Molecular Evolution of Human Coronavirus Genomes

Diego Forni, Rachele Cagliani, Mario Clerici, Manuela Sironi

Research output: Contribution to journalArticlepeer-review


Human coronaviruses (HCoVs), including SARS-CoV and MERS-CoV, are zoonotic pathogens that originated in wild animals. HCoVs have large genomes that encode a fixed array of structural and nonstructural components, as well as a variety of accessory proteins that differ in number and sequence even among closely related CoVs. Thus, in addition to recombination and mutation, HCoV genomes evolve through gene gains and losses. In this review we summarize recent findings on the molecular evolution of HCoV genomes, with special attention to recombination and adaptive events that generated new viral species and contributed to host shifts and to HCoV emergence. Human coronaviruses (HCoVs) are zoonotic pathogens with large and complex genomes. Some HCoV accessory proteins were acquired from host genes, and some were lost or split during HCoV evolution. Most likely SARS-CoV ORF8 became dispensable during the shift to the human/civet host.HCoV spike proteins adapted to use diverse cellular receptors. This occurred by divergence followed, in some cases, by convergent evolution to bind the same receptor.Recombination and positive selection shaped the diversity of CoV genomes, especially the S gene. Positive selection in the S gene of MERS-CoV and related CoVs mainly acted on the heptad repeats.In MERS-CoV and other lineage C beta-CoVs, positive selection targeted the nonstructural components, particularly ORF1a. Most adaptive events occurred in nsp3, which acts as a viral protease and contributes to suppression of interferon responses.

Original languageEnglish
JournalTrends in Microbiology
Early online dateOct 19 2016
Publication statusE-pub ahead of print - Oct 19 2016


  • Gene gain/loss
  • Host shift
  • Human coronavirus
  • Molecular evolution
  • Positive selection
  • Recombination

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)
  • Infectious Diseases
  • Virology


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