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 host-cell infection. We performed a 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 for analysis 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.
Our goal was to describe in more detail the evolutionary history of Gamma and two
derived lineages (P.1.1 and P.1.2), which are part of the arms race that
SARS-CoV-2 wages with its host. A total of 4,977 sequences of the Gamma strain
of SARS-CoV-2 from Brazil were analyzed. We detected 194 sites under positive
selection in 12 genes/ORFs:
Spike, N, M, E, ORF1a, ORF1b, ORF3, ORF6,
ORF7a, ORF7b, ORF8,
and
ORF10
. Some diagnostic
sites for Gamma lacked a signature of positive selection in our study, but these
were not fixed, apparently escaping the action of purifying selection. Our
network analyses revealed branches leading to expanding haplotypes with sites
under selection only detected when P.1.1 and P.1.2 were considered. The P.1.2
exclusive haplotype H_5 originated from a non-synonymous mutational step
(H3509Y) in H_1 of
ORF1a.
The selected allele, 3509Y,
represents an adaptive novelty involving
ORF1a
of P.1. Finally,
we discuss how phenomena such as epistasis and antagonistic pleiotropy could
limit the emergence of new alleles (and combinations thereof) in SARS-COV-2
lineages, maintaining infectivity in humans, while providing rapid response
capabilities to face the arms race triggered by host immuneresponses.
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.
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