Abstract:PRNP genotypes, number of octarepeats (PHGGGWGQ) and indels in the PRNP promoter can influence the progression of prion disease in mammals. We found no relationship between presence of promoter indels in white-tailed deer and mule deer from Nebraska and CWD presence. White-tailed deer with the 95 H allele and G20D mule deer were more likely to be CWDfree, but unlike other studies white-tailed deer with the 96S allele(s) were equally likely to be CWD-free. We provide the first information on PRNP genotypes and … Show more
“…To date, nucleotide variants were observed in mule deer at 5 positions; 2 synonymous substitutions at aa positions 131, 247 and 3 non-synonymous substitutions at aa positions D20G, S225F, Q226K [97,104,105]. Of note, only two heterozygous animals at codon 226 were identified in Nebraska mule deer (N = 122), suggesting a low percentage of animals carrying the 226 K allele.…”
Section: Odocoileus Hemionus or Mule Deermentioning
To date, chronic wasting disease (CWD) is the most infectious form of prion disease affecting several captive, free ranging and wild cervid species. Responsible for marked population declines in North America, its geographical spread is now becoming a major concern in Europe. Polymorphisms in the prion protein gene (PRNP) are an important factor influencing the susceptibility to prions and their rate of propagation. All reported cervid PRNP genotypes are affected by CWD. However, in each species, some polymorphisms are associated with lower attack rates and slower progression of the disease. This has potential consequences in terms of genetic selection, CWD diffusion and strain evolution. CWD also presents a zoonotic risk due to prions capacity to cross species barriers. This review summarizes our current understanding of CWD control, focusing on PRNP genetic, strain diversity and capacity to infect other animal species, including humans.
“…To date, nucleotide variants were observed in mule deer at 5 positions; 2 synonymous substitutions at aa positions 131, 247 and 3 non-synonymous substitutions at aa positions D20G, S225F, Q226K [97,104,105]. Of note, only two heterozygous animals at codon 226 were identified in Nebraska mule deer (N = 122), suggesting a low percentage of animals carrying the 226 K allele.…”
Section: Odocoileus Hemionus or Mule Deermentioning
To date, chronic wasting disease (CWD) is the most infectious form of prion disease affecting several captive, free ranging and wild cervid species. Responsible for marked population declines in North America, its geographical spread is now becoming a major concern in Europe. Polymorphisms in the prion protein gene (PRNP) are an important factor influencing the susceptibility to prions and their rate of propagation. All reported cervid PRNP genotypes are affected by CWD. However, in each species, some polymorphisms are associated with lower attack rates and slower progression of the disease. This has potential consequences in terms of genetic selection, CWD diffusion and strain evolution. CWD also presents a zoonotic risk due to prions capacity to cross species barriers. This review summarizes our current understanding of CWD control, focusing on PRNP genetic, strain diversity and capacity to infect other animal species, including humans.
“…A later study documented a 10% increase in the slow 225F allele frequency in less than 10 years [ 19 ], although this study focused on a single mule deer herd and, therefore, the change in genotype frequency could potentially be due to genetic drift, rather than selection. Other studies have found a correlation between CWD status and PRNP codon 20 genotype in mule deer in western Canada and Nebraska, USA [ 31 , 32 ]; however, clinical evidence for differential disease progression related to codon 20 does not yet exist. These studies found that at codon 20, mule deer with two copies of the common amino acid aspartic acid (D; nucleotide sequence GAC) were less likely to test positive for CWD than deer with at least one copy of the variant amino acid glycine (G; nucleotide sequence GGC).…”
Infectious diseases play an important role in wildlife population dynamics by altering individual fitness, but detecting disease-driven natural selection in free-ranging populations is difficult due to complex disease–host relationships. Chronic wasting disease (CWD) is a fatal infectious prion disease in cervids for which mutations in a single gene have been mechanistically linked to disease outcomes, providing a rare opportunity to study disease-driven selection in wildlife. In Wyoming, USA, CWD has gradually spread across mule deer (
Odocoileus hemionus
) populations, producing natural variation in disease history to evaluate selection pressure. We used spatial variation and a novel temporal comparison to investigate the relationship between CWD and a mutation at codon 225 of the mule deer prion protein gene that slows disease progression. We found that individuals with the ‘slow’ 225F allele were less likely to test positive for CWD, and the 225F allele was more common in herds exposed to CWD longer. We also found that in the past 2 decades, the 225F allele frequency increased more in herds with higher CWD prevalence. This study expanded on previous research by analysing spatio-temporal patterns of individual and herd-based disease data to present multiple lines of evidence for disease-driven selection in free-ranging wildlife.
“…Although relatively conserved, the (diploid) PRNP gene in animals includes many alleles, differing by as few as one base pair up to many. For example, in a sample of 214 white-tailed deer from Nebraska, 10 alleles at the PRNP gene (771 bp) were observed, differing by from 1 to 3 bp ( Zink et al., 2020 ). When these sequences were translated to amino acids (n = 257), there were seven variable sites that defined eight distinct amino acid sequences.…”
Section: Exploring Prnp Phylogeny and Cwd In White-tailed Deermentioning
confidence: 99%
“…Genbank numbers given in original publication ( Vázquez-Miranda and Zink, 2020 ; Zink et al, 2020 ). Figure 2 Condensed tree derived from amino acid sequences from 214 white-tailed deer from Nebraska ( Zink et al., 2020 ) at the PRNP locus showing CWD status. Labels on branches are the genotypes at positions 95 or 96; if not shown, then the wild type is present.…”
Section: Exploring Prnp Phylogeny and Cwd In White-tailed Deermentioning
confidence: 99%
“…Each deer except for the two black-tailed deer from Alaska (AK) have different nucleotide sequences. Genbank numbers given in original publication ( Vázquez-Miranda and Zink, 2020 ; Zink et al, 2020 ).…”
Section: Exploring Prnp Phylogeny and Cwd In White-tailed Deermentioning
Evolutionary biologists and disease biologists use the terms strain and adaptation in Chronic Wasting Disease (CWD) research in different ways. In evolutionary biology, a strain is a nascent genetic lineage that can be described by a genealogy, and a phylogenetic nomenclature constructed to reflect that genealogy. Prion strains are described as showing distinct host range, clinical presentation, disease progression, and neuropathological and PrP biochemical profiles, and lack information that would permit phylogenetic reconstruction of their history. Prion strains are alternative protein conformations, sometimes derived from the same genotype. I suggest referring to prion strains as ecotypes, because the variant phenotypic conformations (“strains”) are a function of the interaction between PRNP amino acid genotype and the host environment. In the case of CWD, a prion ecotype in white-tailed deer would be described by its genotype and the host in which it occurs, such as the H95 + ecotype. However, an evolutionary nomenclature is difficult because not all individuals with the same PRNP genotype show signs of CWD, therefore creating a nomenclature reflecting and one-to-one relationship between PRNP genealogy and CWD presence is difficult. Furthermore, very little information exists on the phylogenetic distribution of CWD ecotypes in wild deer populations. Adaptation has a clear meaning in evolutionary biology, the differential survival and reproduction of individual genotypes. If a new prion ecotype arises in a particular host and kills more hosts or kills at an earlier age, it is the antithesis of the evolutionary definition of adaptation. However, prion strains might be transmitted across generations epigenetically, but whether this represents adaptation depends on the fitness consequences of the strain. Protein phenotypes of PRNP that cause transmissible spongiform encephalopathies (TSEs), and CWD, are maladaptive and would not be propagated genetically or epigenetically via a process consistent with an evolutionary view of adaptation. I suggest terming the process of prion strain origination “phenotypic transformation”, and only adaptation if evidence shows they are not maladaptive and persist over evolutionary time periods (e.g., thousands of generations) and across distinct species boundaries (via inheritance). Thus, prion biologists use strain and adaptation, historically evolutionary terms, in quite different ways.
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