Transcriptional divergence of the duplicated hypoxia-inducible factor alpha genes in zebrafish

• Zebrafish (Danio rerio) and other cyprinids have six full-length hif alpha genes.
• We studied tissue- and developmental-specific transcription of zebrafish hif alphas.
• Overall hif alpha mRNA levels were highest in the brain, eye, gill and heart.
• Previously understudied hif alpha paralogs were transcribed.
• The retention of each hif paralog pair has involved unique patterns of divergence.

Oxygen availability has been a major force in shaping the physiological evolution of animals. Under reduced oxygen availability (hypoxia) major changes in gene expression are mediated by hypoxia-inducible factors (HIF alphas). Tetrapods have three hif alpha genes, whereas zebrafish (Danio rerio) and other cyprinids have six due to a teleost lineage-specific genome duplication. We studied the transcriptional divergence of the six teleost-specific hif alphas by inspecting the tissue-specific transcription patterns in adult zebrafish and by monitoring the early developmental transcription of normoxia- and hypoxia-grown zebrafish embryos. Overall we observed the highest hif alpha mRNA levels in tissues that are important for hypoxic survival, including the brain, gill and heart. Of the paralogs that have not previously received attention (hif alpha-1A, hif alpha-2B and hif alpha-3B) especially the hif alpha-2B transcription levels suggest functional relevance. The hif alpha-1A/B paralogs that have considerable coding sequence divergence displayed more overall transcriptional divergence than the hif alpha-2A/B paralog pair. The hif alpha-2A/B paralogs that are similarly conserved in coding sequence had a divergent transcription pattern during early development. When zebrafish grown in modest hypoxia were compared to normoxia grown fish, only hif alpha-3A transcription was significantly altered. These results suggest that, in zebrafish, the evolutionary retention of each hif alpha paralog pair has involved unique patterns of coding sequence divergence, adult tissue-specific transcriptional divergence or developmental transcriptional divergence.