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

To determine whether it was likely to be interactions with coronavirus driving the 347 evolution of ACE2 we used MEME 19 to infer the residues under selection across the mammal 348 phylogeny, in just bats and in non-bat mammals and used a Fisher's exact test to determine 349 whether residues that interact with SARS-CoV, SARS-CoV-2 or HCoV-NL63 23 were more likely 350 to be under selection than other residues in ACE2. Only codons that showed variation (e.g. 351 more than one amino acid across all 198 species) and that were present in humans were 352 considered in the Fisher's exact test. We used a p < 0.05 cutoff for inferring selection at each 353 site via MEME but some results were shaper when using a p < 0.1 cutoff, likely due to the 354 reduction in loss of statistical power (Table S3) . (Table S4 ). As described in the 371 author/funder. All rights reserved. No reuse allowed without permission.