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世纪全球面临的主要挑战。除了对人类健康的极大关注外，EID现在是生物多样性下降的主要原因。一个众所周知的例子是一种致命的传染性癌症，它威胁着塔斯马尼亚恶魔的灭绝。典型的传染病，宿主进化以抵抗病原体。反过来，病原体被迫进化以克服新的宿主防御。事实上，长期数据显示，魔鬼和它们的肿瘤正在相互进化，但它们做出反应的遗传途径仍然缺乏描述。这项研究的目的是确定魔鬼适应性变化的遗传途径，例如感染后生存率的增加，在感染不同时间的魔鬼种群中是否相似或不同。同样，肿瘤已经适应，也将进行肿瘤遗传进化在时间和空间上的可重复性测试。这项工作的影响是深远的。例如，如果种群之间的遗传途径相似，则可以推广保护和治疗方案。相反，如果遗传途径不同，则可能需要量身定制治疗方案，对不同人群采用不同的治疗方法。无论如何，这项工作将改善对标志性塔斯马尼亚魔鬼的保护和管理。此外，袋獾癌症的演变与人类癌症非常相似，这为在自然人群中跟踪肿瘤演变提供了独特的机会。当今生命科学的最大挑战之一是解开基因型-表型关系。快速的全球变化需要评估物种的适应能力，以及适应性进化是否可重复，以指导适当的管理战略。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，毒性EID可以征收强烈的选择压力，多个主机种群，因为它们的传播，提供了一种方法来测试模式的可重复性在主机病原体的进化。袋獾及其致命的传染性癌症是此类测试的模型系统。塔斯马尼亚州疾病出现的东向西进展创造了一个自然实验。不同的魔鬼种群已经感染了不同数量的世代，并且处于疾病进展的不同进化阶段。沿着对患病和健康魔鬼的数千个表型测量，以及对魔鬼-肿瘤对的广泛组织取样，将使对（共同）进化的分子特征的强有力的测试成为可能。基因组扫描和进化一致性分析将用于测试魔鬼和肿瘤中适应性表型性状的基因组结构是否在时间上是可重复的（即，跨越疾病出现的不同阶段）和空间（即，不同人群）。如果一致，则说明潜在机制（例如，该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。