Collaborative Research: Mechanisms and evolution of thermogenic capacity in high-altitude deer mice

合作研究：高原鹿小鼠产热能力的机制和进化

• 批准号: 1354390
• 负责人: Jay Storz
• 金额: $ 22.49万
• 依托单位: University of Nebraska-Lincoln
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1354390&HistoricalAwards=false
• 关键词: Collaborative; Research; Mechanisms; evolution; thermogenic

Adaptation to high altitude environments poses some of the most extreme challenges for endothermic ("warm-blooded") animals such as mammals that strongly depend on metabolically generated heat for maintaining the body temperature. Metabolic heat generation occurs predominantly through oxygen-dependent (aerobic) metabolism, and reduced oxygen availability (hypoxia) at high altitude may limit the capacity for metabolic heat production and thus maintenance of the optimal body temperature. The PIs will use populations of deer mice adapted to different altitudes as a model to determine which physiological mechanisms permit them to survive under hypoxic and cold conditions of high altitudes. The PIs will use a combination of physiological, genetic and metabolic studies to identify the potentially adaptive traits in mice at different altitudes and use modeling approach to integrate these traits and link them to the organism?s fitness in different environments. Although this study focuses on the populations of deer mice, many molecular and physiological mechanisms of metabolic regulation and thermoregulation are highly conserved among the mammals; therefore, the findings of this study will have implications for understanding physiological adaptations to cold and hypoxia in high-altitude populations of other mammals including humans. This project integrates research with diverse and extensive educational and public outreach activities including training of graduate and undergraduate students, fostering international collaborations, workshops for high school teachers and public displays at a local museum. Elucidating the mechanistic underpinnings of adaptive trait variation is a central goal of evolutionary physiology. In small endotherms that live in cold environments, the capacity for aerobic thermogenesis provides an example of a whole-animal performance trait that has a clear connection to Darwinian fitness. Because hypoxia imposes constraints on the capacity for aerobic thermogenesis, small mammals living at high-altitude are faced with a double bind because their thermogenic capacity is compromised under conditions where thermoregulatory demands are especially severe. Consistent with these expected effects on fitness, survivorship studies of high-altitude deer mice (Peromyscus maniculatus) have revealed strong directional selection on thermogenic capacity under hypoxia. The goal of this research project is to identify the mechanistic basis of adaptive population differences in thermogenic capacity between deer mice that are native to different elevations. The investigators will conduct common-garden acclimation experiments in captive-bred, pedigreed mice to assess the roles of phenotypic plasticity and genotypic specialization in adaptation to different altitudes. Measures of whole-animal thermogenic capacity will be integrated with measures of various subordinate traits and a functional genomic analysis of the underlying regulatory networks. The scale of this systems-level analysis, which involves a sophisticated modeling effort to integrate a comprehensive set of physiological, genetic and metabolic variables, has never before been attempted. This research will yield important insights into the mechanistic basis of physiological adaptation to the combined challenges of hypoxia and cold exposure. This research involves an important collaboration with investigators at McMaster University in Canada, who have specialized expertise and access to facilities required for conduct of some experiments. A component of the foreign collaboration will be research experiences at McMaster University for undergraduate students from the University of Nebraska - Lincoln, and the University of Illinois Urbana-Champaign. The undergraduate research experiences are being supported by co-funding from the International Science and Engineering section of the Office of International and Integrative Activities. Stories about life in extreme environments exert a powerful hold on the public imagination, and the investigators will capitalize on this fascination to develop a public outreach program that is centered on the "Sunday with a Scientist" program at the University of Nebraska State Museum. Programs will be developed for the general public that will focus on 'adaptation to extreme environments'. At the University of Illinois Urbana-Champaign, researchers will be involved in a series of workshops in evolutionary biology aimed at assisting high school teachers to develop tools and effective approaches to teach evolutionary biology using examples from this research.

适应高海拔环境对吸热动物（“温血动物”）提出了一些最极端的挑战，例如哺乳动物，它们强烈依赖代谢产生的热量来维持体温。代谢性热的产生主要是通过氧依赖（有氧）代谢发生的，在高海拔地区，氧气可用性的降低（缺氧）可能会限制代谢性热产生的能力，从而限制最佳体温的维持。pi将使用适应不同海拔的鹿鼠种群作为模型，以确定哪些生理机制允许它们在高海拔低氧和寒冷的条件下生存。pi将结合生理、遗传和代谢研究来识别不同海拔地区小鼠的潜在适应性特征，并使用建模方法将这些特征整合起来，并将它们与生物体联系起来。S在不同环境下的适应度。虽然本研究主要集中在鹿鼠种群，但许多代谢调节和体温调节的分子和生理机制在哺乳动物中高度保守；因此，这项研究的发现将对理解包括人类在内的其他高海拔哺乳动物种群对寒冷和缺氧的生理适应具有重要意义。该项目将研究与各种广泛的教育和公共宣传活动结合起来，包括研究生和本科生的培训、促进国际合作、为高中教师举办的讲习班和在当地博物馆的公共展览。阐明适应性性状变异的机制基础是进化生理学的中心目标。在生活在寒冷环境中的小型恒温动物中，有氧产热能力提供了一个与达尔文适应度有明确联系的整体动物性能特征的例子。由于缺氧限制了有氧产热能力，生活在高海拔地区的小型哺乳动物面临着双重困境，因为它们的产热能力在温度调节要求特别严格的条件下受到损害。与这些对适应性的预期影响一致，高海拔鹿鼠（Peromyscus maniculatus）的生存研究揭示了缺氧条件下产热能力的强烈定向选择。本研究项目的目的是确定不同海拔地区的鹿鼠在产热能力方面的适应性种群差异的机制基础。研究人员将在圈养的纯种小鼠中进行普通花园驯化实验，以评估表型可塑性和基因型专业化在适应不同海拔的作用。全动物产热能力的测量将与各种从属性状的测量和潜在调节网络的功能基因组分析相结合。这种系统级分析的规模，包括一个复杂的建模工作，以整合一套全面的生理、遗传和代谢变量，以前从未尝试过。这项研究将对生理适应缺氧和寒冷暴露的机制基础产生重要的见解。这项研究涉及与加拿大麦克马斯特大学的研究人员的重要合作，他们具有专业知识，并且可以使用进行某些实验所需的设施。对外合作的一个组成部分将是让来自内布拉斯加大学林肯分校和伊利诺伊大学厄巴纳-香槟分校的本科生在麦克马斯特大学进行研究体验。本科生的研究经历由国际和综合活动办公室的国际科学与工程部门共同资助。关于极端环境下的生命的故事对公众的想象力有着强大的吸引力，调查人员将利用这种吸引力来开发一个以内布拉斯加大学州立博物馆的“周日与科学家”项目为中心的公众宣传项目。将为公众制定以“适应极端环境”为重点的项目。在伊利诺伊大学厄巴纳-香槟分校，研究人员将参与一系列关于进化生物学的研讨会，旨在帮助高中教师开发工具和有效的方法，使用本研究中的例子来教授进化生物学。