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

## TL;DR

A hybrid fish called BTB can survive in low-oxygen water better than its parents, and researchers found specific genes and metabolic changes that help it adapt.

## Contribution

The study identifies 12 key genes and specific metabolic pathways that contribute to hypoxia tolerance in hybrid fish.

## Key findings

- BTB hybrid fish showed a 20% increase in hypoxia tolerance compared to its parent species.
- Transcriptomic analysis revealed 789 differentially expressed genes linked to hypoxia response pathways.
- Metabolomic analysis identified 108 differential metabolites involved in lipid and amino acid metabolism under hypoxia.

## Abstract

A hybrid fish, called BTB, created by crossing two different species, showed a significantly improved ability for adapting in low-oxygen water compared to its parents, with a 20% increase in tolerance. However, the mechanism of hypoxia tolerance in BTB remained unclear. In this study, we found that gills physically adapted to hypoxia in BTB. By analyzing changes in genes and metabolites, potential biological pathways involved in stress response were identified. This study pinpointed 12 key genes that were likely responsible for responding to a hypoxic environment. Furthermore, we discovered that changes in lipid and amino acid metabolism (specifically in glycerophospholipid, ether lipid, arachidonic acid, and arginine/proline pathways) are involved in hypoxic response in fish. In short, this research identified the genetic and metabolic basis for hypoxia tolerance of hybrid fish, providing a foundation for future studies.

The novel hybrid fish BTB, derived from crossing blunt snout bream (Megalobrama amblycephala, BSB) and topmouth culter (Culter alburnus, 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 (egln3, im_7150988, znf395a, hif-1an, mknk2b, pck2, ero1a, igfbp-1a, vhl, bpifcl, egln1a, and ccna1) 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.