Different evolutionary patterns of hypoxia-inducible factor α (HIF-α) isoforms in the basal branches of Actinopterygii and Sarcopterygii

• All three HIF-α isoforms are well preserved in basal ray-finned fish.
• The HIF-1α and -2α in amphibians and lungfish are positively selected.
• The HIF-1α and -2α are more functionally diverged in teleosts.
• The HIF-1α and -2α in different lineages exhibit different levels of activity.

Hypoxia-inducible factor (HIF) is a crucial regulator of cellular and systemic responses to low oxygen levels. Here we firstly cloned three HIF-α isoforms from the basal branches of Osteichthyes and used computational tools to characterise the molecular change underlying the functional divergence of HIF-α isoforms in different lineages. Only the HIF-1α and HIF-2α in African lungfish and amphibians were found under positive selection. HIF-1α and -2α were less functionally divergent in basal ray-finned fish than in teleosts, and showed conserved but different transcriptional activity towards specific target genes.