Physiology of hypoxia adaptation in the worlds highest-dwelling mammal

这个研究项目是为了发现生活在安第斯山脉极高海拔地区的老鼠是如何在极度寒冷和缺氧的情况下生存和发挥功能的。该研究物种是世界上居住海拔最高的哺乳动物，也是迄今为止海拔范围最广的哺乳动物。该物种从海平面持续分布到海拔6700米（22000英尺）的安第斯山脉的顶峰。由于其海拔范围非常广，具有极强的耐缺氧性，是研究高海拔适应生理机制及其进化方式的理想研究物种。这些发现将为与安第斯高原和青藏高原极高海拔地区的土著人口进行比较提供基础，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，因为从未对生活在如此极端海拔地区的哺乳动物进行过实验研究。该项目包括为来自智利和北美机构的学员提供国际交流计划。本研究项目将研究一种安第斯小鼠（Phyllotis vaccum）的缺氧适应机制，这种小鼠生活在比世界上任何其他哺乳动物都高得多的海拔上，也是迄今为止海拔范围最广的。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。通过实验了解基因和环境诱导的低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，将促进我们对生理适应和复杂生理表型进化过程的理解。为了确定和描述低氧适应和适应的机制，我们将使用一个普通花园实验设计来检查从该物种范围的高海拔和低海拔极端地区取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包括对纯种、圈养的高原和低地小鼠的全动物生理性能（缺氧时的产热能力）和一套全面的从属性状的测量。由于真空Phyllotis真空Phyllotis真空Phyllotis真空Phyllotis真空Phyllotis真空Phyllotis真空Phyllotis真空Phyllotis真空Phyllotis真空Phyllotis真空Phyllotis真空Phyllotis真空真空Phyllotis真空真空真空真空真空真空真空真空真空真空真空真空真空真空真空真空真空真空真空真空真空真空真空真空真空真空真空该奖项反映了美国国家科学基金会的法定使命，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。

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.