ACE2 diversity in placental mammals reveals the evolutionary strategy of SARS-CoV-2
DOI:
https://doi.org/10.1590/SciELOPreprints.34Keywords:
ACE2, placental mammals, SARS-CoV-2, COVID-19, inter and intra-species diversityAbstract
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 is a "generalist" coronavirus for human hosts, but not for other species.
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.
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Copyright (c) 2020 Vinicius Sortica, Bibiana Sampaio de Oliveira Fam, Pedro Vargas-Pinilla, Carlos Eduardo Guerra Amorim, Maria Cátira Bortolini

This work is licensed under a Creative Commons Attribution 4.0 International License.


