Pan-genome insights into the evolutionary dynamics and functional diversification of genes in monkeypox virus

Monkeypox virus (MPXV) continues to emerge as a global health threat. While genetically diverse, its genomic structure and evolution remain undercharacterized. This study analyzed 157 non-redundant MPXV genomes (subtypes Ia, Ib, IIa, IIb), identifying 183 core and 222 non-core genes via pan-genome analysis—indicative of an open pan-genome. Over half (55.8%) of MPXV genes show gene number variation. Non-core genes exhibit a higher ratio of insertions/deletions compared to core genes. Additionally, selection pressure analysis indicated that non-core genes are more prone to positive selection. Furthermore, interaction analysis revealed that core viral proteins target immune-related human pathways, while non-core proteins engage with viral infection-associated proteins. These results deepen our understanding of MPXV evolution and inform future research directions.