Collaborative Research: Testing the spatio-temporal repeatability of (co)evolution in Tasmanian devils and their transmissible cancer

合作研究：测试塔斯马尼亚恶魔及其传染性癌症的（共同）进化的时空重复性

• 批准号: 2324456
• 负责人: Mark Margres
• 金额: $ 61.61万
• 依托单位: University of South Florida
• 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: 2023-08-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2324456&HistoricalAwards=false
• 关键词: Collaborative; Research; Testing; spatio; temporal

Emerging infectious diseases (EIDs) are a leading global challenge in the 21st century. In addition to their great concern for human health, EIDs are now a leading cause of biodiversity declines. A well-known example is a lethal, transmissible cancer that threatens Tasmanian devils with extinction. Typical of infectious diseases, the host evolves to resist the pathogen. In turn, the pathogen is pressured to evolve to overcome new host defenses. Indeed, long-term data show that devils and their tumors are evolving in response to one another, but the genetic pathways by which they respond remain poorly described. The goal of this research is to determine whether the genetic pathways underlying adaptive changes in devils, such as increased survival once infected, are similar or different among devil populations infected for different lengths of time. Similarly, the tumor has adapted, and tests of repeatability of tumor genetic evolution in time and space will also be conducted. The implications of this work are far reaching. If, for example, genetic pathways are similar among populations, then conservation and treatment options can be generalized. Conversely, if genetic pathways are different, treatment options may need to be tailored, with different treatments for different populations. Regardless, the work will lead to improved conservation and management of the iconic Tasmanian devil. Additionally, the Tasmanian devil cancer evolves quite similarly to human cancer, providing a unique opportunity to track tumor evolution in a natural population.One of the biggest challenges in the life sciences today is unraveling the genotype-phenotype relationship. Rapid global change necessitates assessments of species’ capacity to adapt and whether adaptive evolution is repeatable to guide appropriate management strategies. Owing to the polygenic nature of most phenotypic traits, this is a formidable task. However, virulent EIDs can levy intense selection pressure on multiple host populations as they spread, offering a way to test patterns of repeatability in host-pathogen evolution. Tasmanian devils and their lethal transmissible cancer are a model system for such tests. The east-to-west progression of disease emergence across Tasmania has created a natural experiment. Different devil populations have been infected for different numbers of generations and are at different evolutionary stages of disease progression. Thousands of phenotypic measurements of diseased and healthy devils, along with extensive tissue sampling of devil-tumor pairs, will enable robust tests of molecular signatures of (co)evolution. Genome scans and evolutionary concordance analyses will be used test whether the genomic architecture underlying adaptive phenotypic traits in devils and tumors are repeatable in time (i.e., across different stages of disease emergence) and space (i.e., across different populations). If concordant, the underlying mechanism (e.g., soft selective sweeps, hard sweeps or gene flow) will be tested.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.

新发传染病 (EID) 是 21 世纪的主要全球挑战，除了对人类健康的极大关注外，EID 现在也是生物多样性下降的主要原因，一个众所周知的例子是威胁塔斯马尼亚的致命传染性癌症。獾类病毒是一种典型的传染病，宿主会进化以抵抗病原体，而病原体则被迫进化以克服新的宿主防御。事实上，长期数据表明，獾类及其肿瘤。正在进化以响应彼此，但它们做出反应的遗传途径仍然很少被描述。这项研究的目的是确定袋獾适应性变化（例如感染后存活率的提高）背后的遗传途径是否相似或不同。同样，肿瘤也已适应，并且也将进行肿瘤遗传进化在时间和空间上的可重复性测试，例如，如果遗传途径被证实，那么这项工作的意义是深远的。人群之间相似，那么可以推广保护和治疗方案。同时，如果遗传途径不同，可能需要调整治疗方案，同样，这项工作将改善标志性人类癌症的保护和管理，为追踪肿瘤提供独特的机会。自然种群的进化。当今生命科学面临的最大挑战之一是阐明基因型与表型的关系，因此需要评估物种的适应能力以及适应性进化是否可重复。由于大多数表型性状的多基因性质，这是一项艰巨的任务，然而，有毒的EID在传播时会对多个宿主群体施加强烈的选择压力，从而提供了一种测试宿主重复性模式的方法。塔斯马尼亚袋獾及其致命的传染性癌症是此类测试的模型系统。塔斯马尼亚各地疾病出现的从东到西的进展创造了一个自然实验。对患病和健康的袋獾进行数以千计的表型测量，以及对袋獾-肿瘤对进行广泛的组织采样，将能够对（共同）进化的分子特征进行可靠的测试。进化一致性分析将用于测试袋獾和肿瘤适应性表型特征的基因组结构是否在时间（即，在疾病出现的不同阶段）和空间（即，在不同种群）上可重复。一致的，底层机制（例如，软选择性扫描、硬扫描或基因流）将受到测试。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优点和更广泛的影响审查标准进行评估，被认为值得支持。