Pathogen-mediated selection in free-ranging elk populations infected by chronic wasting disease

Authors: MONELLO, RYAN - National Park Service; GALLOWAY, NATHAN - National Park Service; POWERS, JENNY - National Park Service; MADSEN-BOUTERSE, SALLY - Washington State University; EDWARDS, HANK - Wyoming Department Of Game & Fish; WOOD, MARY - Wyoming Department Of Game & Fish; O'Rourke, Katherine; WILD, MARGARET - National Park Service

Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/3/2017
Publication Date: 11/14/2017
Citation: Monello, R.J., Galloway, N.L., Powers, J.G., Madsen-Bouterse, S.A., Edwards, H., Wood, M., O'Rourke, K., Wild, M.A. 2017. Pathogen-mediated selection in free-ranging elk populations infected by chronic wasting disease. Proceedings of the National Academy of Sciences. 114(46):12208-12212. https://doi.org/10.1073/pnas.1707807114.
DOI: https://doi.org/10.1073/pnas.1707807114

Interpretive Summary: Chronic wasting disease (CWD) is a prion disease of free-ranging and captive cervids. This transmissible, fatal brain disease negatively impacts population growth rates of free-ranging deer and elk. Progression of CWD in elk from pre-clinical to clinical disease appears to be associated, at least in part, with an alteration in the prion protein gene. Previous studies using experimental infection of elk with CWD found that disease developed more rapidly when both copies of the prion protein gene allele coded for methionine (M) at codon 132 when compared to leucine (L) (23 months versus 59-63 months post infection, respectively); disease progression was also delayed in elk when both M and L alleles were present (clinical disease observed ~40 months post infection). This study examined frequencies of the M and L alleles in free-ranging elk populations in the presence or absence of CWD. Results indicate an association between increased prevalence of the L allele in elk populations where CWD has been present for at least 30 years. These observations provide a start point from which future studies of free-ranging elk in populations with and without CWD can be used to demonstrate the potential impact of balanced versus directional selection based on prion protein gene alleles.

Technical Abstract: Pathogens can exert a large influence on the evolution of hosts via selection for alleles or genotypes that moderate pathogen virulence. Inconsistent interactions between parasites and the host genome, such as those resulting from genetic linkages and environmental stochasticity, have largely prevented observation of this process in wildlife species. We examined the prion protein gene (PRNP) in North American elk (Cervus elaphus nelsoni) populations that have been infected with chronic wasting disease (CWD), a contagious, fatal prion disease, and compared allele frequency to populations with no history of exposure to CWD. The PRNP in elk is highly conserved and a single polymorphism at codon 132 can markedly extend CWD latency when the minor leucine allele (132L) is present. We determined population exposure to CWD, genotyped 1018 elk from five populations, and developed a hierarchical Bayesian model to examine the relationship between CWD prevalence and PRNP 132L allele frequency. Populations infected with CWD for at least 30-50 years exhibited 132L allele frequencies that were on average twice as great (range = 0.23-0.29) as those from uninfected populations (range = 0.04-0.17). Despite numerous differences between the elk populations in this study, the consistency of increase in 132L allele frequency suggests pathogen-mediated selection has occurred due to CWD. Although prior modeling work predicted that selection will continue, the potential for fitness costs of the 132L allele or new prion protein strains to arise suggest that it is prudent to assume balancing selection may prevent fixation of the 132L allele in populations with CWD.