Advertisement

MHC polymorphism and parasites

  • Jan Klein
  • Colm O’huigin

Summary

The major histocompatibility complex (MHC) polymorphism is marked by the existence of allelic lineages that are extremely old, having been passed from one species to another in an evolutionary line of descent. Each species has several of these lineages and many of their more recent derivatives, the actual alleles. The lineages are separated by large genetic distances and are characterized by the presence of short sequence motifs which, at the protein level, have remained virtually unaltered for over 40 million years. Several explanations for the MHC polymorphism have been proposed. We argue that the only one consistent with the entire body of knowledge about the MHC is an explanation based on the immune response to parasites. Furthermore, we propose that parasites coevolving with their hosts have had a major influence on MHC polymorphism, whereas parasites that switched hosts recently and became very virulent have had little effect. The latter category includes micro- and macroparasites responsible for the major human infectious diseases. This hypothesis explains why no convincing association between human leucocyte antigen (HLA) alleles and resistance to infectious disease can thus far be documented, and indicates the direction in which the search for such associations should be taken.

Keywords

Major Histocompatibility Complex Cerebral Malaria Major Histocompatibility Complex Molecule Major Histocompatibility Complex Gene Major Histocompatibility Complex Allele 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Allsopp, C.E.M., Harding, R.M., Taylor, C., Bunce, M., Kwiatkowski, D., Anstey, N., Brewster, D., McMichael, A.J., Greenwood, B.M. & Hill, A.V.S. 1992 Interethnic genetic differentiation in Africa: HLA class I antigens in the Gambia. Am. J. hum. Genet. 50, 411–421.PubMedGoogle Scholar
  2. Aota, S. & Ikemura, T. 1986 Diversity in G + C content at the third position of codons in vertebrate genes and its cause. Nucl. Acids Res. 14, 6345–6355.PubMedCrossRefGoogle Scholar
  3. Brooks, D.R. & McLennan, D.A. 1993 Parascript, Parasites and the language of evolution. Washington: Smithsonian Institution Press.Google Scholar
  4. Cameron, T.W.M. 1956 Parasites and parasitism. London: Methuen & Co.Google Scholar
  5. Carter, R., Schofield, L. & Mendis, K. 1992 HLA effects in malaria: Increased parasite-killing immunity or reduced immunopathology? Parasitol. Today 8, 41–42.PubMedCrossRefGoogle Scholar
  6. Despres, L., Imbert-Establet, D., Combes, C. & Bonhomme, F. 1992 Molecular evidence linking hominoid evolution to recent radiation of schistosomes (Platyhelminthes: Trematoda). Molec. phylogenet. Evol. 1, 295–304.PubMedCrossRefGoogle Scholar
  7. Fahrenholz, H. 1913 Ectoparasiten und Abstammungslehre. Zool. Anz., Leipzig 41, 371–374.Google Scholar
  8. Germain, R.N. 1994 MHC-dependent antigen processing and peptide presentation: Providing ligands for T lymphocyte activation. Cell 76, 287–299.PubMedCrossRefGoogle Scholar
  9. Gill, T.J. III 1994 Reproductive immunology and immunogenetics. In The Physiology of reproduction (ed. E. Knobil & J. D. Neil), 2nd edn, pp. 783–812. New York: Raven Press.Google Scholar
  10. Hard, D.L. & Clark, A.G. 1989 Principles of population genetics, 2nd edn. Sunderland, Massachusetts: Sinauer.Google Scholar
  11. Hill, A.V.S., Allsopp, C.E.M., Kwiatkowski, D., Anstey, N.M., Twumasi, P., Rowe, P.A., Bennett, S., Brewster, D., McMichael, A.J. & Greenwood, B.M. 1991 Common West African HLA antigens are associated with protection from severe malaria.; Nature, Lond. 352, 595–600.CrossRefGoogle Scholar
  12. Hughes, A.L. & Nei, M. 1989 Nucleotide substitution at major histocompatibility complex class II loci: Evidence for overdominant selection. Proc. natn. Acad. Sci. U.S.A. 86, 958–962.CrossRefGoogle Scholar
  13. Johnson, R.B. 1986 Human disease and the evolution of pathogen virulence. J. theor. Biol. 122, 19–24.PubMedCrossRefGoogle Scholar
  14. Klein, J. 1986 Natural history of the major histocompatibility complex. New York: John Wiley.Google Scholar
  15. Klein, J. 1987 Origin of major histocompatibility complex polymorphism: The trans-species hypothesis. Hum. Immun. 19, 155–162.PubMedCrossRefGoogle Scholar
  16. Klein, J. 1989 Are invertebrates capable of anticipatory immune response? Scand. J. Immun. 29, 499–505.CrossRefGoogle Scholar
  17. Klein, J. 1991 Of HLA, tryps, and selection: An essay on coevolution of mhc and parasites. Hum. Immun. 30, 247–258.PubMedCrossRefGoogle Scholar
  18. Klein, J, Satta, Y, O’hUigin, C., Mayer, W.E. & Takahata, N. 1991 Evolution of the primate DRB region. In HLA 1991 (ed. T. Sasazuki), vol. 2, pp. 45–56. (Proceedings of the 11th International Histocompatibility Workshop, Yokohama, Japan.) Oxford University Press.Google Scholar
  19. Klein, J., Satta, Y., O’hUigin, C. & Takahata, N. 1993 The molecular descent of the major histocompatibility complex. A. Rev. Immun. 11, 269–295.CrossRefGoogle Scholar
  20. Lundberg, A.S. & McDevitt, H.O. 1992 Evolution of major histocompatibility complex class II allelic diversity: Direct descent in mice and humans. Proc. natn. Acad. Sci. U.S.A. 89, 6545–6549.CrossRefGoogle Scholar
  21. Marsh, S.G.E. & Bodmer, J.G. 1993 HLA class II nucleotide sequences, 1992. Immunogenetics 37, 79–94.PubMedCrossRefGoogle Scholar
  22. Martin, R.D. 1993 Primate origins: plugging the gaps. Nature, Lond. 363, 223–234.CrossRefGoogle Scholar
  23. Miller, J.F.A.P. 1992 The key role of the thymus in the body’s defense strategies. Phil. Trans. R. Soc. Lond. B 337, 105–124.CrossRefGoogle Scholar
  24. Mims, C.A. 1977 The pathogenesis of infectious disease. London: Academic Press.Google Scholar
  25. Neefjes, J J. & Momburg, F. 1993 Cell biology of antigen presentation. Curr. Opin. Immun. 5, 27–34.CrossRefGoogle Scholar
  26. Nelson, G.S. 1988 Parasitic zoonoses. In The biology of parasitism, pp. 13–41. New York: Alan R. Liss.Google Scholar
  27. Ochman, H. & Wilson, A.C. 1987 Evolution in bacteria: Evidence for a universal substitution rate in cellular genomes. J. molec. Evol. 26, 74–86.PubMedCrossRefGoogle Scholar
  28. Ochman, H. & Seiander, R.K. 1984 Evidence for clonal population structure in Escherichia coli. Proc. natn. Acad. Sci. U.S.A. 81, 198–201.CrossRefGoogle Scholar
  29. O’hUigin, C. 1994 Quantifying the degree of convergence in primate MHC-DRB genes. Immunol Rev. (In the press.)Google Scholar
  30. O’hUigin, C., Bontrop, R. & Klein, J. 1993 Nonhuman primate MHC- DRB sequences: a compilation. Immunogenetics 38, 165–183.PubMedGoogle Scholar
  31. Potts, W.K. & Wakeland, E.K. 1994 Evolution of MHC genetic diversity: A tale of incest, pestilence and sexual preference. Trends Genet. 9, 408–413.CrossRefGoogle Scholar
  32. Rammensee, H.G., Falk, K. & Rötzschke, O. 1993 MHC molecules as peptide receptors. Curr. Opin. Immun. 5, 35–44.CrossRefGoogle Scholar
  33. Rosqvist, R., Skurnik, M. & Wolf-Watz, H. 1988 Increased virulence of Yersinia pseudotuberculosis by two independent mutations. Nature, Lond. 334, 522–525.CrossRefGoogle Scholar
  34. Schwaiger, F.-W., Weyers, E., Epplen, C., Brün, J., Ruff, G., Crawford, A. & Epplen, J.T. 1993 The paradox of MHC-DRB exon/intron evolution: α-helix and β-sheet encoding regions diverge while hypervariable intronic simple repeats coevolve with β-sheet codons. J. molec. Evol. 37, 260–272.PubMedCrossRefGoogle Scholar
  35. Selander, R.K. & Levin, B.R. 1980 Genetic diversity and structure in Escherichia coli populations. Science, Wash. 210, 545–547.CrossRefGoogle Scholar
  36. Shadan, F.F. & Villarreal, L.P. 1993 Coevolution of persistently infecting small DNA viruses and their hosts linked to host-interactive regulatory domains. Proc. natn. Acad. Sci. U.S.A. 90, 4117–4121.CrossRefGoogle Scholar
  37. Soeda, E., Maruyama, T., Arrand, J.R. & Griffin, B.E. 1980 Host-dependent evolution of three papova viruses. Nature, Lond. 285, 165–167.CrossRefGoogle Scholar
  38. Stanley, S.M. 1975 A theory of evolution above the species level. Proc. natn. Acad. Sci. U.S.A. 72, 646–650.CrossRefGoogle Scholar
  39. Takahata, N. 1990 A simple genealogical structure of strongly balanced allelic lines and trans-species evolution of polymorphism. Proc. natn. Acad. Sci. U.S.A. 87, 2419–2423.CrossRefGoogle Scholar
  40. Takahata, N., Satta, Y. & Klein, J. 1994 Divergence time and population size in the lineage leading to modern humans. Theor. Popul. Biol. (In the press.)Google Scholar
  41. Tibayrenc, M., Ward, P., Moya, A. & Ayala, F.J. 1986 Natural populations of Trypanosoma cruzi, the agent of Chagas disease, have a complex multiclonal structure. Proc. natn. Acad. Sci. U.S.A. 83, 115–119.CrossRefGoogle Scholar
  42. Waters, A.P., Higgins, D.G. & McCutchan, T.F. 1993 The phylogeny of malaria: A useful study. Parasitol. Today 9, 246–252.PubMedCrossRefGoogle Scholar

Copyright information

© The Royal Society 1997

Authors and Affiliations

  • Jan Klein
    • 1
    • 2
  • Colm O’huigin
    • 1
  1. 1.Max-Planck-Institut für BiologieAbteilung ImmungenetikTübingenGermany
  2. 2.Department of Microbiology and ImmunologyUniversity of Miami School of MedicineMiamiUSA

Personalised recommendations