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Functional and comparative analysis of globin loci in pufferfish and humans

By N. (Nynke) Gillemans, T. (Tara) McMorrow, R. (Rita) Tewari, A. (Albert) Wai, C. Burgtorf, D.D. (Dubravka) Drabek, N. Ventress, A. (An) Langeveld, D. (Douglas) Higgs, K.C. Tan-Un, F.G. (Frank) Grosveld and J.N.J. (Sjaak) Philipsen

Abstract

To further our understanding of the regulation of vertebrate globin loci, we have isolated cosmids containing α- and β-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 α-globin genes (α-locus), whereas the other also contains a β-globin gene (αβ-locus). This is the first poikilothermic species analyzed in which the physical linkage of the α- and β-globin genes has been uncoupled, supporting a model in which the separation of the α- and β-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 αβ-locus suggest that a strong distal locus control region regulating the activity of the globin genes, as found in mammalian β-globin clusters, may not be present in the Fugu αβ-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

Year: 2003
DOI identifier: 10.1182/blood-2002-09-2850
OAI identifier: oai:repub.eur.nl:55271
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