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.

摘要

慢性消耗性疾病 (CWD) 是一种朊病毒衍生的致命神经退行性疾病，已在全球范围内影响了野生鹿科动物种群。易感性与朊病毒蛋白基因 ( PRNP ) 中的几种氨基酸变体明确相关。量化它们在景观中的分布可以为试图自适应管理 CWD 的机构提供关键信息。在这里，我们试图通过量化猎人收获的白尾鹿（WTD；Odocoileus virginianus）中PRNP变体的当代地理分布（即系统地理学）来进一步定义PRNP多态性的管理含义, N = 1433) 分布在阿肯色州（美国），包括自 2016 年 2 月发现该疾病以来 CWD 的一个焦点。其中，PRNP与充分表征的 96S 非同义替换相关的变异显示，在较老的 CWD 阳性队列中，相对频率显着增加。我们将这种模式解释为 CWD 流行地区 96S 基因型的预期寿命更长，这表明感染概率降低或疾病进展减少。然而，其他显示出潜在易感性增加的统计特征的变体似乎反映了人口结构的人工制品。我们还在“降低易感性”基因型的流行中显示了整个景观的显着异质性。这反过来可能表明，阿肯色州 WTD 之间疾病易感性的差异是一种先天的、人口水平的特征，可通过系统地理学分析检测到。