The hypoxia response pathway in the Antarctic fish Notothenia coriiceps is functional despite a poly Q/E insertion mutation in HIF-1α

Abstract

Antarctic notothenioid fishes, inhabiting the oxygen-rich Southern Ocean, possess a polyglutamine and glutamic acid (poly Q/E) insertion mutation in the master transcriptional regulator of oxygen homeostasis, hypoxia- inducible factor-1α (HIF-1α). To determine if this mutation impairs the ability of HIF-1 to regulate gene expression in response to hypoxia, we exposed Notothenia coriiceps, with a poly Q/E insertion mutation in HIF-1α that is 9 amino acids long, to hypoxia (2.3 mg L⁻¹ O₂) or normoxia (10 mg L ⁻¹ O₂) for 12 h. Heart ventricles, brain, liver, and gill tissue were harvested and changes in gene expression quantified using RNA sequencing. Levels of glycogen and lactate were also quantified to determine if anaerobic metabolism increases in response to hypoxia. Exposure to hypoxia resulted in 818 unique differentially expressed genes (DEGs) in liver tissue of N. coriiceps. Many hypoxic genes were induced, including ones involved in the MAP kinase and FoxO pathways, glycolytic metabolism, and vascular remodeling. In contrast, there were fewer than 104 unique DEGs in each of the other tissues sampled. Lactate levels significantly increased in liver in response to hypoxia, indicating that anaerobic metabolism increases in response to hypoxia in this tissue. Overall, our results indicate that the hypoxia response pathway is functional in N. coriiceps despite a poly Q/E mutation in HIF-1α, and confirm that Antarctic fishes are capable of altering gene expression in response to hypoxia.