Exceptional diversity and selection pressure on SARS-CoV and SARS-CoV-2 host receptor in bats compared to other mammals

Hannah K. Frank; David Enard; Scott D. Boyd

when considering sites under selection at p < 0.1, residues that contact SARS-CoV-2 do indeed 99 appear to be more likely to be under selection than other residues in the gene, likely due to the 100 reduction in statistical power loss (MEME p < 0.1, Fisher's exact test, pall trees < 0.02). Therefore 101 there is some evidence that the locus is evolving in response to coronaviruses; this is similar to 102 the finding of strong selection in aminopeptidase N (ANPEP) in response to coronaviruses in 103 mammals 18 . However, this pattern is driven by and strengthened in bats; in bats a greater 104 proportion of residues that contact SARS-CoV (MEME p<0.05, Fisher's exact test, pall trees < 105 0.03; MEME p<0.1, Fisher's exact test, pall trees < 0.02; Table S3 ) and SARS-CoV-2 (MEME p < 106 0.05, Fisher's exact test, pall trees < 0.02; MEME p<0.1, Fisher's exact test, pall trees < 0.0004; The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.20.051656 doi: bioRxiv preprint 6 selection in non-bat mammals. Increased sampling can improve the ability of MEME to detect 112 selection at individual sites 19 . Because our dataset of bat sequences is smaller than our 113 mammalian dataset, it further strengthens our conclusion that bats are under positive selection 114 in contact residues. Across all mammals, positions 24 and 42 were under selection (Table S2; 5 115 trees, MEME, p < 0.05), but in bats positions 27, 31, 35 and 354 (Table S2 , 5 trees, MEME, p < 116 0.05) and 30, 38, 329 and 393 (Table S2 , 5 trees, MEME, p < 0.1) were additionally under 117 positive selection while positions 45 (Table S2 , 5 trees, MEME, p < 0.05) and 353 (Table S2, 5 118 trees, MEME, p < 0.1) were under selection in non-bat mammals but not bats.