Non-Genetic Inheritance of Hypoxia Tolerance in Fishes: Dynamics and Mechanisms

该项目将量化模型鱼对低氧耐受性的遗传，然后在生物体到分子水平上确定从父母传递给后代的耐受机制。研究人员将不仅关注传统的、经过充分研究的遗传机制，而且将探索所谓的“表观遗传”形式的遗传，这种遗传可能只会在一两代人中转移父母的特征。这种“临时遗传”实际上可能比更永久的遗传形式需要更少的能量，并且对物种更有益。由于短期气候变化和全球变暖，河流和湖泊中的低氧情况预计会增加，这些影响可能会因人为污染水平的增加而扩大。长期以来，鱼类对这种低氧条件的耐受性被认为是经历短期或长期低氧的鱼类种群生存的关键，但令人惊讶的是，人们对后代从父母那里遗传的生理学和解剖学知之甚少。该项目提供的信息将使生物学家能够更好地预测，甚至可能减轻未来河流和湖泊低氧事件的负面后果。完全融入研究项目是变革性的，国际研究经验（互动视频课程，交流访问，并涉及美国和墨西哥大学的研讨会）为种族多元化的本科生，研究生和博士后学员。一名博士后和一名本科生每年将直接参与综合研究，为科学培养目标做出贡献。鱼类的耐缺氧能力长期以来被认为是经历急性或慢性环境缺氧的种群生存的关键。由于全球变暖、气候随机性和污染增加，预计缺氧发作越来越频繁，这增加了对缺氧耐受性更深入了解的紧迫性。虽然我们知道有多少成鱼急性和慢性缺氧反应，令人惊讶的是，很少有人知道的非遗传（表观遗传）遗传的耐缺氧表型。因此，该项目将量化斑马鱼作为模式生物的缺氧耐受性的非遗传遗传，然后在亲本及其后代中从生物到分子水平确定潜在机制。具体而言，该项目将量化允许缺氧耐受性的非遗传遗传性状，确定“洗入”和“洗出”（即，耐缺氧表型在多代中的动态变化，并建立后代中非遗传的表观遗传机制。跨代非遗传遗传表型的潜在快速出现和消失使得在生物体到分子水平上了解鱼类种群如何科普未来的缺氧变得至关重要。此外，强大的国际培训部分将扩大美国和墨西哥大学的网络。参与的学生将通过双边密集研讨会，互动视频课程以及研究生对两国实验室项目的长期访问，增强对国际合作以及拉丁美洲和美国文化的欣赏。这将提供一个融合的科学和文化的经验，创造学员的生命科学研究的全球范围的第一手知识，以及科学经验的不同文化视角。这个奖项反映了NSF的法定使命，并已被认为是值得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的支持。

This project will quantify the inheritance of tolerance to low oxygen in a model fish and then determine the tolerance mechanisms, at organismal to molecular levels, that are passed on from parents to their offspring. The investigators will not only focus on conventional, well-studied genetic mechanisms for inheritance, but will explore so-called “epigenetic” forms of inheritance that may transfer parental characteristics for only a generation or two. Such “temporary inheritance” might actually require less energy and be more beneficial to a species than the more permanent form of genetic inheritance. Bouts of low oxygen in rivers and lakes are predicted to increase as a result of both short-term climate change and global warming, and these effects may be amplified by increasing levels of human-generated pollution. Tolerance of such low-oxygen conditions by fishes has long been recognized as vital for survival of fish populations that experience short- or long-term periods of low oxygen, but surprisingly little is understood about the inheritance from the parents by the offspring of the physiology and anatomy that allows such tolerance in fishes. The information provided by this project will allow biologists to better predict, and perhaps even mitigate, the negative consequences of future episodes of low oxygen in rivers and lakes. Fully integrated into the research project are transformative, international research experiences (interactive video courses, exchange visits, and workshops involving U.S. and Mexican universities) for ethnically diverse undergraduate, graduate and post-doctoral trainees. A post-doctoral fellow and an undergraduate student will participate directly in the integrative research each year, contributing to scientific training goals. Hypoxia tolerance in fishes has long been recognized as vital for survival of populations experiencing acute or chronic environmental hypoxia. Increasingly frequent bouts of hypoxia are predicted as a result of global warming, climate stochasticity, and increasing pollution, adding urgency to developing a deeper understanding hypoxia tolerance. While we know how many adult fishes acutely and chronically respond to hypoxia, surprisingly little is known about the non-genetic (epigenetic) inheritance of the hypoxia-tolerant phenotype. Consequently, this project will quantify non-genetic inheritance of hypoxia tolerance in zebrafish as a model organism and then identify underlying mechanisms, at organismal to molecular levels, in parents and in their progeny. Specifically, this project will quantify non-genetically inherited traits that allow hypoxia tolerance, determine “wash-in” and “wash-out” (i.e., the dynamics) of hypoxia-tolerant phenotypes across multiple generations, and establish epigenetic mechanism(s) of non-genetic inheritance in subsequent generations. The potentially rapid appearance and disappearance of transgenerational non-genetically inherited phenotypes makes it crucial to understand, at organismal to molecular levels, how fish populations may cope with future hypoxia. Additionally, a strong international training component will expand a network of U.S. and Mexican universities. Participating students will gain enhanced appreciation of both international collaboration and Latino and U.S. culture through bilateral intensive workshops, interactive video coursework, and longer-term visits by research students for laboratory-based projects in both countries. This will provide a merged scientific and cultural experience that creates in trainees a first-hand knowledge of the global reach of life science research, as well as different cultural perspectives of the science experience.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.