Comparative Phylodynamics of Rabbit Hemorrhagic Disease Virus in

The introduction of rabbit hemorrhagic disease virus (RHDV) into Australia and New Zealand during the 1990s as a means of controlling feral rabbits is an important case study in viral emergence. Both epidemics are exceptional in that the founder vi-ruses share an origin and the timing of their release is known, providing a unique opportunity to compare the evolution of a sin-gle virus in distinct naive populations. We examined the evolution and spread of RHDV in Australia and New Zealand through a genome-wide evolutionary analysis, including data from 28 newly sequenced RHDV field isolates. Following the release of the Australian inoculum strain into New Zealand, no subsequent mixing of the populations occurred, with viruses from both coun-tries forming distinct groups. Strikingly, the rate of evolution in the capsid gene was higher in the Australian viruses than in those fromNew Zealand, most likely due to the presence of transient deleterious mutations in the former. However, estimates of both substitution rates and population dynamics were strongly sample dependent, such that small changes in sample composi-tion had an important impact on evolutionary parameters. Phylogeographic analysis revealed a clear spatial structure in the Australian RHDV strains, with a major division between those viruses fromwestern and eastern states. Importantly, RHDV se-quences from the state where the virus was first released, South Australia, had the greatest diversity and were diffuse throughout both geographic lineages, such that this region was likely a source population for the subsequent spread of the virus across th