Spatial and Temporal Patterns of Prion Gene Variation Are Consistent With a Response to Chronic Wasting...

Chronic wasting disease (CWD) poses a threat to cervids and is increasingly prevalent throughout North America. Prion protein gene (PRNP) variation may confer some degree of genetic resilience, creating an impetus to examine changes in allelic variation and to assess signatures of selection. We investigated the association between CWD and PRNP variation in white-tailed deer (WTD) (Odocoileus virginianus) and mule deer (MD) (Odocoileus hemionus) sampled in Alberta, Canada between 2014 and 2017. We sequenced the PRNP gene of 575 WTD (67 CWD-positives) and 660 MD (202 CWD-positives) and detected 14 single nucleotide polymorphic loci in WTD and 8 in MD. No association was identified between the MD genetic variation and disease status. Notably, a variant at 286 was detected in WTD, resulting in an amino acid change at codon 96 (G96S). Genotype counts at this locus were significantly associated with CWD status, with the 96S allele under-represented among CWD-positive and over-represented among negative individuals. For a CWD-positive individual, the odds of being homozygous for the major allele (G96/G96) were more than sevenfold greater than being homozygous for the minor allele (96S/96S). Following additional sequencing of 1612 WTD, we examined spatial and temporal variability of this locus in association with the disease history on the landscape. Among females, the frequency of 96S varied negatively with the distance to where CWD was first detected. Additionally, the 96S allele frequency has increased over time, in line with expectations based on estimated disease selection coefficients. Our results are consistent with CWD selection pressure resulting in increasing frequency of the 96S allele in space and time, indicating it may confer some resilience and extended infection with CWD.