Mechanisms and Evolution of Hypoxia Tolerance

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For most air-breathing vertebrates, decreases in environmental oxygen (referred to as hypoxia) are a rare occurrence; when they do occur, they can have devastating metabolic consequences resulting in death. In aquatic environments however, oxygen levels can vary substantially, from levels that are many-fold higher than normal to the complete absence of oxygen. As a result, it is not surprising that the water-breathing vertebrates that inhabit these diverse environments, particularly fish, show a high level of variation in hypoxia tolerance. Despite several decades of study, we still do not have a complete understanding of the factors that explain why there is variation in hypoxia tolerance among fish and the mechanisms that explain why some fish are more susceptible to the negative consequences of hypoxia exposure than others. To address this knowledge gap, my research program uses the natural variation in hypoxia tolerance observed among groups of closely related fish species to understand the mechanisms and evolution of hypoxia tolerance. Our primary comparative model involves multiple species of fish called sculpins, which we collect from the marine near shore environment and show a large variation in hypoxia tolerance. Based upon our work in sculpins and other comparative models, we have identified three major factors that contribute to explaining variation in hypoxia tolerance. First, we have identified the mitochondrion, which is often referred to as "the powerhouse of the cell", as a nexus of adaptation to hypoxia. Second, we have uncovered a unique gene expression signature that differentiates hypoxia tolerant and intolerant sculpins. Finally, we demonstrate that hypoxia tolerance is associated with the ability to "turn off" metabolism and suppress metabolic rate. This NSERC-DG proposal builds upon these major findings and aims to elucidate the detailed physiological, biochemical, and molecular mechanisms that define hypoxia tolerance. Research of this nature is important as it assists in predicting which organisms are most at risk due to human-induced climate change and the associated increases in aquatic hypoxia. In addition, our detailed mechanistic work is uniquely positioned to discover fundamental aspects of oxygen biology, which could assist in uncovering important pathways underlying oxygen related conditions in humans, including cancer and heart attack. This grant will allow me to train 5 graduate (3 PhD & 2 MSc) and 2 undergraduate (1 BSc Honors & 1 NSERC-USRA) students per year in the most advanced analytical and conceptual approaches for understanding how animals interact with their environment.