Research on the Mechanism of Hypoxia Tolerance of a Hybrid Fish Using Transcriptomics and Metabolomics

The novel hybrid fish BTB, derived from crossing blunt snout bream (<i>Megalobrama amblycephala</i>, BSB) and topmouth culter (<i>Culter alburnus</i>, TC), exhibits markedly hypoxia tolerance in aquaculture. In this study, hypoxic treatment experiments confirmed that, comparing to its original parent BSB, the tolerance to low oxygen of BTB increased by 20.0%. Furthermore, a comparative analysis of the transcriptome and metabolome was performed using gill tissues from BTB exposed to normoxic and hypoxic conditions. Under hypoxic conditions, BTB displayed adaptive modifications in gill lamellae and hemocytes. Transcriptomic profiling identified 789 differentially expressed genes (DEGs), with 298 upregulated and 491 downregulated, enriched in pathways including apoptosis, NK cell-mediated cytotoxicity, MAPK/TNF/Toll-like receptor signaling, and HIF-1/FoXO signaling pathways. Twelve hypoxia-related candidate genes (<i>egln3</i>, <i>im_7150988</i>, <i>znf395a</i>, <i>hif-1an</i>, <i>mknk2b</i>, <i>pck2</i>, <i>ero1a</i>, <i>igfbp-1a</i>, <i>vhl</i>, <i>bpifcl</i>, <i>egln1a</i>, and <i>ccna1</i>) were screened and validated as potential contributors to hypoxia tolerance. Metabolomics analysis revealed a total of 108 differential metabolites (78 upregulated and 30 downregulated), predominantly linked to Arginine and proline metabolism, Ether lipid metabolism, Arachidonic acid metabolism, and Glycerophospholipid metabolism. Association analysis of transcriptomics and metabolomics revealed that the DEGs and DMs were enriched in the pathways of glycerophospholipid metabolism, ether lipid metabolism, arachidonic acid metabolism, and arginine and proline metabolism. In summary, BTB exhibited relatively high hypoxia tolerance, and 12 candidate genes related to hypoxia tolerance were identified. These findings laid a foundation for further investigation into the mechanisms of hypoxia tolerance improvement in hybrid fish.