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: 2220818
• 负责人: Ana Davidson
• 金额: $ 70.87万
• 依托单位: Colorado State University
• 依托单位国家: 美国
• 项目类别: Standard 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=2220818&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.

野生动物传染病可导致动物灭绝和数量下降，通常还会影响公众健康。森林鼠疫于 1900 年传入北美，目前在美国西部的本土哺乳动物中存在，定期引发疾病爆发。尽管某些物种似乎具有天然抵抗力，但其他物种（例如土拨鼠）却高度敏感，尽管在少数土拨鼠中发现了鼠疫抵抗力，但这种疾病仍然导致其种群数量大量减少。草原土拨鼠的持续易感性表明，存在一些抑制鼠疫抗性广泛进化的因素。该项目使用抗性和易感性土拨鼠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。然后，我们将在自然种群和实验中绘制出耐药性的图谱，以确定耐药性等位基因的空间分布，并预测潜在耐药性热点的位置。博物馆的草原土拨鼠标本也将进行基因分型，以确定耐药率。鉴于全球范围内新病原体出现的速度不断增加，这项研究将对了解幼稚宿主的适应何时何地可能持续存在具有广泛的意义。该项目将利用研究通过大学能力建设来加强教育。将为美国原住民和西班牙裔学生提供巡回基因组学研讨会，学生将在自己的机构中在系统中进行独立研究时得到指导。对病原体的适应应该受到选择的青睐：一旦免疫力进化，它应该扫过固定矛盾的是，更常见的模式是可变免疫，因为对不完全抗性有多种解释，但对新病原体的抗性维持的生态和进化条件仍然知之甚少。栖息地基质通过基因稀释等过程影响抵抗力的维持？种群间抵抗力的从头进化是否会导致上位相互作用，从而阻止对森林鼠疫（由鼠疫杆菌引起）的抵抗力？在西部六个州的草原土拨鼠（草原犬鼠属）中观察到耐药性仍然很少见，该整合项目通过广泛的时空采样对实验感染的动物进行基因组和转录组分析，以阐明耐药性如何、何时何地进化，以及是什么阻止了这种适应性特征。从扫描到固定，将使用先前的实验感染和自然流行病来确定与耐药性相关的等位基因以及作为无效模型的中性等位基因。在跨越不同鼠疫传入时间的种群的纬度横断面以及至少三个不同时间范围的博物馆标本中进行基因分型，这些数据将能够估计抗性等位基因的进化速率，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，可以促进危险系统中的适应。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。