Non-adaptive evolution in codon usage of human-origin monkeypox virus.

Monkeypox virus (Mpox) is a zoonotic infectious disease that threatens human and animal health, with a global outbreak of the low-pathogenic Mpox beginning from 2022. In this study, we analyzed the codon usage of Mpox between two clades, Clade-I and Clade-IIb-B, to understand changes in host adaptation. Clade-IIb-B of the Mpox genome underwent non-adaptive evolution making it less adapted to its host than Clade-I. The analysis of individual genes revealed that 48 genes exhibited non-adaptive mutation, while 38 genes underwent adaptive mutations. Genes involved in replication, transcription, and host-modulation exhibited a mix of adaptive and non-adaptive evolutionary patterns. This study also found that the mutations of Mpox led to changes in non-adaptative genes in different organs. Additionally, we found that codon usage of Mpox was less similar to that of up-regulated host genes and more similar to that of down-regulated host genes post-infection, indicating that codon usage affects host gene expression. Overall, the study highlights the non-adaptive changes in codon usage as a potential cause of differences in Mpox virulence and provides insights into the evolutionary and adaptive mechanisms of Mpox and its potential impact on pathogenicity and host adaptation.