Recombination hotspots and genetic variability in foot-and-mouth disease virus genomes: a comparative genomic and phylogeographic analysis.

Foot-and-mouth disease virus (FMDV) poses a major threat to the global livestock economy. In this study, we analyzed 951 complete genome sequences of FMDV from 66 countries/regions reported from 1958 to 2023, using phylogenomics, recombination detection, and entropy analysis to elucidate its evolutionary dynamics. The phylogeny confirmed the grouping of isolates within the seven established serotypes (O, A, Asia1, C, SAT1, 2, and 3) with strong geographic clustering, and distinct subgenotypes were identified within serotypes O, A, Asia1, and SAT1. The genetic similarity was high (> 90%) within the serotypes but low (< 75%) between them, with the P1 capsid region showing the highest divergence. Interestingly, 117 probable recombination events were detected, predominantly involving serotypes O (n = 41) and A (n = 38), with 58.1% being inter-serotypic. Recombination hotspots were identified in non-structural regions (P2/P3), and the recombination frequency was markedly higher among the Asian and African isolates. Shannon entropy analysis revealed elevated amino acid variability in the structural proteins, notably VP1, of serotypes O and A. The study demonstrates that recombination is an important driver of FMDV diversity and adaptability, significantly affecting vaccine efficacy and outbreak patterns. These findings emphasize the critical need for global genomic surveillance to inform vaccine selection and control strategies.