Strong evolutionary convergence of receptor-binding protein spike between COVID-19 and SARS-related coronaviruses

Yonghua Wu

We used the CONVERG2 31 program to evaluate the probabilities that the observed convergent and parallel substitutions were due to random chance. A statistical significant p-value may suggest the observed evolutionary convergent sites are less likely attributable to random chance, but instead, favor Darwinian selection as a possible explanation. For the analyses, two different amino acid substitution models, JTT and Poisson, were used. The RBD amino acid sequences of our focal 35 coronavirus genomes were abstracted and aligned using CLUSTAL W 41 program. The phylogenetic relationships among the coronavirus strains studied are given in Fig. 1 Fig. 1 The phylogeny of subgenus Sarbecovirus and 11 genes used in this study. The coronavirus phylogeny follows two published studies 5,6 . 2019-nCoV, 2019 novel coronavirus; SARS-CoV, severe acute respiratory syndrome coronavirus; Bat-SL-CoV, bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses. Genomic organization and the 11 genes annotated in the reference genome of 2019-nCoV (NC_045512) are shown. Red dots represent the numbers of identical or nearly identical amino acid sites found in genes, S and ORF3a, which are shared between SARS-related CoV and COVID-19-related CoV, but are completely or nearly completely distinct from those of their phylogenetic intermediates. The spike (S) protein structure follows one previous study 12 , and its receptor-binding domain (RBD) and receptor-binding motif (RBM) are highlighted. * above branches and their corresponding capital letters (A-L) denote the branches with positive selection signals found in the S gene. Two branches (bold) indicate two evolutionary convergent branches with three convergent amino acid substitutions (blue) and 32 shared parallel amino acid substitutions of spike protein. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.04.975995 doi: bioRxiv preprint Fig. 2 The identical or nearly identical RBM amino acid sites (rectangle) shared between SARS-related CoV and COVID-19-related CoV. These shared amino acids are distinct from that of their phylogenetic intermediates. The phylogeny is the same as in Fig. 1 .