Recombination and selection trajectory of the monkeypox virus during its adaptation in the human population

Abstract Monkeypox, caused by the monkeypox virus (MPXV), was historically confined to West and Central Africa but has now spread globally. Recombination and selection play crucial roles in the evolutionary adaptation of MPXV; however, the evolution of MPXV and its relationship with the recent, ground‐breaking monkeypox epidemic remains poorly understood. To gain insights into the evolutionary dynamics of MPXV, comprehensive in silico recombination and selection analyses were conducted based on MPXV whole genome sequence data. Three types of recombination were identified: five ancestor‐sharing interspecies recombination events, six specific interspecies recombination events and four intraspecies recombination events. The results highlight the prevalent occurrence of recombination in MPXV, with 73.3% occurring in variable regions of the genome. Selection analysis was performed from three dimensions: proteins around recombination regions, proteins from recombinant ancestors and MPXV branches, and whole‐genome gene analysis. Results revealed 2 and 7 proteins under positive selection in the first two dimensions, respectively. These proteins are mainly involved in infection immunity, apoptosis regulation and viral virulence. Whole‐genome analysis detected 25 genes under positive selection, mainly associated with immune response and viral regulation. Understanding their evolutionary patterns will help predict and prevent cross‐species transmission, zoonotic outbreaks and potential human epidemics.