SpringerLink
Log in

Evolutionary relationship between human major histocompatibility complexHLA-DR haplotypes

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

Abstract

HLA-DR haplotypes of the human major histocompatibility complex are organized in five different groups. They can be identified based on the serological specificity expressed by the polymorphicDRB1 locus and by the presence of a characteristic set ofDRB genes. The nucleotide sequences of introns 4 and 5 of the twoDRB genes (DRB1 *01 andDRB6 *01) from aDR1 haplotype and the threeDRB genes (DRB1 *15, DRB6*15, andDRB5 *15), from aDR51 haplotype were determined. This study identified endogenous retrovial long terminal repeat elements (ERV9 LTR) located at identical positions in intron 5 of theDRB1 genes in both theDR1 andDR51 haplotypes. Phylogenetic analyses revealed a close evolutionary relationship between these two haplotypes. TheDRB5 gene, unique for theDR51 haplotype, may have been lost by a recent gene deletion event creating theDR1 haplotype. A model for the evolution of the humanDR haplotypes involving separate duplication and contraction events is presented.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Allen, M., Saldeen, T., and Gyllensten, U. B. Allele-specificHLA-DRB1 amplification of forensic evidence samples with mixed genotypes.Biotechniques 19: 454–463, 1995

    PubMed  CAS  Google Scholar 

  • Andersson, G., Larhammar, D., Widmark, E., Servenius, B., Peterson, P. A., and Rask, L. Class II genes of the human major histocompatibility complex: organization and evolutionary relationship of theDRβ genes.J Biol Chem 262: 8748–8758, 1987

    PubMed  CAS  Google Scholar 

  • Andersson, G., Lindblom, B., Andersson, L., Gorski, J., Mach, B., and Rask, L. The singleDRβ gene of theDRw8 haplotype is closely related to theDRβ3III gene encodingDRw52.Immunogenetics 28 1–5, 1988

    Article  PubMed  CAS  Google Scholar 

  • Andersson, G., Andersson, L., Larhammar, D., and Rask, L. Organization and evolution of theHLA-DRB genes.In J. Klein and D. Klein (eds.).Molecular Evolution of the Major Histocompatibility Complex, pp. 299–311, Springer, Heidelberg Berlin New York, 1991

    Google Scholar 

  • Andersson, G., Andersson, L., Larhammar, D., Rask, L., and Sigurdardóttir, S. Simplifying genetic locus assignment ofHLA-DRB genes.Immunol Today 15: 58–62, 1994

    Article  PubMed  CAS  Google Scholar 

  • Arvidsson, A.-K., Svensson, A.-C., Widmark, E., Andersson, G., Rask, L., and Larhammar, D. Characterization of three separated exons in theHLA class IIDR region of the human major histocompatibility complex.Hum Immunol 42: 254–264, 1995

    Article  PubMed  CAS  Google Scholar 

  • Ausubel, F. M., Brent, R., Kingston, R. E., Moore, D. D., Seidman, J. G., Smith, J. A., and Struhl, K. (eds.):Current Protocols in Molecular Biology, ch. 1.7.1-1.7.15, 15.0.1-15.2.11, John Wiley & Sons, New York, 1987–1994

    Google Scholar 

  • Batzer, M. A., Kilroy, G. E., Richard, P. E., Shaikh, T. H., Desselle T. D., Hoppens, C. L., and Deininger, P. L. Structure and variability of recently insertedAlu family members.Nucleic Acids Res 18: 6793–6798, 1990

    PubMed  CAS  Google Scholar 

  • Batzer, M. A., Stoneking, M., Alegria-Hartman, M., Bazan, H., Kass, D. H., Shaikh, T. H., Novick, G. E., Ioannou, P. A., Scheer, W. D., Herrera, R. J., and Deininger, P. L. African origin of human-specific polymorphicAlu insertions.Proc Natl Acad Sci USA 91: 12288–12292, 1994

    Article  PubMed  CAS  Google Scholar 

  • Bodmer, J. G., Marsh, S. G. E., Albert, E. D., Bodmer, W. F., Dupont, B., Erlich, H. A., Mach, B., Mayr, W. R., Parham, P., Sasazuki, T., Schreuder, G. M. Th., Strominger, J. L., Svejgaard, A., and Terasaki, P. I. Nomenclature for factors of theHLA system, 1994.Tissue Antigens 44: 1–18, 1994

    Article  PubMed  CAS  Google Scholar 

  • Böhme, J., Andersson, M., Andersson, G., Möller, E., Peterson, P. A., and Rask, L.HLA DRβ genes vary in number between differentDR specificites, whereas the number ofDQβ genes in constant.J Immunol 135: 2149–2155, 1985

    PubMed  Google Scholar 

  • Brändle, U., Ono, H., Vincek, V., Klein, D., Golubic, M., Grahovac, B., and Klein, J. Trans-species evolution ofMhc-DRB haplotype polymorphism in primates: organization ofDRB genes in the chimpanzee.Immunogenetics 36: 39–48, 1992

    Article  PubMed  Google Scholar 

  • Corell, A., Morales, P., Varela, P., Paz-Artal, E., Martin-Villa, J. M., Martinez-Laso, J., and Arnaiz-Villena, A. Allelic diversity at the primate major histocompatibility complexDRB6 locus.Immunogenetics 36: 33–38, 1992

    Article  PubMed  CAS  Google Scholar 

  • Dangel, A. W., Mendoza, A. R., Baker, B. J., Daniel, C. M., Carroll, M. C., Wu, L.-C., and Yu, C. Y. The dichotomous size variation of human complementC4 genes is mediated by a novel family of endogenous retroviruses, which also establishes species-specific genomic patterns among Old World primates.Immunogenetics 40: 425–436, 1994

    Article  PubMed  CAS  Google Scholar 

  • Fan, W., Kasahara, M., Gutknecht, J., Klein D., Mayer, W. E., Jonker, M., and Klein, J. Shared class II MHC polymorphisms between humans and chimpanzees.Hum Immunol 26: 107–121, 1989

    Article  PubMed  CAS  Google Scholar 

  • Figueroa, F., O'hUigin, C., Inoko, H., and Klein, J. PrimateDRB pseudogenes-clue to the evolutionary origin of theHLA-DR2 haplotype.Immunogenetics 34: 324–337, 1991

    Article  PubMed  CAS  Google Scholar 

  • Figueroa, F., O'hUigin, C., Tichy, H., and Klein, J. The origin of the primateMhc-DRB genes and allelic lineages as deduced from the study of prosiminas.J Immunol 152: 4455–4465, 1994

    PubMed  CAS  Google Scholar 

  • Gorski, J., Rollini, P., and Mach, B. Structural comparison of the genes of twoHLA-DR supertypic groups: the loci encodingDRw52 andDRw53 are not truly allelic.Immunogenetics 25: 397–402, 1987

    Article  PubMed  CAS  Google Scholar 

  • Gorski, J. TheHLA-DRw8 lineage was generated by a deletion in theDRB region followed by first domain diversification.J Immunol 142: 4041–4045, 1989

    PubMed  CAS  Google Scholar 

  • Grahovac, B., Mayer, W., Vincek, V., Figueroa, F., O'hUigin, C., Tichy, H., and Klein, J. Major histocompatibility complexDRB genes of a new world monkey, the cotton-top tamarin (Saguinus oedipus).mol Biol Evol 9: 403–416, 1992

    PubMed  CAS  Google Scholar 

  • Gyllensten, U. B., Sundvall, M., Ezcurra, I., and Erlich, H. A. Genetic diversity at class IIDRB loci of the primate major histocompatibility complex.J Immunol 146: 4368–4376, 1991

    PubMed  CAS  Google Scholar 

  • Gyllensten, U. B., and Erlich, H. A.MHC class II haplotypes and linkage disequilibrium in primates.Hum Immunol 36: 1–10, 1993

    Article  PubMed  CAS  Google Scholar 

  • Haas, D., Boss, J. M., Strominger, J. L., and Spies, T. A highly diverged β1 exon in theDR region of the humanMHC: sequence and evolutionary implications.Immunogenetics 25: 15–23, 1987

    Article  PubMed  CAS  Google Scholar 

  • Higgins, D. G., and Sharp, P. M. CLUSTAL: A package for performing multiple sequence alignments on a microcomputer.Gene 73: 237–244, 1988

    Article  PubMed  CAS  Google Scholar 

  • Higgins, D. G. and Sharp, P. M. Fast and sensitive multiple sequence alignments on a microcomputer.CABIOS 5: 151–153, 1989

    PubMed  CAS  Google Scholar 

  • Higuchi, R. Rapid efficient DNA extraction for PCR from cells or blood.Amplifications Perkin Elmer Cetus 2: 1–3, 1989

    Google Scholar 

  • Ish-Horowicz, D. and Burke, J. F. Rapid and efficient cosmid cloning.Nucleic Acids Res 9: 2989–2998, 1981

    PubMed  CAS  Google Scholar 

  • Jonsson, A.-K., Andersson, L., and Rask, L. A cellular and functional split in theDRw8 haplotype is due to a single amino acid replacement (DRβ ser 57-asp 57).Immunogenetics 29: 308–316, 1989

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  • Kambhu, S., Falldorf, P., and Lee, J. S. Endogenous retroviral long terminal repeats within theHLA-DQ locus.Proc. Natl Acad Sci USA 87: 4927–4931, 1990

    Article  PubMed  CAS  Google Scholar 

  • Kasahara, M., Klein, D., Vincek, V., Sarapata, D. E., and Klein, J. Comparative anatomy of the primate major histocompatibility complexDR subregion: evidence for combinations ofDRB genes conserved across species.Genomics 14: 340–349, 1992

    Article  PubMed  CAS  Google Scholar 

  • Kawai, J., Ando, A., Sato, T., Nakatsuji, T., Tsuji, K., and Inoko, H. Analysis of gene structure and antigen determinants of DR2 antigens usingDR gene transfer into mouse L cells.J Immunol 142: 312–317, 1989

    PubMed  CAS  Google Scholar 

  • Klein, J., O'hUigin, C., Kasahara, M., Vincek, V., Klein, D., and Figueroa, F. Frozen haplotypes inmhc evolution.In J. Klein and D. Klein (eds.),Molecular Evolution of the Major Histocompatibility Complex, pp. 261–286, Springer, Heidelberg Berlin New York, 1991

    Google Scholar 

  • Klein, J., O'hUigin, C., Figueroa, F., Mayer, W. E., and Klein, D. Different modes ofMhc evolution in primates.Mol Biol Evol 10: 48–59, 1993

    PubMed  CAS  Google Scholar 

  • Kumar, S., Tamura, K., and Nei, M.MEGA: Molecular Evolutionary Genetics Analysis, Version 1.01, The Pennsylvania State University, University Park, 1993

    Google Scholar 

  • La Mantia, G., Pengue, G., Maglione, D., Pannuti, A., Pascucci, A., and Lania, L. Identification of new human repetitive sequences: characterization of the corresponding cDNAs and their expression in embryonal carcinoma cells.Nucleic Acids Res 17: 5913–5922, 1989

    PubMed  Google Scholar 

  • Lania, L., Di Cristofano, A., Strazzullo, M., Pengue, G., Majello, B., and La Mantia, G. Structural and functional organization of human endogenous retroviralERV9 sequences.Virology 191: 464–468, 1992

    Article  PubMed  CAS  Google Scholar 

  • Larhammar, D., Servenius, B., Rask, L., and Peterson, P. A. Characterization of anHLA-DRβ pseudogene.Proc Natl Acad Sci USA 82: 1475–1479, 1985

    Article  PubMed  CAS  Google Scholar 

  • Lock, C. B., So, A. K. L., Welsh, K. I., Petkes, J. D.MHC class II sequences of an HLA-DR2 narcoleptic.Immunogenetics 27: 449–455, 1988

    Article  PubMed  CAS  Google Scholar 

  • Martin, R. D. Primate origins: plugging the gaps.Nature 363: 223–234, 1993

    Article  PubMed  CAS  Google Scholar 

  • Mñuková-Fajdelová, M., Satta, Y., O'hUigin, C., Mayer, W. E., Figueroa, F., and Klein, J.Alu elements of the primate major histocompatibility complex.Mammalian Genome 5: 405–415, 1994

    Article  PubMed  Google Scholar 

  • Rollini, P., Mach, B., and Gorski, J. Linkage map of threeHLA-DRβ-chain genes: evidence for a recent duplication event.Proc Natl Acad Sci USA 82: 7197–7201, 1985

    Article  PubMed  CAS  Google Scholar 

  • Rollini, P., Mach, B., and Groski, J. Characterization of anHLA-DRβ pseudogene in theDRw62 supertypic group.Immunogenetics 25: 336–342, 1987

    Article  PubMed  CAS  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

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Schönbach, C., Vincek, V., Mayer, W. E., Golubic, M., O'hUigin, C., and Klein, J. Multiplication ofMhc-DRB5 loci in the orangutan: implications for the evolution ofDRB haplotypes.Mammalian Genome 4: 159–170, 1993

    Article  PubMed  Google Scholar 

  • Spies, T., Sorrentino, R., Boss, J., Okada, K., and Strominger, J. L. Structural organization of theDR subregion of the human major histocompatibility complex.Proc Natl Acad Sci USA 82: 5165–5169, 1985

    Article  PubMed  CAS  Google Scholar 

  • Staden, R. An interactive graphics program for comparing and aligning nucleic acid and amino acid sequences.Nucleic Acids Res 10: 2951–2961, 1982

    PubMed  CAS  Google Scholar 

  • Svensson, A.-C., Setterblad, N., Sigurdardóttir, S., Rask, L., and Andersson, G. PrimateDRB genes from theDR3 andDR8 haplotypes containERV9 LTR elements at identical positions.Immunogenetics 41: 74–82, 1995

    Article  PubMed  CAS  Google Scholar 

  • Titus-Trachtenberg, E. A. Rickards, O., De Steano, G. F., and Erlich, H. A. Analysis ofHLA class II haplotypes in the Cayapa indians of Ecuador: a novelDRB1 allele reveals evidence for convergent evolution and balancing selection.Am J Hum Genet 55: 160–167, 1994

    PubMed  CAS  Google Scholar 

  • Trowsdale, J. “Both man & bird & beast”: comparative organization of MHC genes.Immunogenetics 41: 1–17, 1995

    Article  PubMed  CAS  Google Scholar 

  • Vineck, V., Klein, D., Figueroa, F., Hauptfeld, V., Kasahara, M., O'hUigin, C., Mach, B., and Klein, J. The evolutionary origin of theHLA-DR3 haplotype.Immunogenetics 35: 263–271, 1992

    Article  Google Scholar 

  • Wilkinson, D. A., Mager, D. L., and Leong, J.-A. C. Endogenous human retroviruses.In J. Levy (ed.):The Retroviridae (Vol. 3), pp. 465–535, Plenum Press, New York, 1994

    Google Scholar 

  • Zhu, Z. B., Hsieh, S.-L., Bentley, D. R., Campbell, R. D., and Volanakis, J. E. A variable number of tandem repeats locus within the human complement C2 gene is associated with a retroposon derived from a human endogenous retrovirus.J Exp Med 175: 1783–1787, 1992

    Article  PubMed  CAS  Google Scholar 

  • Zucchi, I. and Schlessinger, D. Distribution of moderately repetitive sequences pTR5 and LF1 in Xq24–q28 human DNA and their use in assembling YAC contigs.Genomics 12: 264–275, 1992

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Uppsala Genetic Center, Department of Cell Research, Swedish University of Agricultural Sciences, Box 7055, S-750 07, Uppsala, Sweden

    Ann-Cathrin Svensson, Niclas Setterblad, Ulla Pihlgren, Lars Rask & Göran Andersson

Authors
  1. Ann-Cathrin Svensson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Niclas Setterblad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ulla Pihlgren
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lars Rask
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Göran Andersson
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

The nucleotide sequence data reported in this paper have been submitted to the EMBL nucleotide sequence database and have been assigned the accession numbers X88791-X88794

Rights and permissions

Reprints and permissions

About this article

Cite this article

Svensson, AC., Setterblad, N., Pihlgren, U. et al. Evolutionary relationship between human major histocompatibility complexHLA-DR haplotypes. Immunogenetics 43, 304–314 (1996). https://doi.org/10.1007/BF02440998

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02440998

Keywords

Search

Navigation