Evolution and Plasticity of Muscle Metabolism

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The evolutionary aspects of muscle metabolism have not been extensively studied, despite the importance of appropriate fuel substrate allocation for effective locomotion, thermogenesis, and whole-body metabolic homeostasis. Species variation in muscle capacity for fuel use, and the response to environmental stress, results from interactions between genotype and the plasticity of muscle phenotype occurring at physiological time scales (developmental and adult plasticity). The long-term objective of my research program is to understand how fuel delivery and utilization pathways evolve and respond to energetic and environmental stress to support the dynamic energetic changes seen in this tissue. Animals who live in the high altitude (HA) are ideal models to study the evolution and plasticity of muscle metabolism to the known stressors of low oxygen and temperature. Thus, we use deer mice (Peromyscus maniculatus) bred in common conditions from separate parental stocks from populations at low altitude (LA) and HA . This allows us to distinguish genetically fixed traits from those that undergo environmental induced plasticity. Previously, we have found that high altitude deer mice (i) rely to a greater extent in carbohydrate oxidation to power exercise, in part due to evolved phenotypic plasticity to hypoxia compared to low altitude mice. (ii) Deer mice support thermogenesis with high rates of fatty acid oxidation (FAO), which is higher in HA and LA mice and shows robust phenotypic plasticity. and (ii) Early life events can impact survival and adult phenotypes, and we uncovered population differences in how endothermy develops in deer mice but also in how postnatal cold or cold & hypoxia impact adult thermogenic capacity. In the next 5 years I will address 3 objectives to determine: 1. The underlying mechanisms of evolved differences in exercise fuel use at HA, 2. The regulation of FAO during thermogenesis at HA. and 3. The mechanisms responsible for postnatal environment impacts on adult metabolism and thermogenic capacity. I will address these objectives using our low and high altitude deer mice, and use exposures to chronic hypoxia or cold & hypoxia to uncover evolved differences in plasticity of subordinate traits that help explain adaptive differences in locomotory or thermogenic performance. Through breeding mice to the second generation we will study maternal care and environmental effects on the ontogeny of endothermy and the developmental plasticity of thermogenic capacity in high altitude deer mice. Unlike traditional rodent models, resulting data may uncover multiple different physiological "solutions" allowing species to either sustain high rates of fuel delivery, or to provide the optimal allocation of fuel to muscle for survive in low O2 or temperature environments. This research will train 10 B.Sc, 5 M.Sc. and 4 Ph.D. students.