Recombination and Positive Selection Differentially Shaped the Diversity of Betacoronavirus Subgenera

The Betacoronavirus genus of mammal-infecting viruses includes three subgenera (Sarbecovirus, Embecovirus, and Merbecovirus), in which most known human coronaviruses, including SARS-CoV-2, cluster. Coronaviruses are prone to host shifts, with recombination and positive selection possibly contributing to their high zoonotic potential. We analyzed the role of these two forces in the evolution of viruses belonging to the Betacoronavirus genus. The results showed that recombination has been pervasive during sarbecovirus evolution, and it is more widespread in this subgenus compared to the other two. In both sarbecoviruses and merbecoviruses, recombination hotspots are clearly observed. Conversely, positive selection was a less prominent force in sarbecoviruses compared to embecoviruses and merbecoviruses and targeted distinct genomic regions in the three subgenera, with S being the major target in sarbecoviruses alone. Overall, the results herein indicate that Betacoronavirus subgenera evolved along different trajectories, which might recapitulate their host preferences or reflect the origins of the presently available coronavirus sequences.