Levels of oxygen can vary dramatically in aquatic environments. Aquatic organisms, including fishes, have adapted accordingly to survive. As there are both phylogenetically closely related fish species with differing oxygen requirements and distantly related species with similar oxygen requirements, fishes are good candidates for examining oxygen-related functions in vertebrates. We set out to investigate if sequence variation in the hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene is associated with variations in oxygen requirements. Since the telcost HIF-1 alpha sequences available in databases represent a very limited dataset both phylogenctically and with regard to oxygen requirements, we have sequenced the protein coding sequence for HIF-1 alpha from an additional 9 fish species. Our results indicate that the deduced HIF-1 alpha proteins of teleost fishes are somewhat shorter than those of tetrapods. Additionally, the results suggest that tetrapod sequences more closely resemble the ancestral form of the protein than do teleost sequences. No clear signatures which could be associated with the oxygen requirements of the species were found. This study suggests that if species-specific differences in HIF-1 alpha function with regards to oxygen dependence have evolved, they do not occur in the protein coding sequence but at other levels of the HIF-1 alpha pathway. (c) 2007 Elsevier Inc. All rights reserved.