Comparative analysis of codon usage bias revealed natural selection-driven evolution and host adaptation of...

The infectious haematopoietic necrosis virus (IHNV) is an important threat for global salmonid aquaculture, particularly Oncorhynchus mykiss. Understanding molecular mechanisms of evolution and host adaptation is crucial. This study comparatively analyses codon usage bias (CUB) between IHNV genotypes and their relations to host adaptation and evolutionary forces. Phylogenetic analysis of IHNV reveals topological differences based on whole-genome and G gene. Temporal analysis mapped major genotypic diversification to the 1950s-1970s. At the whole-genome and G gene levels, the most frequently preferred codons were related to the encoding of Leu (CTC), Ser (TCC), Pro (CCC), and Thr (ACC) across all genotypes (RSCU > 1.6). All data points fall below the expected effective number of codons (ENC) curve in ENC-plot. Codon usage for every genotype departs from the PR2-plot origin (0.5, 0.5) to varying extents in both the G gene and the whole genome. For whole-genome datasets, the selection contribution metric values for genotypes U, J, and E were 45.22%, 89.23%, and 99.52%, respectively, in Neutrality plots. Correspondingly, the selection contribution metric for G gene genotypes L, J, U, M, and E were 56.49%, 68.49%, 93.57%, 96.45%, and 85.52%, respectively. The CpG, GpC, GpT, TpT, and TpA were markedly underrepresented (Pxy < 0.78), while CpA, GpA, and TpC were overrepresented in both the G gene and the whole genome (Pxy > 1.25). Codon adaptation index analysis shows a conserved optimal adaptation of all IHNV genotypes to salmonid hosts (rainbow trout and Chinook salmon). Bayesian skyline reconstruction shows genotype-specific population dynamics with expansion phases associated to intensive aquaculture. These results provide a molecular framework for understanding IHNV epidemiology and host specificity.