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

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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.