Functional and comparative analysis of globin loci in pufferfish and humans
To further our understanding of the regulation of vertebrate globin loci, we have isolated cosmids containing alpha- and beta-globin genes from the pufferfish Fugu rubripes. By DNA fluorescence in situ hybridization (FISH) analysis, we show that Fugu contains 2 distinct hemoglobin loci situated on separate chromosomes. One locus contains only alpha-globin genes (alpha-locus), whereas the other also contains a beta-globin gene (alpha beta-locus). This is the first poikilothermic species analyzed in which the physical linkage of the alpha- and beta-globin genes has been uncoupled, supporting a model in which the separation of the alpha- and beta-globin loci has occurred through duplication of a locus containing both types of genes. Surveys for transcription factor binding sites and DNaseI hypersensitive site mapping of the Fugu alpha beta-locus suggest that a strong distal locus control region regulating the activity of the globin genes, as found in mammalian beta-globin clusters, may not be present in the Fugu alpha beta-locus. Searching the human and mouse genome databases with the genes surrounding the pufferfish hemoglobin loci reveals that homologues of some of these genes are proximal to cytoglobin, a recently described novel member of the globin family. This provides evidence that duplication of the globin loci has occurred several times during evolution, resulting in the 5 human globin loci known to date, each encoding proteins with specific functions in specific cell types.
|Keywords||*Evolution, Molecular, Animals, Comparative Study, Consensus Sequence, Erythrocytes, Gene Duplication, Gene Expression Regulation, Globins/biosynthesis/*genetics, Humans, Locus Control Region/genetics, Mice, Mice, Transgenic, Multigene Family/*genetics, Regulatory Sequences, Nucleic Acid, Research Support, Non-U.S. Gov't, Sequence Homology, Nucleic Acid, Takifugu/*genetics|
Gillemans, N., Tan-Un, K., Philipsen, J.N.J., Grosveld, F.G., McMorrow, T., Tewari, R., … Higgs, D.. (2003). Functional and comparative analysis of globin loci in pufferfish and humans. Blood. Retrieved from http://hdl.handle.net/1765/8231