Adaptive changes in the genomes of wild rabbits after 16 years of viral epidemics

Since its introduction to control overabundant alien rabbits (Oryctolagus
cuniculus), the highly virulent Rabbit Haemorrhagic Disease Virus (RHDV)
has caused regular annual disease outbreaks in Australian rabbit
populations. Although initially reducing rabbit abundance by 60%,
continent-wide, experimental evidence has since indicated increased
genetic resistance in wild rabbits that have experienced RHDV-driven
selection. To identify genetic adaptations, which explain the increased
resistance to this biocontrol virus, we investigated genome-wide SNP
(single nucleotide polymorphism) allele frequency changes in a South
Australian rabbit population that was sampled in 1996 (pre-RHD genomes)
and after 16 years of RHDV outbreaks. We identified several SNPs with
changed allele frequencies within or in proximity of genes that have roles
potentially important for increased RHD resistance. Many of the identified
genes are known to be involved in virus infections or immunity, or had
previously been identified as being  differentially expressed in
healthy vs. acutely RHDV-infected rabbits. Furthermore, we show in a
simulation study that the allele/genotype frequency changes cannot be
explained by drift alone, and that several candidate genes had also been
identified as being associated with surviving RHD in a different
Australian rabbit population. Our unique dataset allowed us to identify
candidate genes for RHDV resistance that have evolved under natural
conditions, and over a time span that would not have been feasible to
study in an experimental setting. Moreover, it provides a rare example of
host genetic adaptations to virus-driven selection in response to a
suddenly emerging infectious disease.