Characterization of the hypoxia-inducible factor 1 alpha gene in the sperm whale, beluga whale, and Yangtze finless porpoise

Cetaceans have evolved many behavioral and biological adaptations to allow them to survive in aquatic environments. Because of diving and breath-holding behaviors, cetaceans experience wide fluctuations in oxygen tension. However, the molecular basis behind their adaptation to a wide range of diving depths and durations remains unknown. Hypoxia-inducible factor (HIF) is a crucial regulator of cellular and systemic responses to low oxygen levels. In this study, the HIF-1 alpha gene was cloned from the sperm whale (Physeter macrocephalus), the beluga whale (Delphinapterus leucas), and the Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis). HIF-1 alpha from the deep-diving sperm whale degraded rapidly under normoxia but remained stable during hypoxia compared with HIF-1 alpha from the beluga whale and the Yangtze finless porpoise. Sperm whale HIF-1 alpha also responded to reoxygenation significantly faster and exerted more potent effects on the transcriptional activity of some gene promoters compared with HIF-1 alpha from the beluga whale and the Yangtze finless porpoise. Mutations in HIF-1 alpha were detected between the Yangtze finless porpoise and the sperm whale, which may determine their functional differences. The results suggest that the response of sperm whale HIF-1 alpha to different oxygen tensions is more variable than that of Yangtze finless porpoise or beluga whale HIF-1 alpha, indicating that the rate of degradation of HIF-1 alpha may be more variable in long-duration divers than in short-duration diver cetaceans. Because of the lack of whale models and whale cell lines, all experiments were conducted in vitro using human embryonic kidney 293T cells.