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 CWD-endemic 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, population-level characteristic that is detectable through phylogeographic analysis.

Keywords: Adaptive management; chronic-wasting disease; demography; disease susceptibility; haplotype; selection; white-tailed deer.

Figure 1.

Sampling locations for white-tailed deer tissues from Arkansas evaluated in this study. The red shaded area indicates the 16 counties included in the 2019 Chronic Wasting Disease Management Zone (CWDMZ), with a yellow boundary surrounding a focal area encompassing Newton County. Black dots represent collection localities for each individual tissue. Note that the boundaries of the CWDMZ have since expanded

Figure 2.

Haplotype network showing relationship of prion gene variants (PRNP) detected across 1,433 white-tailed deer collected from 75 counties in Arkansas (2016–2019). Data are based on sequence analysis of 720 nucleotides. Circles represent 20 haplotypes (=alleles) with size reflecting frequency of occurrence in entire data set (Table 2), and tick marks representing number of mutations (=nucleotide substitutions) distinguishing one from another (Table 1). Colour codes reflect relative frequency among CWD-positive (red) and CWD-negative/undetected (green). Letters correspond to haplotype names (per Brandt et al. 2015), with haplotypes unique to Arkansas indicated with numbers (AR#). Haplotypes sharing the 96S mutation are indicated with (*)

Figure 3.

Stacked histogram of 2,866 PRNP haplotypes detected in white-tailed deer collected in Arkansas, 2016–2019. Haplotypes were determined by phasing individual genotypes derived from sequencing 1,433 deer across 720 bp of the PRNP gene. Letters (A through V) refer to haplotypes identified in Brandt et al. (2015), whereas numbers (1–4) are haplotypes unique to Arkansas, and thus previously unreported. Frequencies are plotted for all 1,433 samples (=statewide) as well as for a subset of 314 samples from Newton County (N = 628 chromosomes). Colour codes reflect frequency among CWD-positive (CWD+) and CWD-negative (CWD-) samples; unknown indicates samples that were not tested for CWD. For each haplotype, paired bars report values statewide (left) and for the Newton County subset (right)

Figure 4.

Topographies that represent interpolated haplotype frequencies for the PRNP gene in Arkansas. Frequency is depicted by colour, with blue reflecting low occurrence (0–5%) whereas red indicating 46–50+% of haplotypes were of this type

Figure 5.

Relative frequency and odds ratio for two haplotypes of the prion gene PRNP haplotypes detected in white-tailed deer age cohorts (<1 year to 5+ years) sampled in Arkansas from 2016–2019. Prion gene variant Haplotype C (top panel) has been associated with reduced susceptibility to CWD, whereas Haplotype B (lower panel) has been associated with higher susceptibility (Brandt et al. 2018). Data are based on phased haplotypes derived from 720 nucleotides of the PRNP gene sequenced across 1,433 deer