Characterizing the demographic history and prion protein variation to infer susceptibility to chronic wasting disease in a naïve population of white-tailed deer (Odocoileus virginianus)

Abstract

Assessments of the adaptive potential in natural populations are essential for understanding and predicting responses to environmental stressors like climate change and infectious disease. Species face a range of stressors in human-dominated landscapes, often with contrasting effects. White-tailed deer (deer) are expanding in the northern part of their range following decreasing winter severity and increasing forage availability. Chronic wasting disease (CWD), a prion disease affecting cervids, is likewise expanding and represents a major threat to deer and other cervids. We obtained tissue samples from free-ranging deer across their native range in Ontario, Canada which has yet to detect CWD in wild populations of cervids. We used high-throughput sequencing to assess neutral genomic variation, and variation in the PRNP gene that is partly responsible for the protein misfolding when deer contract CWD. Neutral variation revealed a high number of rare alleles and no population structure, and demographic models suggested a rapid historical population expansion. Allele frequencies of PRNP variants associated with CWD susceptibility and disease progression were evenly distributed across the landscape and consistent with deer populations not infected with CWD. We then estimated the selection coefficient of CWD, with simulations showing an observable and rapid shift in PRNP allele frequencies that coincides with the start of a novel CWD epidemic. Sustained surveillance of genomic and PRNP variation can be a useful tool for CWD-free regions where deer are managed for ecological and economic benefits.

Pathogen‐mediated selection and management implications for white‐tailed deer exposed to chronic wasting disease

“…It is often difficult to identify which host genetic components are directly impacted by pathogen selection and to quantify the potential rate of population adaptation to pathogen pressures (Dwyer et al, 1990;McKnight et al, 2017). However, increasing application of genomic technology has enhanced research on pathogen-driven selection (Blanchong et al, 2016;Cornetti & Tschirren, 2020;Haworth et al, 2021). Moreover, epizootiological characteristics such as transmission dynamics, disease-associated mortality and rate of spread can influence the selective forces acting upon free-ranging populations (Altizer, Harvell, et al, 2003).…”

“…Heterogeneous transmission dynamics resulting from differences in social behaviour, contact rates and host demographics (Altizer, Nunn, et al, 2003;Cross et al, 2009;Grear et al, 2010) makes it complicated to understand the interacting factors that drive epizootics and affect host genetic selection (Dobson, 2004;Kardos & Shafer, 2018;VanderWaal et al, 2014). As a result, few studies have measured the strength of selection pressure and rates of host genetic evolution in wildlife populations (Altizer, Nunn, et al, 2003;Haworth et al, 2021;.…”

Estimating sequence diversity of prion protein gene (PRNP) in Portuguese populations of two cervid species: red deer and fallow deer

“…Although the origin of CWD is not well known, the fatality, clinical progression and susceptibility/resistance of CWD has been linked to the genetic variation in functional prion protein gene PRNP [14][15][16]. In cervids the PRNP is highly conserved, however, several preprint (which was not certified by peer review) is the author/funder.…”

“…The copyright holder for this this version posted August 17, 2022. ; https://doi.org/10.1101/2022.08. 16.504133 doi: bioRxiv preprint sequence variations of PRNP have been identified and characterized as being implicated in prion disease susceptibility/resistance as well as in CWD disease progression [16,17].…”

“…The studies with more impact in cervid PRNP genetics have been made in USA and Canada, where both natural and experimental infection of deer species has allowed for the identification of PRNP sequence variations that are associated with reduced incidence of disease and/or slower disease progression. Since the identification of the first PRNP variation in codon 132 (M132L) in wapiti deer suggesting a reduced susceptibility to infection when the 132L variant is present, several other PRNP mutations in other cervids have been associated with CWD susceptibility: Q95H, G96S and A116G (white-tailed deer), S225F (mule deer) [16].…”