The phylogenomics of evolving virus virulence

How virulence evolves after a virus jumps to a new host species is central to disease emergence. Our current understanding of virulence evolution is based on insights drawn from two perspectives that have developed largely independently: long-standing evolutionary theory based on limited real data examples that often lack a genomic basis, and experimental studies of virulence-determining mutations using cell culture or animal models. A more comprehensive understanding of virulence mutations and their evolution can be achieved by bridging the gap between these two research pathways through the phylogenomic analysis of virus genome sequence data as a guide to experimental study. The virulence of viruses is a major determinant of the health burden of viral infections in humans and other species. In this article, Geoghegan and Holmes discuss how largely disparate research fields — theoretical modelling of virulence evolution and experimental dissection of genetic virulence determinants in laboratory model systems — can be bridged by considering real genomic data of viral evolution in a phylogenetic context. They describe the underlying principles of virulence evolution and how they apply to real-world viral infections and outbreaks of global importance.