Virulence determines the impact a pathogen has on the fitness of its host, yet
current understanding of the evolutionary origins and causes of virulence of
many pathogens is surprisingly incomplete. Here, we explore the evolution of
Marek's disease virus (MDV), a herpesvirus commonly afflicting chickens and
rarely other avian species. The history of MDV in the 20th century represents
an important case study in the evolution of virulence. The severity of MDV
infection in chickens has been rising steadily since the adoption of intensive
farming techniques and vaccination programs in the 1950s and 1970s,
respectively. It has remained uncertain, however, which of these factors is
causally more responsible for the observed increase in virulence of
circulating viruses. We conducted a phylogenomic study to understand the
evolution of MDV in the context of dramatic changes to poultry farming and
disease control. Our analysis reveals evidence of geographical structuring of
MDV strains, with reconstructions supporting the emergence of virulent viruses
independently in North America and Eurasia. Of note, the emergence of virulent
viruses appears to coincide approximately with the introduction of
comprehensive vaccination on both continents. The time-dated phylogeny also
indicated that MDV has a mean evolutionary rate of ~1.6 × 10−5 substitutions
per site per year. An examination of gene-linked mutations did not identify a
strong association between mutational variation and virulence phenotypes,
indicating that MDV may evolve readily and rapidly under strong selective
pressures and that multiple genotypic pathways may underlie virulence
adaptation in MDV