Physiology of hypoxia adaptation in the worlds highest-dwelling mammal

该研究项目旨在发现生活在安第斯山脉极高海拔地区的小鼠如何能够在极端寒冷和缺氧（缺氧）的情况下生存和发挥作用。研究物种，Phyllotis vaccarum，保持着世界上最高居住的哺乳动物的记录，它也有迄今为止最广泛的海拔范围。该物种从海平面一直分布到海拔6700米（22，000 '）的安第斯山脉。由于其非常广泛的海拔范围和极端的耐缺氧性，Phyllotis vaccarum是一个理想的研究物种，以解决有关高海拔适应的生理机制和这些机制的进化方式的问题。这些发现将为与原产于安第斯高原和青藏高原极高海拔地区的人群进行比较提供基础，并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则。这项研究可能会产生新的发现，因为生活在如此极端海拔的哺乳动物从未被实验研究过。该项目包括一个针对智利和北美机构学员的国际交流计划。该研究项目将研究安第斯小鼠物种（Phyllotis vaccarum）的缺氧适应机制，该物种生活在比世界上任何其他哺乳动物物种都高得多的海拔，也是迄今为止海拔范围最广的物种。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相一致的程度的基本问题。对遗传和环境诱导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作用或拮抗作用的实验见解将促进我们对生理适应和复杂生理表型演变过程的理解。为了确定和表征缺氧驯化和适应的机制，将使用普通花园实验设计来检查从该物种范围的对比高海拔和低海拔极端采样的叶耳鼠自然种群之间的生理差异。系统生理学的实验分析将涉及测量全动物生理性能（缺氧产热能力）和纯种、圈养繁殖的高地和低地小鼠的一整套从属性状。由于Phyllotis vaccarum生活在以前被认为完全不适合居住的海拔高度，在这种脊椎动物极端环境中的缺氧适应机制的鉴定将在比较/进化生理学中具有变革性价值。该奖项反映了NSF的法定使命，并被认为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来支持。

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.