title: Functional and comparative analysis of globin loci in pufferfish and humans.
abstract: 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.
authors.affiliation: MGC Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Nynke
authors.initials: N
authors.lastname: Gillemans
authors.forename: Tara
authors.initials: T
authors.lastname: McMorrow
authors.forename: Rita
authors.initials: R
authors.lastname: Tewari
authors.forename: Albert W K
authors.initials: AW
authors.lastname: Wai
authors.forename: Carola
authors.initials: C
authors.lastname: Burgtorf
authors.forename: Dubravka
authors.initials: D
authors.lastname: Drabek
authors.forename: Nicki
authors.initials: N
authors.lastname: Ventress
authors.forename: An
authors.initials: A
authors.lastname: Langeveld
authors.forename: Douglas
authors.initials: D
authors.lastname: Higgs
authors.forename: Kian
authors.initials: K
authors.lastname: Tan-Un
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
authors.forename: Sjaak
authors.initials: S
authors.lastname: Philipsen
mesh_terms: D000818:Animals; D016384:Consensus Sequence; D004912:Erythrocytes; D019143:Evolution, Molecular; D020440:Gene Duplication; D005786:Gene Expression Regulation; D005914:Globins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D019901:Locus Control Region / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D005810:Multigene Family / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D023741:Takifugu / Q000235:genetics*
chemical_list: D005914:Globins