Physiological mechanisms of adaptation to low-oxygen environments in high-altitude mice

高海拔哺乳动物已经进化出了精细的生理适应，能够在慢性缺氧（缺氧）条件下生存和运作，模仿人类和动物的疾病状态。因此，确定长期高海拔原住民自然进化的低氧适应机制可以在生物科学领域产生广泛影响的发现，并可以为复杂性状的进化提供一般见解。我们的合作将阐明两种极端高海拔啮齿动物缺氧适应的机制基础：鹿鼠（Peromyscus maniculatus），它在北美任何哺乳动物中具有最广泛的海拔范围；以及安第斯叶耳鼠（Phyllotis vaccum），这是一种极端微生物，是世界上居住海拔最高的哺乳动物，也是海拔最宽的物种（海平面至6700米）。我们的目标是：(1)确定有氧能力增强的生理机制，这是一种复杂的性能特征，是适应性和低氧适应的基础；(2)确定跨物种共享的保守机制；(3)确定基因表达的变化如何影响生物组织不同层次水平上的表型变化；(4)查明在物种缺氧适应中起保守作用的基因和途径。我们的合作将通过阐明复杂性状的适应性进化变化的保守机制来推进该领域。HQP将在重要的综合研究方法方面得到支持和培训，这将使他们能够应对未来关于动物如何适应具有挑战性和不断变化的环境的重要研究挑战。因此，我们的合作将有助于我们为加拿大在环境变化生物学方面的实力和领导地位的增长做出贡献，并可能激发人类和动物缺氧相关疾病的新治疗方法。

High-altitude mammals have evolved exquisite physiological adaptations to survive and function under conditions of chronic oxygen-deprivation (hypoxia) that mimic disease states in humans and animals. Identifying naturally evolved mechanisms of hypoxia adaptation in long-term high-altitude natives can therefore yield discoveries of broad impact across biological sciences, and can provide general insights into the evolution of complex traits. Our collaboration will elucidate the mechanistic basis of hypoxia adaptation in two extreme high-altitude rodents: the deer mouse (Peromyscus maniculatus), which has the broadest altitudinal range of any North American mammal; and the Andean leaf-eared mouse (Phyllotis vaccarum), an extremophile species that holds the record as the world's highest dwelling mammal as well as the broadest altitudinal range (sea level to >6700 m). Our objectives are to (1) define the physiological mechanisms underlying enhancements of aerobic capacity, a complex performance trait that underlies fitness and hypoxia adaptation, (2) identify conserved mechanisms that are shared across species, (3) determine how changes in gene expression contribute to changes in phenotype at different hierarchical levels of biological organization; and (4) pinpoint genes and pathways that have conserved roles in hypoxia adaptation across species. Our collaboration will advance the field by elucidating conserved mechanisms of adaptive evolutionary change in complex traits. HQP will be supported and trained in important integrative research approaches that will allow them to tackle vital research challenges of the future about how animals will adapt to challenging and ever-changing environments. Our collaboration will thus help us contribute to growth of Canadian strength and leadership in the biology of environmental change, and may inspire novel treatments for hypoxia-related diseases in humans and animals.