Fish models to explore epigenetic determinants of hypoxia-tolerance

The occurrence of environmental hypoxia in freshwater and marine aquatic systems has increased over the last century and is predicted to further increase with climate change. As members of the largest extant vertebrate group, freshwater fishes, and to a much lesser extent marine fishes, are vulnerable to increased occurrence of hypoxia. This is important as fishes render important ecosystem services and have important cultural and economic roles. Evolutionarily successful, fishes have adapted to diverse aquatic freshwater and marine habitats with different oxygen conditions. While some fishes exhibit genetic adaptions to tolerate hypoxia and even anoxia, others are limited to oxygen-rich habitats. Recent advances in molecular epigenetics have shown that some epigenetic machinery, especially histone- and DNA demethylases, is directly dependent on oxygen and modulates important transcription-regulating epigenetic marks in the process. At the post-transcriptional level, hypoxia has been shown to affect non-coding microRNA abundance. Together, this evidence adds a new molecular epigenetic basis to study hypoxia tolerance in fishes. Here, we review the documented and predicted changes in environmental hypoxia in aquatic systems and discuss the diversity and comparative physiology of hypoxia tolerance in fishes, including molecular and physiological adaptations. We then discuss how recent mechanistic advances in environmental epigenetics can inform future work probing the role of oxygen-dependent epigenetic marks in shaping organismal hypoxia-tolerance in fishes with a focus on within- and between-species variation, acclimation, inter- and multigenerational plasticity, and multiple climate-change stressors. We conclude by describing the translational potential of this approach for conservation physiology, ecotoxicology, and aquaculture.