بیان ژن وابسته به اکسیژن در ماهی Oxygen-dependent gene expression in fishes

It now appears that fish possess homologs of HIF- and -, which may play similar roles as those in mammals in hypoxic gene expression. While ARNT had been characterized in fish in the context of pollutant stress in the 1990s (80), the sequence of first fish HIF- was reported from rainbow trout in 2001 (100). The cDNA encodes a protein of 766 amino acids and includes regions recognizable as basic-helix-loop-helix, PAS, and ODD domains of the -subunits of HIF. Moreover, proline and asparagine residues, which are the hydroxylation targets in mammals, are conserved in the rainbow trout protein. Similarity searches of the deduced amino acid sequence revealed this protein to be most similar to HIF-1 from other vertebrates. In the subsequent year, a second HIF- was cloned and sequenced from the killifish Fundulus heteroclitus (81). The deduced protein is 873 amino acids long, contains domains and specific amino acid residues thought to be functionally important, and is most similar to HIF-2 from other vertebrates. At the time of this writing, there are six fish HIFs available in the Swiss-Prot and TrEMBL databases (accession numbers Q98SW2, Q6STN7, Q8QGM4, Q6STN6, Q6EHI4 and Q6EGR9). Phylogenetic analyses show that these proteins fall into three discrete groups (Fig. 3). In addition to the deduced rainbow trout protein (Q98SW2), putative HIF-1s have been sequenced in grass carp, Ctenopharyngodon idella (Q6STN7), and zebrafish (Q6EHI4). The only fish HIF-2 described to date is from killifish (Q8QGM4). The two remaining putative HIF proteins are from grass carp (Q6STN6), and zebrafish (Q6EGR9). These proteins are equally distantly related to HIF-1 and HIF-2, and they form a distinct group in phylogenetic analyses. Interestingly, they are not very similar to mammalian HIF-3, either, making their placement in a phylogenetic tree uncertain. From the limited data available, it is unclear whether this last group of fish HIF- subunits are orthologs of mammalian HIF-3 or if they represent a distinct gene, perhaps specific to fish. Indeed, although the zebrafish protein has been named as HIF-3, the grass carp protein has tentatively been named HIF-4. More robust analyses, which include a larger number of HIF-3 and potential HIF-4 sequences from a broader distribution of fish and nonmammalian tetrapod vertebrates, will be necessary to resolve the relationship of these enigmatic HIF- subunits. HIF Stability,