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Prepublished online as a Blood First Edition Paper on November 27, 2002; DOI 10.1182/blood-2002-09-2850.
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Blood, 1 April 2003, Vol. 101, No. 7, pp. 2842-2849
RED CELLS
Functional and comparative analysis of globin loci in pufferfish
and humans
Nynke Gillemans,
Tara McMorrow,
Rita Tewari,
Albert W. K. Wai,
Carola Burgtorf,
Dubravka Drabek,
Nicki Ventress,
An Langeveld,
Douglas Higgs,
Kian Tan-Un,
Frank Grosveld, and
Sjaak Philipsen
From the MGC Department of Cell Biology, Erasmus MC,
Rotterdam, The Netherlands; Department of Pharmacology,
University College Dublin, Belfield, Ireland; Department
of Biology, Imperial College of Science, Technology and Medicine,
London, United Kingdom; MPI für Molekulare Genetik,
Ihnestrasse, Berlin, Germany; MRC Molecular Haematology
Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford,
United Kingdom; and Department of Zoology, University of
Hong Kong, China.
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.
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