Pathogens can cause host extinction, affect population dynamics, and influence natural selection. Host susceptibility to pathogens can vary by species, demographics, and genetics which affect epizootic dynamics; ultimately determining population trends and evolution. Chronic wasting disease (CWD), a fatal neuro-degenerative prion disease of cervids, has varying host susceptibility conferred by polymorphisms of the prion protein gene (PRNP) at the 96 codon for white-tailed deer (Odocoileus virginianus). Deer with the homozygous Glycine allele (96GG) are most susceptible and a single Serine allele (96GS/96SS) reduces the risk of infection and mortality. We developed epizootiological models that demonstrate CWD infection and disease-associated mortality were higher for the more susceptible (96GG) genotype; and, infection was higher for males than females. We used population models to evaluate future shifts in genotype frequencies under alternative harvest and infection rate scenarios. Genetic shifts towards less susceptible genotypes were predicted as CWD prevalence increased during the course of an outbreak. This further increased CWD prevalence, and likely environmental contamination from prion shedding, due to longer incubation periods. Alternative harvest management strategies directly influenced CWD prevalence and spread, the rate of genetic selection, and deer population growth. 

Synthesis and applications: We show that CWD transmission varied by sex, age classes, and genotypes, and that CWD disease-associated mortality varied by genotype. Together, these forces lead to CWD-mediated genetic selection for a white-tailed deer population. We predict that genetic selection pressure increases when hunter harvest pressure is lowered, and conversely, increasing hunter harvest can reduce genetic selection rates of antlered deer. Our results support the control of CWD prevalence by aggressive harvest of adult males because they have the highest infection rates. Our results have strong implications for evolution, disease ecology, geographic spread, disease mitigation, and cervid population management.