The recent emergence of
SARS-CoV-2 is responsible for the current
pandemic of COVID-19, which uses the
human membrane protein ACE2 as a gateway to the host-
cell infection. We perform
comparative genomic analysis of 70 ACE2
placental mammal orthologues to identify variations and contribute to the
understanding of evolutionary dynamics behind this successful adaptation to infect
humans. Our results reveal that 4% of the ACE2 sites are under positive selection, all located in the
catalytic domain, suggesting possibly taxon-specific adaptations related to the ACE2 function, such as
cardiovascular physiology. Considering all variable sites, we selected 30 of them located at the critical ACE2
binding sites to the
SARS-CoV-like
viruses to analyze in more detail. Our results reveal a relatively high diversity of ACE2 between
placental mammal species while showing no polymorphism within
human populations, at least considering the 30 inter-species variable sites. A perfect scenario for
natural selection favored this opportunistic new
coronavirus in its trajectory of infecting
humans. We suggest that
SARS-CoV-2 became a
specialist coronavirus for
human hosts. Differences in the rate of
infection and
mortality could be related to the
innate immune responses, other unknown genetic factors, as well as non-
biological factors.