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

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

We highlight two mutations, 427N and 436Y, conserved in human SARS-CoV, SARS-CoV-2 and human- Table 4 ). Interestingly, a mouse-adapted SARS virus showed a mutation at position 436 (Y436H) that enhanced the replication and pathogenesis in mice 16, 17 , indicating that this change may have an effect in host tropism. It is noteworthy that unlike 436Y, 455I and 466N, the 427N mutation was present in the closest strains not . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.10.942748 doi: bioRxiv preprint involved in the recombination event (KY770859 and KJ473816), suggesting that it appeared in their MRCA through point mutation. Our ancestral state reconstructions also suggest that 427N has appeared at two other independent times in bat SARS-like CoVs, and only at external branches (sequences JX993988 and JX993987; Supplementary Figure 5 ). Other bat isolates with the 427N allele, such as Rs7327, Rs4874 and Rs4231, are known to co-opt the human ACE2 receptor 18 , further reinforcing the role of 427N as an adaptive mutation for the interaction with ACE2.