Hypoxia, or a lack of oxygen in the tissues, is a significant source of metabolic stress. It is a major component of many human diseases, including various forms of cancer. Remarkably, there are animals that display an impressive capacity to withstand lethal levels of hypoxia, providing models to better understand the hypoxic response in vertebrates. Such is the case for Brachyhypopomus, a genus of weakly electric fish that inhabit the Amazon, one of the most challenging aquatic ecosystems in the world. Dissolved oxygen levels deplete on a seasonal and often daily basis, requiring hypoxia tolerance for prolonged periods of time.
Ahmed A. Elbassiouny and colleagues have used closely related species’ of Brachyhypopomus displaying a range of hypoxia tolerances to investigate the molecular mechanisms of hypoxia-inducible factors (HIFs) – transcription factors known to coordinate the cellular response to hypoxia in vertebrates. They found that HIF1⍺ from hypoxia-tolerant Brachyhypopomus species displayed higher transactivation in response to hypoxia compared to intolerant species. Furthermore, two SUMO-interacting motifs appeared to facilitate the transactivation. Together with computational selection analyses which showed evidence for positive selection in Brachyhypopomus, they showed that the evolution of HIF1⍺ likely underlies adaptations to hypoxia tolerance for this group of fascinating fish.