Parallel molecular evolution and adaptation are important phenomena commonly observed in viruses. Here, we exploit parallel molecular evolution to understand virulence evolution in avian influenza viruses (AIV). Highly-pathogenic AIVs evolve independently from low-pathogenic ancestors via acquisition of polybasic cleavage sites. Why some AIV lineages but not others evolve in this way is unknown. We hypothesise that the parallel emergence of highly-pathogenic AIV may be facilitated by permissive or compensatory mutations occurring across the viral genome. We combine phylogenetic, statistical and structural approaches to discover parallel mutations in AIV genomes associated with the highly-pathogenic phenotype. Parallel mutations were screened using a statistical test of mutation-phenotype association and further evaluated in the contexts of positive selection and protein structure. Our resulting mutational panel may help to reveal new links between virulence evolution and other traits, and raises the possibility of predicting aspects of AIV evolution. Highly pathogenic avian influenza viruses (HPAIV) can evolve via acquisition of polybasic cleavage sites, but the contribution of other mutations remains unclear. Here, the authors combine phylogenetic, statistical and structural approaches, and identify parallel mutations that are associated with HPAIV phenotype.
【저자키워드】 Influenza virus, molecular evolution, viral evolution, phylogenetics,