Recombination and lineage-specific mutations led to the emergence of SARS-CoV-2

Juan Angel Patino-Galindo; Ioan Filip; Mohammed AlQuraishi; Raul Rabadan

The distributions of nonsynonymous and 4-fold degenerate site changes between SARS-CoV-2 and RaTG13 across the viral genome highlighted two regions with significant enrichment of nonsynonymous changes (adjusted p-val. < 10 -5 and p-val. < 10 -3 for the first and second regions respectively, binomial test on sliding windows of 267 amino acids) (Figure 4b ). The first region, with windows starting between positions 801 and 1067 in the Orf1a gene in our analysis, spans the non-structural proteins (nsp) 2 and 3 that were previously reported to accrue a high number of mutations between bat and SARS CoVs 19 and includes the ubiquitin-like domain 1, a glutamic acid-rich hypervariable region, and the SARS-unique domain of nsp3 20 that is critical to replication and transcription 21, 22 . The second region that we found with high divergence from the RaTG13 bat virus contained 27 substitutions in the Spike protein, of which 20 were located in the RBD (Supplementary Table 5 ). There was no significant enrichment in mutations observed at 4-fold degenerate sites ( Supplementary Figures 7-10 ).