Abstract
The hunt for the immediate non-human host of SARS-CoV-2 has centered on bats of the genus Rhinolophus. We explored the phylogenetic predictions of two models of viral transmission, the Spillover Model and the Circulation Model and suggest that the Spillover Model can be eliminated. The Circulation Model suggests that viral transmission occurs among susceptible hosts irrespective of their phylogenetic relationships. Susceptibility could be mediated by the ACE2 gene (important for viral docking) and we constructed a phylogeny of this gene for 159 mammal species, finding a phylogenetic pattern consistent with established mammalian relationships. The tree indicates that viral transfer occurs over large evolutionary distances. Although lacking consensus, some studies identify a virus from a particular R. affinis individual (RaTG13) as being most closely related phylogenetically to human SARS-CoV-2. However, other R. affinis harbor viruses that are relatively unrelated to human viruses, and viruses found in this species exhibit sequence differences of up to 20%, suggesting multiple transfers over time. There is little correspondence between viral and host (bat) species limits or phylogenetic relationships. An ACE2 phylogeny for Rhinolophus followed species limits, unlike the pattern in the viral phylogeny indicating that phylogenetic similarity of ACE2 is not a predictor of viral transmission at the bat species level. The Circulation Model could be modified to apply to any individual of any species of Rhinolophus; more individuals and species must be examined.
Highlights
Numerous publications have employed phylogenetic analyses of viral sequences and the mammalian host species in which they were found to identify the most likely source of the SARS CoV-2 virus that led to the COVID-19 pandemic
To explain the predicted phylogenetic outcome, the Circulation Model would have to assume that compatible ACE2 genotypes are phylogenetically randomly distributed among species. We examined this assumption by constructing a phylogenetic tree for the ACE2 gene for 159 mammal species, finding that the gene tree is consistent with mammalian phylogeny (Supplementary Figure 1)–closely related mammal species have phylogenetically closely related ACE2 sequences irrespective of their viral lineages
To explore further the relationship between viral phylogeny and the bat ACE2 gene tree, we constructed a phylogenetic hypothesis for species of Rhinolophus (Figure 2); most available sequences come from two species (R. affinis, R. sinicus) often implicated as candidates for transmission to humans [5]
Summary
Numerous publications have employed phylogenetic analyses of viral sequences and the mammalian host species in which they were found to identify the most likely source of the SARS CoV-2 virus that led to the COVID-19 pandemic. Phylogenetic Models of Viral Transmission a virus whose sequence is most closely related phylogenetically to those circulating in humans is the likely source of the human COVID-19 pandemic. In the Spike protein gene tree of Frutos et al [4], the viral sequence from Rhinolophus affinis (intermediate horseshoe bat) was closest to those recovered from eight humans.
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