Schwensow Nina, Pederson Stephen, Peacock David, Cooke Brian, Cassey Phillip
Institute of Evolutionary Ecology and Conservation Genomics, University of Ulm, Ulm, Germany.
Centre for Applied Conservation Science, and School of Biological Sciences, University of Adelaide, SA, Australia.
Mol Ecol. 2020 Oct;29(19):3777-3794. doi: 10.1111/mec.15498. Epub 2020 Jun 20.
Since its introduction to control overabundant invasive European 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 close to genes potentially important for increased RHD resistance. The identified genes are known to be involved in virus infections and immune reactions or had previously been identified as being differentially expressed in healthy versus 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 data set 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 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.
自从引入高致病性兔出血症病毒（RHDV）来控制数量过多的入侵欧洲兔（穴兔）以来，这种病毒每年都会在澳大利亚兔群中引发定期的疾病爆发。虽然最初在整个大陆范围内使兔子数量减少了60%，但实验证据表明，经历了RHDV驱动选择的野兔的遗传抗性有所增强。为了确定能够解释对这种生物防治病毒抗性增强的遗传适应性，我们调查了南澳大利亚一个兔群的全基因组单核苷酸多态性（SNP）等位基因频率变化，该兔群于1996年（RHDV出现之前）采样，在经历了16年的RHDV疫情爆发后再次采样。我们在可能对增强RHD抗性至关重要的基因内部或附近，鉴定出了几个等位基因频率发生变化的SNP。已确定这些基因与病毒感染和免疫反应有关，或者之前已被鉴定为在健康兔与急性感染RHDV的兔中差异表达。此外，我们在一项模拟研究中表明，等位基因/基因型频率的变化不能仅用遗传漂变来解释，并且在另一个澳大利亚兔群中，几个候选基因也被鉴定为与RHD存活相关。我们独特的数据集使我们能够鉴定出在自然条件下进化而来的、在实验环境中不可能实现的时间跨度内对RHDV具有抗性的候选基因。此外，它提供了一个罕见的宿主遗传适应病毒驱动选择以应对突然出现的传染病的例子。
