Rapid adaptation to a globally introduced virulent pathogen in a keystone species.

Emerging infectious diseases are one of the foremost contemporary threats to biodiversity conservation. Outbreaks of novel pathogens can lead to the extinction of host populations, loss of gene flow due to extirpation, and bottlenecks in host populations with surviving individuals. In outbreaks with survivors, pathogens can exert strong selection on hosts, in some cases leading to the evolution of resistance or tolerance in the host population. The pathogen causing sylvatic plague, , was introduced to North America in the early 1900s and caused widespread population declines in prairie dogs (genus ), which experience >95% mortality during epizootics. Recently, survival from plague was documented in a small number of black-tailed prairie dogs () in natural populations in Colorado (United States). We performed whole-genome sequencing on all seven individuals that survived infection with plague and seven individuals that likely died. Using genome-wide association tests, outlier tests, and other inferences of selection, we detected single nucleotide polymorphisms (SNPs) on five scaffolds that were strongly associated with survivorship from plague in nature. One candidate gene, inducible T-cell stimulator (), was also associated with survival in humans during the Black Death in London (United Kingdom), suggesting conservation of gene function across taxonomically diverse lineages. In addition, three candidate genes (, , and ) are different from but in the same gene classes (transmembrane proteins, protocadherins, and Kasuza protein-binding genes) as candidate genes for plague resistance in great gerbils, providing support for the hypothesis that parallel evolution may occur at the level of gene classes in addition to individual genes. Understanding the genomic basis of immunity can enable genetically informed management actions, such as targeted relocation to protect grassland species. Moreover, understanding how rapid adaptation to pathogens occurs can help us predict the time frame and spatial scale at which adaptation may occur, during which other interventions are needed.