Advertisement

Gene Duplication and Haemoglobin Polymorphism

  • J. B. Clegg

Abstract

The introduction of electrophoretic techniques in the early 1950s soon led to the discovery that the haemoglobins of many animal species are polymorphic. In man the crucial discovery of haemoglobin S in the red cells of persons with sickle-cell anaemia was a striking illustration of the concept of disease at the molecular level, and it subsequently stimulated a great deal of research into the genetic aspects of the control of protein synthesis. Early ideas about the genetics of human haemoglobin were developed largely through family studies of individuals with various abnormal haemoglobins; particularly noteworthy were the findings of Smith & Torbert (1958) who established the existence of individual α-and β-chain genes, most probably on separate chromosomes. Haemoglobin variants proved to be the products of alleles of either α- or β-chain genes, and Hbs F and A2 were shown to be due to the existence of separate γ- and δ-chain genes. The determination of the amino acid sequences established considerable homologies between the α, β, γ and δ-chains and it was suggested that these could be most simply accounted for by assuming that the genes which determine them were originally derived from a common ancestral gene. Successive duplications followed by separate evolution of the resulting genes by point mutations would then give rise to the different but related genes that exist today (Ingram 1961). The very close homology of the β- and δ-chains and the fact that the two genes lie close together on the same chromosome was taken as an indication that they have existed as separate entities only recently in evolutionary history.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abramson R.K., Rucknagel D.L., Shreffler D.O. & Saave J.J. (1970) Homozygous HbJ Tongariki: Evidence for only one alpha-chain structural locus in Melanesians. Science 169, 194.CrossRefGoogle Scholar
  2. Bangham A.D. & Lehmann H. (1958) Multiple haemoglobins in the horse. Nature 181, 267.CrossRefGoogle Scholar
  3. Bernhardt D. (1964) Elektrophoretische Untersuchungen von hämoglobinen bei Ziegen, Hunden, Katen und Nerzen. Dt. TierärztebL Wschr. 71, 461.Google Scholar
  4. Braend M. (1967) Genetic variation of horse haemoglobin. Hereditas 58, 385.CrossRefGoogle Scholar
  5. Brimhall R., Hollan S., Jones R.T., Koler R.D. & Szelenyi LG. (1970) Multiple α-chain loci for human haemoglobin. Clin. Res. 18, 184.Google Scholar
  6. Clegg J.B. (1970) Horse haemoglobin polymorphism: Evidence for two linked nonallelic α-chain genes. Proc. R. Soc. B. 176, 235.CrossRefGoogle Scholar
  7. von Ehrenstein G. (1966) Translational variations in the amino acid sequence of the α-chain of rabbit haemoglobin. Cold Spring Harb. Symp. quant. Biol 31, 705.CrossRefGoogle Scholar
  8. Garrick M.D. & Huisman T.H.J. (1968) Gene duplication of the α-chain of goat haemoglobin: Evidence from a homozygous mutant. Biochim. biophys. Acta, 168, 585.CrossRefGoogle Scholar
  9. Hilse K. & Popp R.A. (1968) Gene duplication as the basis for amino acid ambiguity in the α-chain polypeptides of mouse haemoglobin. Proc. natn. Acad. Sci. 61, 930.CrossRefGoogle Scholar
  10. Huisman T.H.J., Wilson J.B. & Adams H.R. (1967) The heterogeneity of goat haemoglobin: Evidence for the existence of two non-allelic and one allelic α-chain structural genes. Arch. Biochem. 121, 528.CrossRefGoogle Scholar
  11. Huisman T.H.J., Brandt G. & Wilson J.B. (1968) The structure of goat haemoglobins. II Structural studies of the α-chains of the haemoglobins A and B. J. Biol. Chem. 243, 3675.PubMedGoogle Scholar
  12. Huisman T.H.J., Schroeder W.A., Dozy A.M., Shelton J.R., Shelton J.B., Boyd E.M. & Apell G. (1969) Evidence for multiple structural genes for the gamma chain of human foetal haemoglobin in hereditary persistence of foetal haemoglobin. Ann. N. Y. Acad. Sci. 165, 320.CrossRefGoogle Scholar
  13. Huisman T.H. J., Schroeder W.A., Stamatoyannopoulos G., Bouver N., Shelton J.R., Shelton J.B. & Apell G. (1970) Nature of foetal haemoglobin in the Greek type of hereditary persistence of foetal haemoglobin with and without concurrent β-thalassaemia. J. clin. Invest. 49, 1035.CrossRefGoogle Scholar
  14. Hutton J. J., Schweet R.S., Wolfe H.G. & Russell E.S. (1963) Haemoglobin solubility and α-chain structure in crosses between two inbred mouse strains. Science 143, 252.CrossRefGoogle Scholar
  15. Hunter T. & Munro A. (1969) Allelic variants and the amino acid sequence of the α-chain of rabbit haemoglobin. Nature 223, 1270.CrossRefGoogle Scholar
  16. Ingram V.M. (1961) Gene evolution and the haemoglobins. Nature 189, 704.CrossRefGoogle Scholar
  17. Kilmartin J.V. & Clegg J.B. (1967) Amino-acid replacements in horse haemoglobin. Nature 213, 269.CrossRefGoogle Scholar
  18. Lehmann H. & Carrell R.W. (1968) Differences between α-and β-chain mutants of human haemoglobin and between α-and β-thalassaemia. Possible duplication of the α-chain gene. Br. med. J. 4, 748.CrossRefGoogle Scholar
  19. Popp R.A. (1965) Haemoglobin variants in mice. Fedn Proc. 24, 1252.Google Scholar
  20. Popp R.A. (1867) Haemoglobins of mice: Sequence and possible ambiguity at one position of the α-chain. J. molec. Biol. 27, 9.CrossRefGoogle Scholar
  21. Popp R.A. & Amand W.S. (1960) Studies on the mouse haemoglobin locus. I. Identification of haemoglobin types and linkage of haemoglobin with albinism. J. Hered. 51, 141.CrossRefGoogle Scholar
  22. Rifkin D.B., Rifkin M.R. & Königsberg W. (1966) The presence of two major Hb components in an inbred strain of mice. Proc. natn. Acad. Sci. 55, 586.CrossRefGoogle Scholar
  23. Schroeder W.A., Huisman T.H.J., Shelton J.R., Shelton J.B., Kleihauer E.F., Dozy A.M. & Robberson B. (1968) Evidence for multiple structural genes for the β-chain of human fetal hemoglobin. Proc. natn Acad. Sci. 60, 537.CrossRefGoogle Scholar
  24. schroeder W.A., Huisman T.H.J., Shelton J.R., Shelton J.B., Apell G. & Bouver N. (1970) Heterogeneity of foetal haemoglobin in β-thalassaemia of the negro. Am. J. hum. Genet. 22, 505.PubMedPubMedCentralGoogle Scholar
  25. Smith E.W. & Torbert J.V. (1958) Study of two abnormal haemoglobins with evidence for a new genetic locus for haemoglobin formation. Bull. Johns Hopkins Hosp. 102, 38.PubMedGoogle Scholar
  26. Weisblum B., Gonano F., von Ehrenstein G. & Benzer S. (1965) A demonstration of coding degeneracy for leucine in the synthesis of protein. Proc. natn. Acad. Sci. 53CrossRefGoogle Scholar

Copyright information

© Blackwell Scientific Publications 1971

Authors and Affiliations

  • J. B. Clegg

There are no affiliations available

Personalised recommendations