Evolutionary analysis and population dynamics in the global transmission of Kaposi’s sarcoma-associated herpesvirus

With the widespread prevalence of Kaposi's sarcoma-associated herpesvirus (KSHV) globally, particularly in sub-Saharan Africa and the Mediterranean region, the open reading frame (ORF) K1 gene, a key gene for distinguishing different subtypes of KSHV, has been extensively studied for its diversity and sequence variations. In this study, we collected K1 gene sequences representing subtypes of KSHV worldwide in order to assess the global distribution of KSHV subtypes and to investigate the recombination and selection history of KSHV. Recombination and gene flow analysis indicated a minimum average recombination rate of 0.41 per site for the K1 gene. Recombination analysis indicated that 11 major recombination events had occurred, predominantly in subtypes A and C, while subtype B showed minimal involvement in recombination processes, consistent with the gene flow analysis. Using tip-dating methods, we estimated that the most recent common ancestor of KSHV emerged in the 12th century, while the currently globally prevalent subtypes appeared within the past three centuries. Its recent origin and rapid evolution indicate that KSHV is now undergoing strong selection and is in the process of adaptation.