Variation in the PRNP gene of Pere David’s deer (Elaphurus davidianus) may impact genetic vulnerability to chronic wasting disease

Abstract

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy caused by prions that has spread across cervid species in North America since the 1960s and has recently been detected in Eurasian cervids. The Association of Zoos and Aquariums (AZA) considers CWD to be of major concern for cervids in AZA-accredited facilities because of the indirect transmission risk of the disease and the impact of CWD regulatory protocols on captive breeding programs. Vulnerability to CWD is affected by variation in the PRNP gene that encodes the prion protein. We therefore sequenced PRNP in Pere David’s deer (Elaphurus davidianus), a species that was extinct in the wild for more than a century and descends from ca. 11 founders. In 27 individuals, we detected two PRNP haplotypes, designated Elad1 (51 of 54 sequences) and Elad2 (3 of 54 sequences). The two haplotypes are separated by four single nucleotide polymorphisms (SNPs), three of which are non-synonymous. Both Elad1 and Elad2 have polymorphisms that in other cervid taxa are associated with reduced vulnerability to CWD. The two haplotypes are more similar in sequence to PRNP in other cervids than to each other. This suggests that PRNP in cervids may have been under long-term balancing selection, as has been shown for PRNP in non-cervid taxa, and which could account for the presence of multiple haplotypes among founders. There may be a fitness benefit in maintaining both PRNP haplotypes in the species because variation in the prion protein amino acid sequence can limit transmission of CWD.