Physiology of hypoxia adaptation in the worlds highest-dwelling mammal

世界上栖息地最高的哺乳动物缺氧适应的生理学

• 批准号: 2114465
• 负责人: Jay Storz
• 金额: $ 82.73万
• 依托单位: University of Nebraska-Lincoln
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2114465&HistoricalAwards=false
• 关键词: Physiology; hypoxia; adaptation; worlds; highest

This research project is to discover how mice living at extremely high elevations in the Andes are able to survive and function in spite of extreme cold and lack of oxygen (hypoxia). The study species, Phyllotis vaccarum, holds the record as the world’s highest-dwelling mammal, and it also has by far the broadest altitudinal range. The species is continuously distributed from sea level to the crest of the Andes at 6700 m (22,000’). Because of its extraordinarily broad elevational range and extreme hypoxia tolerance, Phyllotis vaccarum is an ideal study species to address questions about physiological mechanisms of high-altitude adaptation and the way such mechanisms evolved. The discoveries will provide a basis for comparison with human populations that are native to extremely high elevations in the Andean Altiplano and the Tibetan Plateau, and there is the potential to identify general principles associated with genetic adaptation and physiological acclimatization to extreme environments. The research is likely to yield novel discoveries because mammals that live at such extreme elevations have never been experimentally studied. The project includes an international exchange program for trainees from the Chilean and North American institutions.This research project will investigate mechanisms of hypoxia adaptation in an Andean mouse species (Phyllotis vaccarum) that lives at altitudes far higher than any other mammal species in the world and which also has by far the broadest altitudinal range. The research project is designed to address fundamental questions regarding the role of phenotypic plasticity in environmental adaptation and the extent to which acclimatization responses generally align with genetic responses to selection. Experimental insights into the relative contributions of genetic and environmentally induced changes in hypoxia-responsive phenotypes – and the potential synergy or antagonism between them – will advance our understanding of physiological adaptation and the process by which complex physiological phenotypes evolve. To identify and characterize mechanisms of hypoxia acclimation and adaptation, a common-garden experimental design will be used to examine physiological differences between natural populations of leaf-eared mice sampled from contrasting high- and low-altitude extremes of the species’ range. The experimental analysis of systemic physiology will involve measurements of whole-animal physiological performance (thermogenic capacity in hypoxia) and a comprehensive set of subordinate traits in pedigreed, captive-bred highland and lowland mice. Since Phyllotis vaccarum lives at altitudes that were previously considered completely uninhabitable, identification of mechanisms of hypoxia adaptation in this vertebrate extremophile will have transformative value in comparative/evolutionary physiology.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.

该研究项目旨在探索生活在安第斯山脉极高海拔地区的小鼠如何在极度寒冷和缺氧（缺氧）的情况下生存并发挥作用。研究物种Phyllotis vaccarum 保持着世界上居住地最高的哺乳动物的记录，而且它还拥有迄今为止最广泛的海拔范围。该物种从海平面到海拔 6700 米（22,000 英尺）的安第斯山脉山顶连续分布。由于其极其广泛的海拔范围和极端的耐缺氧能力，Phyllotis vaccarum 是解决高海拔适应的生理机制及其进化方式问题的理想研究物种。这些发现将为与安第斯高原和青藏高原极高海拔地区的原住民进行比较提供基础，并且有可能确定与极端环境的遗传适应和生理适应相关的一般原理。这项研究可能会产生新的发现，因为从未对生活在如此极端海拔的哺乳动物进行过实验研究。该项目包括针对来自智利和北美机构的学员的国际交流计划。该研究项目将研究安第斯山小鼠（Phyllotis vaccarum）的缺氧适应机制，这种小鼠生活的海拔远高于世界上任何其他哺乳动物物种，并且具有迄今为止最广泛的海拔范围。该研究项目旨在解决有关表型可塑性在环境适应中的作用以及适应反应通常与选择的遗传反应一致的程度的基本问题。对遗传和环境引起的缺氧反应表型变化的相对贡献以及它们之间潜在的协同或拮抗作用的实验见解将增进我们对生理适应和复杂生理表型进化过程的理解。为了识别和表征缺氧适应和适应机制，将使用普通花园实验设计来检查从物种范围的高海拔和低海拔极端情况中取样的叶耳小鼠自然群体之间的生理差异。系统生理学的实验分析将涉及对纯系、圈养繁殖的高地和低地小鼠的整个动物生理性能（缺氧下的生热能力）和一套全面的从属性状的测量。由于Phyllotis vaccarum生活在以前被认为完全不适宜居住的海拔高度，因此鉴定这种脊椎动物极端微生物的缺氧适应机制将在比较/进化生理学方面具有变革性价值。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。