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

高原小鼠适应低氧环境的生理机制

• 批准号: 580277-2022
• 负责人: Scott, GrahamGR
• 金额: $ 7.27万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=745466
• 关键词: Physiological; mechanisms; adaptation; low; oxygen

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.

高海拔哺乳动物进化出了精妙的生理适应能力，能够在模拟人类和动物疾病状态的慢性缺氧(缺氧)条件下生存和发挥功能。因此，在长期居住在高海拔地区的原住民中识别自然进化的低氧适应机制可以产生对生物科学产生广泛影响的发现，并可以为复杂特征的进化提供一般性见解。我们的合作将阐明两种极端高海拔啮齿动物低氧适应的机制基础：鹿鼠(Permyscus Manulatus)，它是北美哺乳动物中海拔范围最广的；安第斯叶耳鼠(Phyllotis Vvarum)，一种极端嗜热物种，保持着世界上栖息高度最高的哺乳动物的记录，也是最宽的海拔范围(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，有氧能力是一种复杂的表现特征，是适应和低氧适应的基础；(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促进生物组织不同等级水平的表型变化；以及(4)准确定位在不同物种的低氧适应中具有保守作用的基因和途径。我们的合作将通过阐明复杂性状中适应性进化变化的保守机制来推动该领域的发展。HQP将在重要的综合研究方法方面得到支持和培训，这些方法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关键研究挑战。因此，我们的合作将有助于我们在环境变化生物学方面增强加拿大的实力和领导力，并可能启发人类和动物治疗与缺氧相关的疾病的新方法。