Collaborative Research: EDGE CMT: Predicting the evolution of disease resistance across heterogeneous landscapes

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Wildlife infectious diseases can cause extinctions and populations declines in animals, often also impacting public health. Sylvatic (better known as bubonic) plague was introduced to North America in 1900 and is now maintained in native mammals in the western U.S., periodically eliciting disease outbreaks. Although some species seem to have natural resistance, others—such as prairie dogs—are highly susceptible. Despite the detection of plague resistance in a small number of prairie dogs, the disease still decimates populations throughout their range. The continued susceptibility of prairie dogs suggests there is some constraint inhibiting the widespread evolution of resistance to plague. This project uses whole-genome and transcriptome sequencing of resistant and susceptible prairie dogs to determine the genomic basis of recently evolved plague resistance. Mutations associated with resistance in natural populations and experiments will then be mapped in nature to determine the spatial distribution of resistance alleles and predict the location of potential resistance hotspots. Museum specimens of prairie dogs will also be genotyped to determine the rate of evolution of plague resistance. Given the increasing rate of novel pathogens emerging around the globe, this research will have broad implications for understanding when and where adaptation in naïve hosts is likely to persist. This project will use research to enhance education by building capacity in universities serving Native American and Hispanic students. Traveling genomics workshops will be delivered to students and faculty, and students will be mentored at their own institutions as they conduct independent research in the system.Adaptation to pathogens should be heavily favored by selection: Once immunity evolves, it should sweep to fixation across a species’ range. Paradoxically, a more commonly observed pattern is variable immunity. Because there are multiple explanations for incomplete resistance, the ecological and evolutionary conditions under which resistance to novel pathogens is maintained are still poorly understood. For instance, to what extent does the habitat matrix influence the maintenance of resistance through processes such as gene dilution? Does the de novo evolution of resistance independently across populations lead to epistatic interactions preventing widespread resistance? Resistance to sylvatic plague (caused by the bacterium Yersinia pestis) has been observed in prairie dogs (genus Cynomys) in six western states, but resistance is still rare. This project integrates genomic and transcriptomic analysis of experimentally infected animals with rangewide spatiotemporal sampling to elucidate how, when and where resistance evolves, and what prevents this adaptive trait from sweeping to fixation. Previous experimental infections and a natural epizootic will be used to determine the genomic basis of resistance in two species. Alleles associated with resistance, along with neutral alleles serving as a null model, will be genotyped in latitudinal transects spanning populations with different plague introduction times, and in museum specimens from at least three distinct time ranges. These data will enable estimates of the rate of evolution of resistance alleles and inferences of the landscape spatial structure and genomic characteristics facilitating resistance. Understanding how adaptation persists across space and time can enable facilitated adaptation in imperiled systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.