Age structuring and spatial heterogeneity in prion protein gene (PRNP) polymorphism in white-tailed deer

Abstract

Chronic-wasting disease (CWD) is a prion-derived fatal neurodegenerative disease that has affected wild cervid populations on a global scale. Susceptibility has been linked unambiguously to several amino acid variants within the prion protein gene (PRNP). Quantifying their distribution across landscapes can provide critical information for agencies attempting to adaptively manage CWD. Here we attempt to further define management implications of PRNP polymorphism by quantifying the contemporary geographic distribution (i.e., phylogeography) of PRNP variants in hunter-harvested white-tailed deer (WTD; Odocoileus virginianus, N = 1433) distributed across Arkansas (USA), including a focal spot for CWD since detection of the disease in February 2016. Of these, PRNP variants associated with the well-characterized 96S non-synonymous substitution showed a significant increase in relative frequency among older CWD-positive cohorts. We interpreted this pattern as reflective of a longer life expectancy for 96S genotypes in a CWDendemic region, suggesting either decreased probabilities of infection or reduced disease progression. Other variants showing statistical signatures of potential increased susceptibility, however, seemingly reflect an artefact of population structure. We also showed marked heterogeneity across the landscape in the prevalence of 'reduced susceptibility' genotypes. This may indicate, in turn, that differences in disease susceptibility among WTD in Arkansas are an innate, populationlevel characteristic that is detectable through phylogeographic analysis.

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)

“…Haplotype A ( f =0.30) and Haplotype B ( f =0.25) reported by Brandt et al (2015, 2018) from northern Illinois were also detected as Haplotype 16 ( f =0.09) and Haplotype 7 ( f =0.05), respectively. The same Haplotype A ( f =0.15) and Haplotype B ( f =0.23) were reported by Chafin et al, 2020 in deer from Arkansas, USA.…”

“…Despite CWD being fatal there is inter-individual variation in susceptibility and clinical progression. Susceptibility and clinical progression are associated with non-synonymous and synonymous genetic variation in the functional prion protein gene (PRNP; Güere et al, 2020; Chafin et al, 2020). Single nucleotide polymorphisms (SNPs) at nucleotide (nt) 60, nt153, nt285, nt286, nt555, and nt676 in deer PRNP have been associated with altered CWD susceptibility or pathogenic processes (Johnson et al, 2006a; Wilson et al, 2009; Brandt et al, 2015; Brandt et al, 2018).…”

“…Single nucleotide polymorphisms (SNPs) at nucleotide (nt) 60, nt153, nt285, nt286, nt555, and nt676 in deer PRNP have been associated with altered CWD susceptibility or pathogenic processes (Johnson et al, 2006a; Wilson et al, 2009; Brandt et al, 2015; Brandt et al, 2018). The presence of CWD appears to affect population PRNP allele frequencies over space and time due to selection (Robinson et al, 2012); however, altered CWD susceptibility and pathogenic processes are clearly polygenic traits (Seabury et al 2020) and disease spread is different in structured populations, which might require different wildlife management practices (Chafin et al, 2020). The efficacy of selection in the face of a novel pressure like CWD is dependent on the effective population size ( N e ).…”

Spatial population genetics in heavily managed species: Separating patterns of historical translocation from contemporary gene flow in white-tailed deer

“…Resource agencies, in particular, should prioritize those populations that retain endemic genetic diversity, and by so doing, tacitly acknowledge the importance of preserving evolutionary legacy (Crandall, Bininda-Emonds, Mace, & Wayne, 2000). Such recognition would capitalize on the many years of natural selection that have operated on those populations prior to anthropogenic interference, which may have generated adaptive genetic variation necessary to withstand changing conditions, or mediated an evolutionary response to disease (e.g., in the PRNP gene; Chafin et al, 2020). This further emphasizes the importance of integrating genomic methods for heavily managed species (Flanagan et al, 2017), given their recognized lack of intraspecific adaptive variation [i.e., a 'Darwinian shortfall' in biodiversity conservation (Diniz-Filho, Loyola, Raia, Mooers, & Bini, 2013)].…”

“…Although dense spatial and genomic sampling may offer a composite resolution (e.g., Chafin et al, 2020;Linck et al, 2019), it does not necessarily supplant other approaches. For example, sampling density was shown herein to be a particular limiting factor in geolocation analyses, with high prediction error in regions of the state sparsely sampled (Fig.…”