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

Two bat families, Rhinolophidae and Hipposideridae, have been associated with SARS-143 related betacoronaviruses 5 , which use the ACE2 molecule as a viral receptor 9 . Interestingly, 144 while we found evidence that Rhinolophidae are under selection in ACE2, we found widespread 145 selection across bats. Branches in the rhinolophid/ hipposiderid clade were not more likely to be 146 under selection than other branches within bats (Fisher's exact test, pall trees > 0.7; Table S4 ) and 147 bat lineages that live outside the predicted range of these viruses (e.g. in the Americas 5 ) are 148 also under positive selection. Therefore, there are still aspects of the bat-coronavirus 149 relationship that we do not fully understand. At least one other coronavirus uses ACE2 to gain 150 entry into the host cell, HCoV-NL63, which may have its origin in bats 22 ; we found some 151 evidence for increased selection in the residues that contact this virus in bats (MEME p < 0.05,