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Journal Article

Functional and comparative analysis of globin loci in pufferfish and humans


Burgtorf,  Carola
Max Planck Society;

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Gillemans, N., McMorrow, T., Tewari, R., Wai, A. W. K., Burgtorf, C., Drabek, D., et al. (2003). Functional and comparative analysis of globin loci in pufferfish and humans. Blood, 101(7), 2842-2849. doi:10.1182/blood-2002-09-2850.

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