Genomic Analysis of Hypoxia Inducible Factor Alpha Evolution in Ray-finned Fishes (Actinopterygii)

Two rounds of genome duplication (GD) in the ancestor of vertebrates, followed by additional GD during the evolution of ray-finned fishes (Actinopterygii), expanded certain gene families, including those encoding the hypoxia inducible transcription factor (HIF). The present study analyzed Actinopterygian genomes for duplicates of HIF, the subunit that confers oxygen-dependent gene regulation. In contrast to tetrapod vertebrates that retain three HIF genes from the ancestral vertebrate GD, four HIF forms were found in the genomes of primitive Actinopterygians (spotted gar and Asian arowana). All four forms have been retained in zebrafish and related species (Otocephala) and salmonids and their sister taxa (northern pike) but one of them (HIF4) was lost during the evolution of more derived fishes (Neoteleostei). In addition, the current analyses confirm that Otocephala retain duplicates of HIF1 and HIF2 from the teleost-specific GD, provide new evidence of salmonid-specific duplicates of HIF1, HIF2, and HIF3, and reveal a broad distribution of a truncated form of HIF2 in salmonids and Neoteleostei. This study delivers a comprehensive view of HIF evolution in the ray-finned fishes, highlights the need for a consistent nomenclature, and suggests avenues for future research on this critical transcription factor.