The receptor binding domain of SARS-CoV-2 spike protein is the result of an ancestral recombination between the bat-CoV RaTG13 and the pangolin-CoV MP789

BMC Res Notes. 2020 Aug 27;13(1):398. doi: 10.1186/s13104-020-05242-8.

Abstract

Objective: In December 2019 a novel coronavirus (SARS-CoV-2) that is causing the current COVID-19 pandemic was identified in Wuhan, China. Many questions have been raised about its origin and adaptation to humans. In the present work we performed a genetic analysis of the Spike glycoprotein (S) of SARS-CoV-2 and other related coronaviruses (CoVs) isolated from different hosts in order to trace the evolutionary history of this protein and the adaptation of SARS-CoV-2 to humans.

Results: Based on the sequence analysis of the S gene, we suggest that the origin of SARS-CoV-2 is the result of recombination events between bat and pangolin CoVs. The hybrid SARS-CoV-2 ancestor jumped to humans and has been maintained by natural selection. Although the S protein of RaTG13 bat CoV has a high nucleotide identity with the S protein of SARS-CoV-2, the phylogenetic tree and the haplotype network suggest a non-direct parental relationship between these CoVs. Moreover, it is likely that the basic function of the receptor-binding domain (RBD) of S protein was acquired by the SARS-CoV-2 from the MP789 pangolin CoV by recombination and it has been highly conserved.

Keywords: Genealogy; Molecular evolution; Natural selection; Recombination; SARS-CoV-2; Spike glycoprotein.

MeSH terms

  • Adaptation, Biological / genetics
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Betacoronavirus / genetics*
  • Binding Sites / genetics
  • Chiroptera / virology
  • Coronaviridae / genetics*
  • Eutheria / virology
  • Evolution, Molecular
  • Furin / metabolism
  • Host Specificity
  • Humans
  • Peptidyl-Dipeptidase A / metabolism
  • Phylogeny
  • Recombination, Genetic*
  • SARS-CoV-2
  • Selection, Genetic
  • Spike Glycoprotein, Coronavirus / genetics*
  • Spike Glycoprotein, Coronavirus / metabolism

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Furin