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

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现在也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、可传播的癌症，它威胁到塔斯马尼亚魔鬼的灭绝。作为典型的传染病，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，长期数据表明，魔鬼和它们的肿瘤正在进化，以应对彼此的反应，但它们做出反应的遗传途径仍然描述得很少。这项研究的目的是确定魔鬼适应变化的潜在遗传路径，如一旦感染后存活率增加，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，也将进行肿瘤基因进化在时间和空间上的重复性测试。这项工作的影响是深远的。例如，如果种群间的遗传途径相似，则可以推广保护和治疗方案。相反，如果遗传途径不同，治疗方案可能需要量身定做，针对不同的人群进行不同的治疗。无论如何，这项工作将改善对标志性的塔斯马尼亚魔鬼的保护和管理。此外，塔斯马尼亚魔鬼癌症的进化与人类癌症非常相似，为追踪自然人群中肿瘤的进化提供了独特的机会。当今生命科学中最大的挑战之一是解开基因-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，强毒EID在传播时会对多个寄主群体施加巨大的选择压力，为测试寄主-病原体进化中的重复性模式提供了一种方法。塔斯马尼亚魔鬼及其致命的可传染癌症是此类测试的模型系统。整个塔斯马尼亚地区从东到西的疾病出现过程创造了一个自然的实验。不同的魔鬼种群已经感染了不同的世代，处于疾病发展的不同进化阶段。数以千计的疾病和健康魔鬼的表型测量，以及魔鬼-肿瘤对的广泛组织采样，将使(共同)进化的分子特征的稳健测试成为可能。基因组扫描和进化一致性分析将用于测试魔鬼和肿瘤的适应性表型特征背后的基因组架构是否在时间上(即，跨越疾病出现的不同阶段)和空间(即，跨越不同的人群)可重复。如果一致，将测试潜在的机制(例如，软选择性扫描、硬扫描或基因流)。该奖项反映了NSF的法定使命，并已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。

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.