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Abstract

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 FISH analysis we show that Fugu contains two distinct hemoglobin loci situated on separate chromosomes. One locus contains only -globin genes ( -locus) while the other also contains a -globin gene ( -locus). This is the first poikilothermic species analysed where 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 in close proximity 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 five human globin loci known to date, each encoding proteins with specific functions in specific cell types.