Meeting Abstract
Hypoxia inducible factor (HIF) transcription factor genes are known to play a key role in cellular response to low oxygen tension in a variety of organisms, and are frequently associated with adaptations to high altitude and other oxygen limited environments. The HIF gene products encode alpha (HIF-1α , HIF-2α , HIF-3α) and beta (ARNT, ARNT2, ARNTL) subunits that form functional heterodimers to regulate transcription. All HIF genes are characterized by the presence of two domains, the bHLH DNA binding domain and the oxygen sensing PAS domain. HIF-1α and HIF-2α/EPAS are additionally characterized by the presence of the HIF-C-terminal domain (HIF-CTAD). Despite their important role in oxygen sensing, very few studies have focused on the evolutionary history of the HIF gene family, with virtually no analyses outside of the vertebrate lineage. We have assessed the expansion and diversification of the HIF gene family in 39 eukaryotic genomes. We have also investigated the separate evolutionary histories, and selective pressures of each of the three domains that characterize the HIF family. Our results suggest that (1) the HIF-CTAD domain evolved de novo in the Bilaterian stem lineage, and is specific to a subset of the HIF genes, (2) the appearance of the HIF-2α/EPAS domain architecture is correlated with the evolution of closed-circulatory system endothelial vasculature, (3) the HIF transcription factor family is heavily constrained in the Vertebrate lineage, with the exception of HIF-3α and that (4) Pancrustacea have substantially divergent HIF genes.
