Comparative genomic analysis reveals varying levels of mammalian adaptation to coronavirus infections.

TitleComparative genomic analysis reveals varying levels of mammalian adaptation to coronavirus infections.
Publication TypeJournal Article
Year of Publication2021
AuthorsKing, SB, Singh, M
JournalPLoS Comput Biol
Date Published2021 11
KeywordsAdaptation, Physiological, Amino Acid Substitution, Angiotensin-Converting Enzyme 2, Animals, CD13 Antigens, Common Cold, Computational Biology, Coronavirus 229E, Human, Coronavirus Infections, COVID-19, Evolution, Molecular, Genomics, Host Microbial Interactions, Host Specificity, Humans, Mammals, Phylogeny, Protein Interaction Domains and Motifs, Receptors, Virus, SARS-CoV-2, Selection, Genetic, Spike Glycoprotein, Coronavirus, Virus Internalization

<p>Severe acute respiratory coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is of zoonotic origin. Evolutionary analyses assessing whether coronaviruses similar to SARS-CoV-2 infected ancestral species of modern-day animal hosts could be useful in identifying additional reservoirs of potentially dangerous coronaviruses. We reasoned that if a clade of species has been repeatedly exposed to a virus, then their proteins relevant for viral entry may exhibit adaptations that affect host susceptibility or response. We perform comparative analyses across the mammalian phylogeny of angiotensin-converting enzyme 2 (ACE2), the cellular receptor for SARS-CoV-2, in order to uncover evidence for selection acting at its binding interface with the SARS-CoV-2 spike protein. We uncover that in rodents there is evidence for adaptive amino acid substitutions at positions comprising the ACE2-spike interaction interface, whereas the variation within ACE2 proteins in primates and some other mammalian clades is not consistent with evolutionary adaptations. We also analyze aminopeptidase N (APN), the receptor for the human coronavirus 229E, a virus that causes the common cold, and find evidence for adaptation in primates. Altogether, our results suggest that the rodent and primate lineages may have had ancient exposures to viruses similar to SARS-CoV-2 and HCoV-229E, respectively.</p>

Alternate JournalPLoS Comput Biol
PubMed ID34793437
PubMed Central IDPMC8601562
Grant ListR01 GM076275 / GM / NIGMS NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States