Comprehensive Genomics Investigation of Neboviruses Reveals Distinct Codon Usage Patterns and Host Specificity.

(NeVs) from the family have been linked to enteric diseases in bovines and have been detected worldwide. As viruses rely entirely on the cellular machinery of the host for replication, their ability to thrive in a specific host is greatly impacted by the specific codon usage preferences. Here, we systematically analyzed the codon usage bias in NeVs to explore the genetic and evolutionary patterns. Relative Synonymous Codon Usage and Effective Number of Codon analyses indicated a marginally lower codon usage bias in NeVs, predominantly influenced by the nucleotide compositional constraints. Nonetheless, NeVs showed a higher codon usage bias for codons containing G/C at the third codon position. The neutrality plot analysis revealed natural selection as the primary factor that shaped the codon usage bias in both the VP1 (82%) and VP2 (57%) genes of NeVs. Furthermore, the NeVs showed a highly comparable codon usage pattern to bovines, as reflected through Codon Adaptation Index and Relative Codon Deoptimization Index analyses. Notably, yak NeVs showed considerably different nucleotide compositional constraints and mutational pressure compared to bovine NeVs, which appear to be predominantly host-driven. This study sheds light on the genetic mechanism driving NeVs' adaptability, evolution, and fitness to their host species.