Atlas of ACE2 gene expression in mammals reveals novel insights in transmission of SARS-Cov-2

Kun Sun; Liuqi Gu; Li Ma; Yunfeng Duan

We first examined the conservation of ACE2 across mammalian species. A snapshot obtained from the UCSC genome browser 32 was shown in Figure 1A , which demonstrated high conservation of ACE2 gene's exons in DNA level. Next we examined the conservation of ACE2 at the peptide level by searching the UniProt database 33 for ACE2 protein sequences in mammals. We limited the analysis to species listed in Methods (plus rats) and discarded duplicate records as well as records with abnormally short sequences (< 300 amino acids), leaving 24 ACE2 protein sequences . CC-BY 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 It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the .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/10.1101/2020.03.30.015644 doi: bioRxiv preprint 8 for subsequent analyses. Pairwise alignment results showed that 23 non-human ACE2 proteins share high level of similarity to the human ACE2 protein, with the identity scores ranging from 78.6% to 85.2% and a median score of 81.9%. Notably, for the two virus-binding hotspots (i.e., the 31th and 353th amino acid) 34 , all the mammals except mice and rats share the same amino acids to the human ACE2 protein (Table S3 in Supplementary data). Surprisingly, in contrast to conventional phylogenetic tree generated using genomic data, the phylogenetic tree based on the ACE2 proteins showed that, cats and dogs were the species closest to human instead of mice among the mammals included in this analysis ( Figure 1B) . Taken together, the conservation analysis showed that ACE2 gene was highly conserved among common mammals at both DNA and peptide levels, suggesting that SARS-CoV-2 can potentially bind to ACE2 proteins in these mammals with high affinity 2 .