Emerging prion disease drives host selection in a wildlife population

Abstract

Infectious diseases are increasingly recognized as an important force driving population dynamics, conservation biology, and natural selection in wildlife populations. Infectious agents have been implicated in the decline of small or endangered populations and may act to constrain population size, distribution, growth rates, or migration patterns. Further, diseases may provide selective pressures that shape the genetic diversity of populations or species. Thus, understanding disease dynamics and selective pressures from pathogens is crucial to understanding population processes, managing wildlife diseases, and conserving biological diversity. There is ample evidence that variation in the prion protein gene (PRNP) impacts host susceptibility to prion diseases. Still, little is known about how genetic differences might influence natural selection within wildlife populations. Here we link genetic variation with differential susceptibility of white-tailed deer to chronic wasting disease (CWD), with implications for fitness and disease-driven genetic selection. We developed a single nucleotide polymorphism (SNP) assay to efficiently genotype deer at the locus of interest (in the 96th codon of the PRNP gene). Then, using a Bayesian modeling approach, we found that the more susceptible genotype had over four times greater risk of CWD infection; and, once infected, deer with the resistant genotype survived 49% longer (8.25 more months). We used these epidemiological parameters in a multi-stage population matrix model to evaluate relative fitness based on genotype-specific population growth rates. The differences in disease infection and mortality rates allowed genetically resistant deer to achieve higher population growth and obtain a long-term fitness advantage, which translated into a selection coefficient of over 1% favoring the CWD-resistant genotype. This selective pressure suggests that the resistant allele could become dominant in the population within an evolutionarily short time frame. Our work provides a rare example of a quantifiable disease-driven selection process in a wildlife population, demonstrating the potential for infectious diseases to alter host populations. This will have direct bearing on the epidemiology, dynamics, and future trends in CWD transmission and spread. Understanding genotype-specific epidemiology will improve predictive models and inform management strategies for CWD-affected cervid populations.

Chronic wasting disease model of genetic selection favoring prolonged survival in Rocky Mountain elk (Cervus elaphus)

“…The slow progression of disease associated with CWD infection may not exert enough selective pressure to cause a dramatic genotypic shift similar to the one presented in our model. However, as demonstrated by Robinson et al (2012), if the timescale is drawn out to several hundred years, progression of CWD likely will cause a switch to higher frequencies of slower disease progression genotypes in wild populations.…”

“…Secondly, there is an elk methionine/ leucine (M/L) polymorphism at PrP C codon 132 that restricts propagation of PrP CWD resulting in a prolonged incubation time (O'Rourke et al 1999, Hamir et al 2006, O'Rourke et al 2007, Green et al 2008. A prolonged incubation time could allow for an extended reproductive life, and induce population-level increases in frequency of the associated allele similar to those predicted by Robinson et al (2012) in white-tailed deer.…”

The ecology of environmental DNA and implications for conservation genetics

“…The first path is immediately accessible to studies using genomic model organisms and sampling designs with predictable and robust differences in genome function (e.g., Robinson et al 2012). This path will expand to conservation as genomic resources develop for threatened and invasive species (Shafer et al 2015).…”

Genomics and the challenging translation into conservation practice

“…Even if detected, the overall impact of individual loci on conservation and management will still remain tangential (e.g., through population models and projections [54]) 150 until genotype-phenotype correlations of the focal species can be inferred with a high degree of certainty.…”

“…As the proportion of gene sequences with functional annotations grows, the value of individual loci will increase for conservation (e.g., detecting disease susceptibility [54]), and it is conceivable that loci of known function could be managed and propagated under 140 certain conservation scenarios (e.g., disease outbreak in a small population -see also Box 2). Functional annotation can be borrowed from related species [55] and databases (e.g., Gene Ontology Consortium) under the assumption of orthology, though with unclear implications for the organism in question [56].…”