Collaborative Research: EDGE CMT: Predicting the evolution of disease resistance across heterogeneous landscapes

合作研究：EDGE CMT：预测异质景观中抗病性的演变

• 批准号: 2220815
• 负责人: Loren Cassin Sackett
• 金额: $ 103.06万
• 依托单位: University of Louisiana at Lafayette
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2220815&HistoricalAwards=false
• 关键词: Collaborative; Research; EDGE; CMT; Predicting

Wildlife infectious diseases can cause extinctions and populations declines in animals, often also impacting public health. Sylvatic (better known as bubonic) plague was introduced to North America in 1900 and is now maintained in native mammals in the western U.S., periodically eliciting disease outbreaks. Although some species seem to have natural resistance, others—such as prairie dogs—are highly susceptible. Despite the detection of plague resistance in a small number of prairie dogs, the disease still decimates populations throughout their range. The continued susceptibility of prairie dogs suggests there is some constraint inhibiting the widespread evolution of resistance to plague. This project uses whole-genome and transcriptome sequencing of resistant and susceptible prairie dogs to determine the genomic basis of recently evolved plague resistance. Mutations associated with resistance in natural populations and experiments will then be mapped in nature to determine the spatial distribution of resistance alleles and predict the location of potential resistance hotspots. Museum specimens of prairie dogs will also be genotyped to determine the rate of evolution of plague resistance. Given the increasing rate of novel pathogens emerging around the globe, this research will have broad implications for understanding when and where adaptation in naïve hosts is likely to persist. This project will use research to enhance education by building capacity in universities serving Native American and Hispanic students. Traveling genomics workshops will be delivered to students and faculty, and students will be mentored at their own institutions as they conduct independent research in the system.Adaptation to pathogens should be heavily favored by selection: Once immunity evolves, it should sweep to fixation across a species’ range. Paradoxically, a more commonly observed pattern is variable immunity. Because there are multiple explanations for incomplete resistance, the ecological and evolutionary conditions under which resistance to novel pathogens is maintained are still poorly understood. For instance, to what extent does the habitat matrix influence the maintenance of resistance through processes such as gene dilution? Does the de novo evolution of resistance independently across populations lead to epistatic interactions preventing widespread resistance? Resistance to sylvatic plague (caused by the bacterium Yersinia pestis) has been observed in prairie dogs (genus Cynomys) in six western states, but resistance is still rare. This project integrates genomic and transcriptomic analysis of experimentally infected animals with rangewide spatiotemporal sampling to elucidate how, when and where resistance evolves, and what prevents this adaptive trait from sweeping to fixation. Previous experimental infections and a natural epizootic will be used to determine the genomic basis of resistance in two species. Alleles associated with resistance, along with neutral alleles serving as a null model, will be genotyped in latitudinal transects spanning populations with different plague introduction times, and in museum specimens from at least three distinct time ranges. These data will enable estimates of the rate of evolution of resistance alleles and inferences of the landscape spatial structure and genomic characteristics facilitating resistance. Understanding how adaptation persists across space and time can enable facilitated adaptation in imperiled systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

野生动物传染病可能导致动物灭绝和数量下降，通常还会影响公共健康。森林鼠疫(更为人所知的是腺鼠疫)于1900年传入北美，现在在美国西部的本土哺乳动物中持续存在，定期引发疾病暴发。虽然有些物种似乎具有天然抵抗力，但其他物种--如草原土拨鼠--则高度敏感。尽管在少数草原土拨鼠中发现了对鼠疫的抵抗力，但这种疾病仍然在其活动范围内导致种群大量死亡。草原土拨鼠的持续易感性表明，有一些制约因素抑制了对鼠疫抗性的广泛进化。该项目使用抗性和易感草原犬的全基因组和转录组测序来确定最近进化的鼠疫抗性的基因组基础。自然种群和实验中与抗性相关的突变将被绘制在自然界中，以确定抗性等位基因的空间分布，并预测潜在的抗性热点的位置。博物馆的草原土拨鼠标本也将进行基因分型，以确定鼠疫抵抗力的进化速度。鉴于全球出现新病原体的速度越来越快，这项研究将对理解幼稚宿主的适应可能在何时何地持续具有广泛的意义。该项目将利用研究通过建设服务于美洲原住民和西班牙裔学生的大学的能力来加强教育。将为学生和教职员工举办巡回基因组学研讨会，学生在自己的机构进行系统中的独立研究时将得到指导。对病原体的适应应该受到选择的大力支持：一旦免疫进化，它应该席卷到一个物种的范围内。矛盾的是，一种更常见的观察模式是可变免疫。由于对不完全抗药性有多种解释，因此对新病原体维持抗药性的生态和进化条件仍然知之甚少。例如，栖息地基质通过基因稀释等过程在多大程度上影响抗性的维持？跨种群独立的抗药性从头进化是否导致上位性相互作用阻止广泛的抗药性？在西部六个州已经观察到草原犬(Cynomys属)对森林鼠疫(由鼠疫杆菌引起)的抗药性，但抗药性仍然很少。该项目将对实验感染动物的基因组和转录组分析与范围内的时空采样相结合，以阐明耐药性是如何、何时和在哪里演变的，以及是什么阻止了这种适应特征从席卷到固定。以前的实验感染和自然流行性疾病将被用来确定两个物种的抗药性的基因组基础。与抗性相关的等位基因，以及作为零模式的中性等位基因，将在横跨不同鼠疫传入时间的种群的纬向横断面中进行基因分型，并在至少三个不同时间范围的博物馆标本中进行基因分型。这些数据将有助于估计抗性等位基因的进化速度，并推断促进抗性的景观空间结构和基因组特征。了解适应如何在空间和时间上持续存在，可以促进在危险系统中的适应。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。