Polymorphisms of the <i>prion protein</i> gene (<i>PRNP </i>) in Alaskan moose (<i>Alces alces gigas</i>)

Source/description: The prion protein (PRNP) gene of mammals encodes a prion protein (PrP), which is expressed in many tissues including the brain. Misfolded PrP conformers are responsible for neurodegenerative diseases known as spongiform encephalopathies. Transmissible spongiform encephalopathies (TSEs) include bovine spongiform encephalopathy, ovine scrapie, human Creuzfeldt–Jakob disease and chronic wasting disease (CWD)1,2 in mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus) and Rocky Mountain elk (Cervus elaphus). First found in Colorado, CWD has now been identified in the eastern USA, as far south as New Mexico and as far north as west-central Canada.3 Polymorphisms of PRNP appear to be linked to susceptibility to TSE in numerous species including free-ranging white-tailed deer4 and mule deer.5 In mule deer, the SS genotype at residue 225 is associated with a higher incidence of CWD.5 Differences in PrP amino acid sequence are believed to be species barriers to disease transmission.6 However, Wyoming moose sequences that were previously deposited in GenBank (AY225484 and AY225485) are similar to the sequence of Odocoileus. CWD has not been observed in Rocky Mountain moose (Alces alces shirasi) or in caribou at higher latitudes (Rangifer tarandus), yet both species overlap the geographical range of Odocoileus species. We report here the PRNP sequences for 44 Alaskan moose (Alces alces gigas). Polymerase chain reaction conditions and sequence analysis: Genomic DNA was purified from blood samples of 44 moose (Alces alces gigas) that were sampled from eight locations across Alaska. DNA purification protocols, primers, amplification conditions and sequence analysis methods are provided in Appendix S1. Polymorphisms: Two unique sequences (i.e. alleles) were found in the sequences of 44 individual moose (DQ154297 and DQ154298); these differed only at codon 209. The allele encoding methionine was present with a frequency of 0.45, and the allele encoding isoleucine was present with a frequency of 0.55. The diploid genotypes did not depart significantly from Hardy–Weinberg predictions (χ2 = 0.4, P < 0.01). Comments: The conservation of amino acid sequences in the PrP of moose, caribou and deer is striking (Table 1) and consistent with the fact that all three genera are in the subfamily Capreolinae. In comparison with caribou, Alaskan moose samples show six synonymous substitutions (bases 195, 231, 324, 360, 384 and 674), presumably reflecting purifying selection for the unique conformation of the globular N-terminal domain of cervid prions.7 CWD has been transmitted to moose by an oral route in an experimental laboratory setting.8 Genetic similarities, susceptibility in the laboratory setting and overlapping geographical ranges suggest the lack of a barrier to the transmission of prion disease from mule and white-tailed deer to moose. The absence of reports of CWD transmission to moose in natural settings may reflect ecological or epidemiological factors. Moose tend to be more solitary than deer of the genus Odocoileus, and dense social aggregations might be prerequisites of CWD epizootic outbreaks in cervids. Acknowledgements: This work was supported by grants from the National Institutes of Health (NCRR – 2 P20 RR016466) and the National Science Foundation (0346770). The moose samples were from the Alaska Frozen Tissue Collection of the University of Alaska Museum, which was funded in part by grants from the National Science Foundation. Appendix S1 Table of differences among prion alleles, Materials and Methods. Figure S1 Locations of sites where moose were sampled in Alaska. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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