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 ␣-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

Oxygen Supply from the Bird's Eye Perspective

“…The position in the genome and gene synteny may provide additional information about globin evolution (33,34). In this context, LUC2L is the only informative gene (13,35).…”

Sequencing and mapping hemoglobin gene clusters in the Australian model dasyurid marsupial <i>Sminthopsis macroura</i>

“…Observations that in pufferfish the ß globin locus is closely linked to two · genes, although the · locus has no neighboring ß globin genes (Gillemans et al, 2003), provides additional support for this genome duplication theory.…”

Organization of a β and α Globin Gene Set in the Teleost Atlantic Cod, Gadus morhua

“…The direction of transcription is tail-to-tail (5 0 -3 0 , 3 0 -5 0 ) in the embryonic pair but headto-head (3 0 -5 0 , 5 0 -3 0 ) in the adult globin pair (Brownlie et al 2003). Similarly, the globin genes in pufferfish are closely linked and directed in opposite transcriptional orientations (Gillemans et al 2003). In salmon (Wagner et al 1994), the genes are oriented 5 0 -3 0 , 3 0 -5 0 (tail-to-tail orientation), similar to the zebrafish embryonic pair.…”

“…Globin gene regions have been characterized in some model fish species, such as pufferfish (Fugu rubripes, Gillemans et al 2003), embryonic and adult zebrafish (Danio rerio, Brownlie et al 2003;Chan et al 1997), and medaka (Oryzias latipes, Maruyama et al 2004), as well as in the semimodel Atlantic salmon (Salmo salar, Wagner et al 1994). In these fish, the a and b loci are a linked set and are located on the same chromosome.…”