Transcriptomic Adjustment to Decreasing Oxygen Reveals Novel Functional Strategies for Extreme Hypoxia Tolerance in...

Hypoxia-induced regulatory changes are well understood across aquatic and terrestrial systems. These changes are normally initiated by elements belonging to hypoxia-inducible factor (HIF) pathway. These elements generate responses that help organisms survive hypoxia, such as protein stabilization, antioxidant activity, or the switch from aerobic to anaerobic metabolism. The HIF pathway is initiated by the transcription factor HIF-α via deactivation of its repressor EGLN. However, recent work revealed that many aquatic invertebrates do not possess HIF-α or EGLN. Among these is the intertidal copepod Tigriopus californicus. Although this copepod experiences daily bouts of hypoxia, T. californicus tolerates even extended anoxia with minimal mortality. Because T. californicus lacks HIF-α, it is unclear how the transcriptional response proceeds on a fine timescale in this species and which physiological strategies they use to cope with severe hypoxia. In this study, we captured gene expression over a species-typical course of hypoxia including normoxia, mild hypoxia (∼3.5 mg O2 L-1), at critical oxygen tension (Pcrit; ∼0.5 mg O2 L-1), anoxia (0 mg O2 L-1), and recovery. We identified and clustered genes affected by this hypoxia course and tested for enrichment of Gene Ontology and transcription factor binding site motifs. We identified genes with known responses to hypoxia, including genes with interactions with HIF-α in other systems. We also identified genes related to functions unique to T. californicus, including exoskeletal modifications that could represent a specialized response allowing T. californicus to persist in extreme hypoxic environments despite lacking HIF-α.