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

适应高海拔环境对诸如哺乳动物等强烈依赖代谢产生的热量来维持体温的吸热（“温血”）动物提出了一些最极端的挑战。代谢产热主要通过氧依赖性（有氧）代谢发生，高海拔地区氧可用性降低（缺氧）可能会限制代谢产热的能力，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的缺氧和寒冷条件下生存。研究人员将结合生理、遗传和代谢研究，确定小鼠在不同海拔高度的潜在适应性特征，并使用建模方法将这些特征整合并将其与生物体联系起来？在不同环境下的适应性。虽然这项研究的重点是鹿鼠种群，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是高度保守的;因此，这项研究的发现将对理解包括人类在内的其他哺乳动物在高海拔种群中对寒冷和缺氧的生理适应具有意义。 该项目将研究与多样化和广泛的教育和公共宣传活动相结合，包括研究生和本科生的培训，促进国际合作，高中教师研讨会和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，有氧产热的能力提供了一个与达尔文适应性有明显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的能力，生活在高海拔的小型哺乳动物面临着双重束缚，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。与这些预期的健身效果一致，生存研究的高海拔鹿小鼠（Peromyscus maniculatus）已经揭示了强有力的定向选择缺氧条件下的产热能力。本研究项目的目标是确定适应性种群差异的机制基础之间的产热能力鹿小鼠是本地不同海拔。研究人员将在圈养繁殖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特化在适应不同海拔高度中的作用。整个动物产热能力的措施将与各种从属性状的措施和潜在的调控网络的功能基因组分析相结合。这种系统级分析的规模涉及复杂的建模工作，以整合一套全面的生理，遗传和代谢变量，以前从未尝试过。 这项研究将产生重要的见解的生理适应缺氧和寒冷暴露的综合挑战的机制基础。这项研究涉及与加拿大麦克马斯特大学研究人员的重要合作，他们拥有进行某些实验所需的专业知识和设施。国外合作的一个组成部分将是在麦克马斯特大学为来自内布拉斯加大学林肯分校和伊利诺伊大学厄巴纳-香槟分校的本科生提供研究经验。本科生的研究经验是由国际和综合活动办公室的国际科学和工程科共同资助。关于极端环境中生活的故事对公众的想象力产生了强大的吸引力，调查人员将利用这种魅力来制定一项以内布拉斯加州立大学博物馆的“科学家星期天”计划为中心的公共宣传计划。将为公众制定方案，重点是“适应极端环境”。在伊利诺伊大学厄巴纳-香槟分校，研究人员将参与一系列进化生物学研讨会，旨在帮助高中教师开发工具和有效的方法，使用本研究的例子教授进化生物学。

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.