Skip to main content
Log in

Evolutionary relationships among the primate Mhc-DQA1 and DQA2 alleles

  • Original Articles
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

The variation of the Mhc-DQA1 and DQA2 loci of ten different primate species (hominoids and Old World monkeys) was studied in order to obtain an insight in the processes that generate polymorphism of major histocompatibility complex (Mhc) class II genes and to establish the evolutionary relationships of their alleles. To that end nucleotide sequences of 36 Mhc class II DQA1 and seven DQA2 second exons were determined and phylogenetic trees that illustrate their evolutionary relationships were constructed. We demonstrate the existence of four primate Mhc-DQA1 allele lineages, two of which probably existed before the separation of the ancestors of the hominoids and Old World monkeys (approximately 22–28 million years ago). Mhc-DQA2 sequences were found only in the hominoid species and showed little diversity. We found no evidence for a major contribution of recombinational events to the generation of allelic diversity of the primate Mhc-DQA1 locus. Instead, our data suggest that the primate Mhc-DQA1 and DQA2 loci are relatively stable entities that mutated primarily as a result of point mutations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Andrews, P.: Fossil evidence on human origins and dispersal. Cold Spring Habor Symp Quant Biol LI: 419–428, 1986

  • Arden, B. and Klein, J.: Biochemical comparison of major histocompatibility complex molecules from different subspecies of Mus musculus: evidence for trans-specific evolution of alleles. Proc Natl Acad Sci USA 79: 2342–2346, 1982

    Google Scholar 

  • Auffray, C., Lillie, J. W., Korman, A. J., Boss, J. M., Fréchin, N., Guillemot, F., Cooper, J., Mulligan, R. C., and Strominger, J. L.: Structure and expression of HLA-DQα and -DXα genes: interallelic alternate splicing of the HLA-DQα gene and functional splicing of the HLA-DXα gene using a retroviral vector. Immunogenetics 26: 63–67, 1987

    Google Scholar 

  • Bontrop, R. E., Otting, N., Broos, L. A. M., Noort, M. C., Kenter, M., and Jonker, M.: RFLP analysis of the HLA-, ChLA- and RhLA-DQ alpha chain gene regions: conservation of restriction sites during evolution. Immunogenetics 30: 432–439, 1989

    Google Scholar 

  • Devereux, J., Haeberli, P., and Smithies, O.: A comprehensive set of sequence analysis programs for the VAX. Nucleic Acid Res 12: 387–395, 1984

    Google Scholar 

  • Fitch, W. M. and Margoliash, E.: Construction of phylogenetic trees. Science 155: 279–284, 1967

    CAS  PubMed  Google Scholar 

  • Gorski, J. and Mach, B.: Polymorphism of human Ia antigens: gene conversion between two DRβ loci results in a new HLA-D/DR specificity. Nature 322: 67–70, 1986

    Google Scholar 

  • Gyllensten, U. B. and Erlich, H. A.: Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus. Proc Natl Acad Sci USA 85: 7652–7656, 1988

    Google Scholar 

  • Gyllensten, U. B. and Erlich, H. A.: Ancient roots for polymorphism at the HLA-DQα locus in primates. Proc Natl Acad Sci USA 86: 9986–9990, 1989

    Google Scholar 

  • Helmuth, R., Fildes, N., Blake, E., Luce, M. C., Chimera, J., Madej, R., Gorodezky, C., Stoneking, M., Schmill, N., Klitz, W., Higuchi, R., and Erlich, H. A.: HLA-DQα allele and genotype frequencies in various human populations, determined by using enzymatic amplification and oligonucleotide probes. Am J Hum Genet 47: 515–523, 1990

    Google Scholar 

  • Higuchi, R., von Beroldingen, C. H., Sensabaugh, G. F., and Erlich, H. A.: DNA typing from single hairs. Nature 332: 543–546, 1988

    Google Scholar 

  • Hughes, A. L.: Testing for interlocus genetic exchange in the MHC: a reply to Andersson and co-workers. Immunogenetics 33: 243–246, 1991

    Google Scholar 

  • Hughes, A. L. and Nei, M.: Pattern of nucleotide substitutions at major histocompatibility complex class I loci reveals overdominant selection. Nature 335: 167–170, 1988

    Article  CAS  PubMed  Google Scholar 

  • Hughes, A. L. and Nei, M.: Nucleotide substitutions at major histocompatibility complex class II loci: evidence for overdominant selection. Proc Natl Acad Sci USA 86: 958–962, 1989

    CAS  PubMed  Google Scholar 

  • Jonsson, A.-K., Hyldig-Nielsen, J.-J., Servenius, B., Larhammer, D., Andersson, G., Jörgensen, F., Peterson, P. A., and Rask, L. J.: Class II genes of the human major histocompatibility complex. J Biol Chem 262: 8767–8777, 1987

    Google Scholar 

  • Jukes, T. H. and Cantor, C. R.: Evolution of proteins. In H. N. Munro (ed.): Mammalian Protein Metabolism, pp. 21–132, Academic Press, New York, 1969

    Google Scholar 

  • Kappes, D. and Strominger, J. L.: Human class II major histocompatibility complex genes and proteins. Annu Rev Biochem 57: 991–1028, 1988

    Google Scholar 

  • Kawakami, T. G., Huff, S. D., Buckley, P. M., Dungworth, D. L., and Snyder, S. P.: C-type virus associated with Gibbon lymphosarcoma. Nature New Biology 235: 170–171, 1972

    Google Scholar 

  • Klein, J. and Figueroa, F.: Evolution of the major histocompatibility complex. CRC Crit Rev Immun 6: 295–386, 1986

    Google Scholar 

  • Klein, J.: Origin of major histocompatibility complex polymorphism: the trans-species hypothesis. Hum Immunol 19: 155–162, 1987

    Article  CAS  PubMed  Google Scholar 

  • Klein, J. and Takahata, N.: The major histocompatibility complex and the quest for origins. Immunol Rev 113: 5–25, 1990

    Google Scholar 

  • Klein, J., Bontrop, R. E., Dawkins, R. L., Erlich, H. A., Gyllensten, U. B., Heise, E. R., Jones, P. P., Parham, P., Wakeland, E. K., and Watkins, D. I.: Nomenclature for the major histocompatibility complexes of different species: a proposal. Immunogenetics 31: 217–219, 1990

    CAS  PubMed  Google Scholar 

  • Koop, B. F., Goodman, M., Xu, P., Chan, K., and Slightom, J. K.: Primate η-globin DNA sequences and man's place among the great apes. Nature 319: 234–238, 1986

    Google Scholar 

  • Maniatis, T., Fritsch, E. F., Sambrook, J.: Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, 1982

    Google Scholar 

  • Okada, K., Boss, J. M., Prentice, H., Spies, T., Mengler, R., Auffray, C., Lillie, J., Grossberger, D., and Strominger, J. L.: Gene organisation of DC and DX subregions of the human major histocompatibility complex, Proc Natl Acad Sci USA 82: 3410–3414, 1985

    Google Scholar 

  • Parham, P., Lawlor, D. A., Lomen, C. E., and Ennis, P. D.: Diversity and diversification of HLA-A,B,C alleles. J Immunol 132: 3937–3950, 1989

    Google Scholar 

  • Pilbeam, D.: The descent of hominoids and hominids. Sci Am 250: 60–69, 1984

    Google Scholar 

  • Rada, C., Lorenzi, R., Powis, S. J., van den Bogaerde, J., Parham, P., and Howard, J. C.: Concerted evolution of class I genes in the major histocompatibility complex of murine rodents. Proc Natl Acad Sci USA 87: 2167–2171, 1990

    Google Scholar 

  • Saiki, R. K., Scharf, S., Faloona, F., Mullis, K. B., Horn, G. T., Erlich, H. A., and Arnheim, N.: Enzymatic amplification of β-globin genomic sequences and restriction site analysis of sickle cell anaemia. Science 230: 1350–1354, 1985

    CAS  PubMed  Google Scholar 

  • Saiki, R. K., Gelfand, D. H., Stoffel, S., Scharf, S. J., Higuchi, R., Horn, G. T., Mullis, K. B., and Erlich, H. A.: Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239: 487–491, 1988

    CAS  PubMed  Google Scholar 

  • Saiki, R. K., Walsh, P. S., Levenson, C. H., and Erlich, H. A.: Genetic analysis of amplified DNA with immobilized sequence-specific oligonucleotide probes. Proc Natl Acad Sci USA 86: 6230–6234, 1989

    Google Scholar 

  • Saitou, N. and Nei, M.: The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4: 406–425, 1987

    CAS  PubMed  Google Scholar 

  • Sanger, F., Nicklen, S., and Carlson, R.: DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 77: 5463–5467, 1977

    Google Scholar 

  • Scharf, S. J., Horn, G. T., and Erlich, H. A.: Direct cloning and sequence analysis of enzymatic amplified genomic sequences. Science 233: 1076–1078, 1986

    Google Scholar 

  • She, J. X., Boehme, S. A., Wang, T. W., Bonhomme, F., and Wakeland, E. K.: Amplification of major histocompatibility complex class II gene diversity by intraexonic recombination. Proc Natl Acad Sci USA 88: 453–457, 1991

    Google Scholar 

  • Sneath, P. H. A. and Sokal, R. R.: Numerical Taxonomy. W. H. Freeman, San Francisco, 1973

    Google Scholar 

  • Weiss, E. H., Mellor, A. L., Golden, L., Fahrner, K., Simpson, E., Hurst, J., and Flavell, R. A.: The structure of a mutant H-2 gene suggests that the generation of polymorphism in H-2 genes may occur by gene-conversion like events. Nature 301: 671–674 1983

    Google Scholar 

  • Wheeler, C. J., Maloney, D., Fogel, S., and Goodenow, R. S.: Microconversion between murine H-2 genes integrated into yeast. Nature 347: 192–194, 1990

    Google Scholar 

  • WHO Nomenclature Committee: Nomenclature for factors of the HLA system, 1989. Immunogenetics 31: 131–140, 1990

    Google Scholar 

  • Wu, S., Saunders, T. H., and Bach, F. H.: Polymorphism of human Ia antigens generated by reciprocal intergenic exchange between two DRβ loci. Nature 324: 676–679, 1986

    Google Scholar 

  • Wu, T. T. and Kabat, E. A.: An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chain and their implications for antibody complementarity. J Exp Med 132: 211–250, 1970

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession numbers M76186-M76229.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kenter, M., Otting, N., Anholts, J. et al. Evolutionary relationships among the primate Mhc-DQA1 and DQA2 alleles. Immunogenetics 36, 71–78 (1992). https://doi.org/10.1007/BF00215282

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00215282

Keywords

Navigation