Biological Resources Division, National Park Service, Fort Collins, CO 80525;
Biological Resources Division, National Park Service, Fort Collins, CO 80525.
Proc Natl Acad Sci U S A. 2017 Nov 14;114(46):12208-12212. doi: 10.1073/pnas.1707807114. Epub 2017 Oct 30.
Pathogens can exert a large influence on the evolution of hosts via selection for alleles or genotypes that moderate pathogen virulence. Inconsistent interactions between parasites and the host genome, such as those resulting from genetic linkages and environmental stochasticity, have largely prevented observation of this process in wildlife species. We examined the prion protein gene () in North American elk () populations that have been infected with chronic wasting disease (CWD), a contagious, fatal prion disease, and compared allele frequency to populations with no history of exposure to CWD. The in elk is highly conserved and a single polymorphism at codon 132 can markedly extend CWD latency when the minor leucine allele (132L) is present. We determined population exposure to CWD, genotyped 1,018 elk from five populations, and developed a hierarchical Bayesian model to examine the relationship between CWD prevalence and 132L allele frequency. Populations infected with CWD for at least 30-50 y exhibited 132L allele frequencies that were on average twice as great (range = 0.23-0.29) as those from uninfected populations (range = 0.04-0.17). Despite numerous differences between the elk populations in this study, the consistency of increase in 132L allele frequency suggests pathogen-mediated selection has occurred due to CWD. Although prior modeling work predicted that selection will continue, the potential for fitness costs of the 132L allele or new prion protein strains to arise suggest that it is prudent to assume balancing selection may prevent fixation of the 132L allele in populations with CWD.
病原体可以通过选择适度病原体毒力的等位基因或基因型对宿主的进化产生巨大影响。寄生虫与宿主基因组之间的相互作用不一致，例如遗传连锁和环境随机性导致的相互作用，在很大程度上阻止了在野生动物物种中观察到这一过程。我们研究了感染慢性消耗性疾病（CWD）的北美的麋鹿种群的朊病毒蛋白基因（），CWD 是一种传染性、致命的朊病毒疾病，并将等位基因频率与没有接触过 CWD 的种群进行了比较。麋鹿中的 高度保守，当存在少数亮氨酸等位基因（132L）时，密码子 132 处的单一多态性可以明显延长 CWD 的潜伏期。我们确定了种群接触 CWD 的情况，对来自五个种群的 1018 头麋鹿进行了基因分型，并开发了一个分层贝叶斯模型来检验 CWD 流行率与 132L 等位基因频率之间的关系。感染 CWD 至少 30-50 年的种群的 132L 等位基因频率平均是未感染种群的两倍（范围为 0.23-0.29）（范围为 0.04-0.17）。尽管本研究中的麋鹿种群存在许多差异，但 132L 等位基因频率增加的一致性表明，由于 CWD，已经发生了病原体介导的选择。尽管先前的建模工作预测选择将继续，但 132L 等位基因或新朊病毒蛋白菌株的适应度成本的出现表明，谨慎假设平衡选择可能会阻止 CWD 种群中 132L 等位基因的固定是明智的。
