Chronic hypoxia induces alternative splicing of transcripts in the goldfish brain.

Several species evolved mechanisms to tolerate periods of severe environmental hypoxia and anoxia. Among them, goldfish are unique as they do not enter a comatose state under such conditions. Taking advantage of the recently published and annotated goldfish genome, we had previously profiled the transcriptomic response of the goldfish brain under normoxic (21 kPa oxygen saturation, N) and hypoxic conditions (2.1 kPa oxygen saturation) after 1 and 4 weeks (1WH, 4WH). Using the RNA-Seq data, we report the occurrence of alternative mRNA splicing (skipped exon, retained intron, alternative 3' or 5' splice sites, and mutually exclusive exons). At 1WH/N, 1004 significant alternative splicing events on 769 gene loci were identified, increasing to 1187 on 963 loci at 4WH/N. There were 305 loci with alternatively spliced transcripts common to both 1WH/N and 4WH/N, 221 of which exhibited the same precise location and splicing mechanism. Specific gene transcripts affected by alternative splicing events were almost entirely different from previously identified differentially expressed genes under chronic hypoxia. GO-term enrichment analyses of gene loci of alternatively spliced transcripts, however, did include similar pathways as previously identified for DEGs. These include epigenetic machinery, ion channel activity (1WH/N), glutamate signaling (4WH/N), endothelial cell function, and ATP hydrolyzation pathways (1WH/N + 4WH/N). We describe selected examples of alternatively spliced transcripts to discuss possible functional relevance in the goldfish brain response to chronic hypoxia. Together, our data identified an additional layer of regulation in brain pathways relevant to hypoxia tolerance in goldfish, which complement previously reported gene expression changes.