Abstract
Mpox (Monkeypox) is a zoonotic disease caused by mpox virus (MPXV). A multi-country MPXV outbreak in non-endemic demographics was identified in May 2022. A systematic evaluation of MPXV evolutionary trajectory and genetic diversity could be a timely addition to the MPXV diagnostics and prophylaxis. Herein, we integrated a systematic evolution analysis including phylogenomic and phylogeographic, followed by an in-depth analysis of the adaptive evolution and amino acid variations in type I interferon binding protein (IFNα/βBP). Mutations in IFNα/βBP protein may impair its binding capacity, affecting the MPXV immune evasion strategy. Based on the equilibrated data, we found an evolutionary rate of 7.75 × 10-5 substitutions/site/year, and an earlier original time (2021.25) of the clade IIb. We further discovered significant genetic variations in MPXV genomes from different regions and obtained six plausible spread trajectories from its intricate viral flow network, implying that North America might have acted as a bridge for the spread of MPXV from Africa to other continents. We identified two amino acids under positive selection in the Rifampicin resistance protein and extracellular enveloped virus (EEV) type-I membrane glycoprotein, indicating a role in adaptive evolution. Our research sheds light on the emergence, dispersal, and adaptive evolution of MPXV, providing theoretical support for mitigating and containing its expansion.