Abstract
Many viruses that cause serious diseases in humans and animals, including the betacoronaviruses (beta-CoVs), such as SARS-CoV, MERS-CoV, and the recently identified SARS-CoV-2, have natural reservoirs in bats. Because these viruses rely entirely on the host cellular machinery for survival, their evolution is likely to be guided by the link between the codon usage of the virus and that of its host. As a result, specific cellular microenvironments of the diverse hosts and/or host tissues imprint peculiar molecular signatures in virus genomes. Our study is aimed at deciphering some of these signatures. Using a variety of genetic methods we demonstrated that trends in codon usage across chiroptera-hosted CoVs are collaboratively driven by geographically different host-species and temporal-spatial distribution. We not only found that chiroptera-hosted CoVs are the ancestors of SARS-CoV-2, but we also revealed that SARS-CoV-2 has the codon usage characteristics similar to those seen in CoVs infecting the Rhinolophus sp. Surprisingly, the envelope gene of beta-CoVs infecting Rhinolophus sp., including SARS-CoV-2, had extremely high CpG levels, which appears to be an evolutionarily conserved trait. The dissection of the furin cleavage site of various CoVs infecting hosts revealed host-specific preferences for arginine codons; however, arginine is encoded by a wider variety of synonymous codons in the murine CoV (MHV-A59) furin cleavage site. Our findings also highlight the latent diversity of CoVs in mammals that has yet to be fully explored.
Highlights
IntroductionBats belong to the Chiroptera order, which is the second largest mammalian order after rodents and is the natural reservoir host for many key emerging and re-emerging viruses that cause serious human diseases [1,2,3]
Increasing evidence suggests that bats are the reservoir host for alpha- and beta-CoVs that can infect a wide range of mammals, including humans, but gamma- and delta-CoVs are mostly found in birds [7]
We found that the mean evolutionary diversity between and within the subgenera of the chiroptera-hosted CoVs was 0.44 ± 0.11 and 0.16 ± 0.03, respectively
Summary
Bats belong to the Chiroptera order, which is the second largest mammalian order after rodents and is the natural reservoir host for many key emerging and re-emerging viruses that cause serious human diseases [1,2,3]. Despite the fact that several of these viruses are lethal to humans, they are not known to produce clinical illnesses in bats. Megabats, which are mostly frugivorous (fruit eaters), and microbats, who are mostly insectivorous (insects-eater), are the two suborders of bats. Bats have lately been divided into two suborders based on molecular studies: Yinpterochiroptera (which includes megabats and 4.0/). In addition to henipaviruses (Hendra and Nipah viruses) causing severe and often fatal diseases [5], coronaviruses (CoVs) are among the several chiroptera-borne viruses that have recently attracted the attention of the general and scientific communities
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