated for China at the initial period of the COVID-19 pandemic.

Fig. 4

Assessment of the relationship between the supports of the topology of nodes and the time of node appearance on the dated Bayesian phylogenetic tree (a - ultrafast bootstrap support, b - Bayesian posterior probability) and histograms of the distribution of the supports of the tree topology (c - ultrafast bootstrap support, d - Bayesian posterior probability).

Fig. 5

Dated evolutionary tree of SARS-CoV-2, and closely related viruses of the genus Betacoronavirus, based on the complete coding regions of their genomes, was reconstructed applying exponential growth population size and relaxed clock with tip-dating (dating of the tree by the time of isolating strains). Numbers at nodes indicate statistical support values of tree topology and confidence intervals of molecular dating.