Globin Genes: Evolution

Abstract

Hemoglobins carry oxygen from the lungs to other tissues and are encoded by a family of globin genes that are differentially expressed during development. Defects in expression of these globin genes lead to inherited anemias called thalassemias. Other globin genes encode proteins involved in oxygen storage and other functions.

Keywords: α globin; β globin; hemoglobin; myoglobin; cytoglobin; neuroglobin; thalassemia

Figure 1.

Maps of genes and gene complexes coding for globins in humans. An approximately 200‐kb region surrounding the globin gene or gene complex is shown, with genes transcribed from left to right shown as boxes above the lines, and those transcribed in the opposite direction shown as boxes below the lines. Globin genes are hatched; genes related to the Drosophila rhomboid‐5 (rho‐5) gene (C16orf 8) (chromosome 16 open reading frame 8) and FL J22341 (hypothetical protein FL J22341) are white; and the AANAT (arylalkylamine N‐acetyltransferase) gene is cross‐hatched. These three comprise an ancient syntenic group. Chromosomal locations are given to the left of each map. CEN and TEL: centromeric and telomeric ends of each arm of the chromosomes. LCR: the distal locus control region for the globin gene complex (top map); HS‐40: the major control region for the α‐globin gene complex (second map). Regions deleted in selected β‐ and α‐thalassemia mutations are shown as the bars beneath the top and second maps respectively. HPFH‐1, HPFH‐6: hereditary persistence of fetal hemoglobin; ps: pseudogene.

Figure 2.

Model of the evolution of vertebrate globin genes. The deduced times of duplication and divergence are shown along the horizontal axis, and contemporary human globin genes or gene complexes are shown at the top. Major events in globin gene evolution are noted along the tree, and time of origin of some major vertebrate groups is indicated along the horizontal axis. Globin genes are hatched; genes related to the Drosophila rhomboid‐5 gene are white; and the AANAT gene is cross‐hatched. (Revised and redrawn from a figure in Gillemans et al., ).

Figure 3.

Similarities and differences in globin gene structure. The protein‐coding exons of the indicated genes are drawn as dark gray rectangles, and the untranslated regions of the exons are drawn as light gray rectangles. All genes are oriented with their direction of transcription from left to right. Lines are drawn to connect homologous splice junctions.

close

References

Bulger M, Bender MA, von Doorninck JH et al. (2000) Comparative structural and functional analysis of the olfactory receptor genes flanking the human and mouse β‐globin gene clusters. Proceedings of the National Academy of Sciences of the USA 97: 14560–14565.

Burmester T, Ebner B, Weich B and Hankeln T (2002) Cytoglobin: a novel globin type ubiquitously expressed in vertebrate tissues. Molecular Biology and Evolution 19: 416–421.

Flint J, Tufarelli C, Peden J et al. (2001) Comparative genome analysis delimits a chromosomal domain and identifies key regulatory elements in the alpha globin cluster. Human Molecular Genetics 10: 371–382.

Gillemans N, McMorrow T, Tewari R et al. (2003) A functional and comparative analysis of globin loci in puffer fish and man. Blood (in press).

Grosveld F, van Assendelft GB, Greaves D and Kollias G (1987) Position‐independent, high‐level expression of the human β‐globin gene in transgenic mice. Cell 51: 975–985.

Gumucio D, Shelton D, Zhu W et al. (1996) Evolutionary strategies for the elucidation of cis and trans factors that regulate the developmental switching programs of the β‐like globin genes. Molecular Phylogenetics and Evolution 5: 18–32.

Higgs D, Wood W, Jarman A et al. (1990) A major positive regulatory region located far upstream of the human α‐globin gene locus. Genes and Development 4: 1588–1601.

Kent WJ, Sugnet CW, Furey TS et al. (2002) The human genome browser at UCSC. Genome Research 12: 996–1006.

Trent III JT and Hargrove MS (2002) A ubiquitously expressed human hexacoordinate hemoglobin. Journal of Biological Chemistry 277: 19538–19545.

Waterston RH, Lindblad‐Toh K, Birney E et al. (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420: 520–562.

Further Reading

Aguileta G, Bielawski JP and Yang Z (2004) Gene conversion and functional divergence in the beta‐globin gene family. Journal of Molecular Evolution 59: 177–189.

Aguileta G, Bielawski JP and Yang Z (2006) Evolutionary rate variation among vertebrate beta globin genes: implications for dating gene family duplication events. Gene 380: 21–29.

Dickerson RE and Geis I (1983) Hemoglobin: Structure, Function, Evolution and Pathology. Menlo Park, CA: Benjamin/Cummings Publishing Company, Incorporated.

Forget BG, Higgs DR, Steinberg M and Nagel RL (2001) Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. Cambridge, UK: Cambridge University Press.

Forrester WC, Epner E, Driscoll MC et al. (1990) A deletion of the human β‐globin locus activation region causes a major alteration in chromatin structure and replication across the entire β‐globin locus. Genes and Development 4: 1637–1649.

Garry DJ, Ordway GA, Lorenz JN et al. (1998) Mice without myoglobin. Nature 395: 905–908.

Gilbert W (1978) Why genes in pieces? Nature 271: 501.

Gillemans N, McMorrow T, Tewari R et al. (2003) Functional and comparative analysis of globin loci in pufferfish and humans. Blood 101: 2842–2849.

Godecke A, Flogel U, Zanger K et al. (1999) Disruption of myoglobin in mice induces multiple compensatory mechanisms. Proceedings of the National Academy of Sciences of the USA 96: 10495–10500.

Hardison R (1998) Hemoglobins from bacteria to man: evolution of different patterns of gene expression. Journal of Experimental Biology 201: 1099–1117.

Hardison R and Miller W (1993) Use of long sequence alignments to study the evolution and regulation of mammalian globin gene clusters. Molecular Biology and Evolution 10: 73–102.

Hardison R, Slightom JL, Gumucio DL et al. (1997) Locus control regions of mammalian β‐globin gene clusters: combining phylogenetic analyses and experimental results to gain functional insights. Gene 205: 73–94.

Hardison RC, Chui DHK, Giardine B et al. (2001) HbVar: a relational database of human hemoglobin variants and thalassemia mutations at the Globin Gene Server. Human Mutation 19: 225–233.

Ingram VM (1956) A specific chemical difference between globins of normal human and sickle‐cell anemia hemoglobin. Nature 178: 792.

Johnson RM, Prychitko T, Gumucio D et al. (2006) Phylogenetic comparisons suggest that distance from the locus control region guides developmental expression of primate beta‐globin genes. Proceedings of the National Academy of Sciences of the USA 103: 3186–3191.

Lam KW and Jeffreys AJ (2006) Processes of copy‐number change in human DNA: the dynamics of a‐globin gene deletion. Proceedings of the National Academy of Sciences of the USA 103: 8921–8927.

Lam KW and Jeffreys AJ (2007) Processes of de novo duplication of human a‐globin genes. Proceedings of the National Academy of Sciences of the USA 104: 10950–10955.

Vinogradov SN, Hoogewijs D, Bailly X et al. (2006) A phylogenomic profile of globins. BMC Evolutionary Biology 6: 31.

Web Links

AANAT (arylalkylamine N‐acetyltransferase); LocusID: 15. Locus Link: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=15

AANAT (arylalkylamine N‐acetyltransferase); MIM number: 600950. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?600950

CYGB (cytoglobin); LocusID: 114757. Locus Link: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=114757

Globin Gene Server. The function of DNA sequences, especially those involved in production of hemoglobin http://globin.cse.psu.edu

HBB (hemoglobin, beta); LocusID: 3043. Locus Link: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3043

HBB (hemoglobin, beta); MIM number: 141900. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?141900

MB (myoglobin); LocusID: 4151. Locus Link: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4151

MB (myoglobin); MIM number: 160000. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?160000

NGB (neuroglobin); LocusID: 58157. Locus Link: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=58157

NGB (neuroglobin); MIM number: 605304. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?605304

UCSC Genome Bioinformatics. Genome browser http://genome.ucsc.edu

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Hardison, Ross C(Apr 2008) Globin Genes: Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005134.pub2]