Capsid gene divergence in rabbit hemorrhagic disease virus

The emergence and rapid global spread of rabbit hemorrhagic disease virus (RHDV) remains enigmatic despite two decades of study, largely due to the difficulties associated with modelling substitution processes of the RNA genome for phylogenetic inference. We used maximum-likelihood and Bayesian methods to investigate rates of molecular evolution in the capsid gene, finding evidence of positive selection and of variable substitution rates between nucleotide sites and between lineages. The maximum-likelihood and Bayesian analyses produced fully congruent topologies; however, strong support for older nodes of the phylogeny was only obtained from the Bayesian analyses that utilized the additional information of collection dates for RHDV isolates spanning 22 years. These dates also allowed calibration of the RHDV phylogenetic tree in a calendar year timescale and estimation of dates for the most recent common ancestors of virulent and benign strains. These dates suggested the divergence of RHDV approximately 20 years prior to the first report of haemorrhagic disease in rabbits.