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

• Main Authors: King, S.B (Author), Singh, M. (Author)
• Format: Article
• Language: English
• Published: Public Library of Science 2021
• Subjects: adaptation; Adaptation, Physiological; amino acid substitution; Amino Acid Substitution; angiotensin converting enzyme 2; Angiotensin-Converting Enzyme 2; animal; Animals; Article; binding affinity; biology; CD13 Antigens; cladistics; cold; common cold; Common Cold; comparative genomics; comparative study; Computational Biology; controlled study; Coronavirus 229E, Human; coronavirus disease 2019; Coronavirus infection; Coronavirus Infections; coronavirus spike glycoprotein; COVID-19; Evolution, Molecular; evolutionary adaptation; genetic selection; genetics; genomics; Genomics; Host Microbial Interactions; host range; Host Specificity; host susceptibility; human; Human coronavirus 229E; Humans; mammal; mammalian genetics; Mammals; microsomal aminopeptidase; molecular evolution; molecular phylogeny; nonhuman; phylogeny; Phylogeny; physiology; primate; protein domain; protein interaction; Protein Interaction Domains and Motifs; Receptors, Virus; SARS-CoV-2; Selection, Genetic; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus; spike protein, SARS-CoV-2; virology; virus entry; Virus Internalization; virus receptor
• Online Access: View Fulltext in Publisher

 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 SARSCoV- 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. © 2021 King, Singh. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.