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Trans-species evolution of Mhc-DRB haplotype polymorphism in primates: Organization of DRB genes in the chimpanzee

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Abstract

The DRB region of the human major histocompatibility complex displays length polymorphism: Five major haplotypes differing in the number and type of genes they contain have been identified, each at appreciable frequency. In an attempt to determine whether this haplotype polymorphism, like the allelic polymorphism, predates the divergence of humansfrom great apes, we have worked out the organization of the DRB region of the chimpanzee Hugo using a combination of chromosome walking, pulsed-field gel electrophoresis, and sequencing. Hugo is a DRB homozygote whose single DRB haplotype is some 440 kilobases (kb) long and contains five genes. At least one and possibly two of these are pseudogenes, while three are presumably active genes. The genes are designated DRB * A0201, DRB2 * 0101, DRB3 * 0201, DRB6 * 0105, and DRB5 * 0301, and are arranged in this order on the chromosome. The DRB2 and DRB3 genes are separated by approximately 250 kb of sequence that does not seem to contain any additional DRB genes. The DRB * A0201 gene is related to the DRB1 gene of the human DR2 haplotype; the DRB2 * 0101 and DRB3 * 0201 genes are related to the DRB2 and DRB3 genes of the human DR3 haplotype, respectively; the DRB6 * 0105 and DRB5 * 0301 genes are related to the DRBVI and DRB5 genes of the human DR2 haplotype, respectively. Thus the Hugo haplotype appears to correspond to the entire human DR2 haplotype, into which a region representing a portion of the human DR3 haplotype has been inserted. Since other chimpanzees have their DRB regions organized in different ways, we conclude that, first, the chimpanzee DRB region, like the human DRB region, displays length polymorphism; second, some chimpanzee DRB haplotypes are longer than the longest known human DRB haplotypes; third, in some chimpanzee haplotypes at least, the DRB genes occur in combinations different from those of the human haplotypes; fourth, and most importantly, certain DRB gene combinations have been conserved in the evolution of chimpanzees and humans from their common ancestors. These data thus provide evidence that not only allelic but also haplotype polymorphism can be passed on from one species to another in a given evolutionary lineage.

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References

  • 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 the DR\ genes. J Biol Chem 262: 8748–8758, 1987

    Google Scholar 

  • Auffray, C., Korman, A. J., Roux-Dosseto, M., Bono, R., and Strominger, J. L.: cDNA clone for the heavy chain of the human B cell alloantigen DC1: Strong sequence homology to the HLA-DR heavy chain. Proc Natl Acad Sci USA 79: 6337–6341, 1982

    Google Scholar 

  • Auffray, C., Kuo, J., DeMars, R., and Strominger, J. L.: A minimum of four human class II α chain genes are encoded in the HLA region of chromosome 6. Nature 304: 174–177, 1983

    Google Scholar 

  • Birnboim, H. C.: A rapid alkaline extraction method for the isolation of plasmid DNA. Meth Enzymol 100: 243–255, 1983

    Google Scholar 

  • Blin, N. and Stafford, D. W.: A general method for isolation of high molecular wiight DNA from eukaryotes. Nucleic Acids Res 3: 2303–2308, 1976

    Google Scholar 

  • Böhme, J., Andersson, M., Andersson, G., Möller, E., Peterson, P. A, and Rask, L.: HLA-DR \ genes vary in number between different DR specificities whereas the number of DQ \ genes is constant. J Immunol 135: 2149–2155, 1985

    Google Scholar 

  • Bontrop, R. E., Broos, L. A. M., Pham, K., Bakas, R. M., Otting, N., and Jonker, M.: The chimpanzee major histocompatibility complex class II DR subregion contains an unexpectedly high number of beta-chain genes. Immunogenetics 32: 272–280, 1990

    Google Scholar 

  • Boss, J. M. and Strominger, J. L.: Cloning and sequence analysis of the human major histocompatibility complex gene, CD-3\. Proc Natl Acad Sci USA 81: 5199–5203, 1984

    Google Scholar 

  • Carroll, M. C., Katzman, P., Alicot, E. M., Koller, B. H., Geraghty, D. E., Orr, H. T., Strominger, J. L., and Spies, T.: Linkage map of the human major histocompatibility complex including the tumor necrosis factor genes. Proc Natl Acad Sci USA 84: 8535–8539, 1987

    Google Scholar 

  • Corell, A., Martin-Villa, J. M., Morales, P., De Juan, M. D., Varela, P., Vicario, J. L., Martinez-Laso, J., and Arnaiz-Villena, A.: Exon-2 nucleotide sequences, polymorphism, and haplotype distribution of a new HLA-DRB gene: HLA-DRB6. Mol Immunol 28: 533–543, 1991

    Google Scholar 

  • Dawkins, R. L., Christiansen, F. T., Kay, P. H., Garlepp, M., McCluskey, J., Hollingsworth, P. N., and Zilko, P. J.: Disease associations with complotypes, supratypes and haplotypes. Immunol Rev 70: 5–22, 1983

    Google Scholar 

  • Dunham, I., Sargent, C. A., Trowsdale, J., and Campbell, R. D.: Molecular mapping of the human major histocompatibility complex by pulsed-field gel electrophoresis. Proc Natl Acad Sci USA 84: 7237–7241, 1987

    Google Scholar 

  • Dupont, B. (ed.): Immunobiology of the HLA. Vols. 1& 2,, Springer, New York, 1989

    Google Scholar 

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

    Google Scholar 

  • Feinberg, A. P. and Vogelstein, B.: A technique for radiolabeling DNA restriction fragments to high specific activity. Anal Biochem 137: 6–13, 1983

    Google Scholar 

  • Figueroa, G., Günther, E., and Klein, J.: MHC polymorphism predating speciation. Nature 335: 265–267, 1988

    Google Scholar 

  • Figueroa, F., O'hUigin, C., Inoko, H., and Klein, J.: Primate DRB6 pseudogenes — clue to the evolutionary origin of the HLA-DR2 haplotype. Immunogenetics 34: 324–337, 1991

    Google Scholar 

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

    Google Scholar 

  • Gorski, J. and Mach, B.: Polymorphism of human Ia antigens: gene conversion between two DR\ loci results in a new HLA-D/DR specificity. Nature 322: 67–80, 1986

    Google Scholar 

  • Gorski, J., Rollini, P., and Mach, B.: Structural comparison of the genes of two HLA-DR supertypic groups: the loci encoding DRw52 and DRw53 are not truly allelic. Immunogenetics 25: 397–402, 1987

    Google Scholar 

  • Gorski, J., Rollini, P., Long, E., and Mach, B.: Molecular organization of the HLA-SB region of the human major histocompatibility complex and evidence for two SB \ chain genes. Proc Natl Acad Sci USA 81: 3934–3938, 1984

    Google Scholar 

  • Gorski, J., Tosi, R., Strubin, M., Rabourdin-Combe, C., and Mach, B.: Serological and immunochemical analysis of the products of a single HLA-DRα and DR\ chain gene expressed in a mouse cell line after DNA-mediated cotransformation reveals that the \ chain carries a known supertypic specificity. J Exp Med 162:105–116, 1985

    Google Scholar 

  • Grosveld, F. G., Lund, T., Murray, E. J., Mellor, A. L., Dahl, H. H. M., and Flavell, R. A.: The construction of cosmid libraries which can be used to transform eukaryotic cells. Nucleic Acids Res 10: 6715–6732, 1982

    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 

  • Hardy, D. A., Bell, J. L., Long, E. O., Lindsten, T., and McDevitt H. O.: Mapping of the class II region of the human major histocompatibility complex by pulsed-field gel electrophoresis. Nature 323: 453–455, 1986

    Google Scholar 

  • Herrmann, B. G., Barlow, D. P., and Lehrach, H.: A large inverted duplication allows homologous recombination between chromosomes heterozygous for the proximal t complex inversion. Cell 48: 813–825, 1987

    Google Scholar 

  • Jarman, A. P. and Well, R. A.: Hypervariable minisatellites: Recombinators or innocent bystanders? Trends Genet 5: 367–371, 1989

    Google Scholar 

  • Jonsson, A.-K., Andersson, L., and Rask, L.: A cellular and functional split in the DRw8 haplotype is due to a single amino acid replacement (DR\Ser57-Asp57). Immunogenetics 29: 308–316, 1989

    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 

  • Kappes, D. J., Arnot, D., Okada, K., and Strominger, J. L.: Structure and polymorphism of the HLA class II SB light chain genes. EMBO J 3: 2985–2993, 1984

    CAS  PubMed  Google Scholar 

  • Kashara, M., Klein, D., Vincek, V., Sarapata, D. E., and Klein, J.: The DRB subregion of the gorilla major histocompatibility complex: Evidence for linkage disequilibrium conserved across species. Genetics, submitted, 1992

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

    Google Scholar 

  • Klein, J.: Natural of the Major Histocompatibility Complex. Joh Wiley, New York, 1986

    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 

  • Klein, J., O'hUigin, C., Kashara, M., Vincek, V., Klein, D., and Figueora, F.: Frozen haplotypes in Mhc evolution. In J. Klein and D. Klein (eds): Molecular Evolution of the Major Histocompatibility Complex, pp 261–286, Sprimger-Verlag, Heidelberg, 1991

    Google Scholar 

  • Lawlor, D. A., Ward, F. E., Ennis, P. D., Jackson, A. P., and Parham, P.: HLA-A and -B polymorphisms predate the divergence of humans and chimpanzees. Nature 335: 268–271, 1988

    Google Scholar 

  • Lawrence, S. K., Smith, C. L., Srivastava, R., Cantor, C. R., and Weissman, S. M.: Megabase-scale mapping of the HLA gene complex by pulsed field gel electrophoresis. Science 235: 1387–1390, 1987

    Google Scholar 

  • Lee, B. S. M., Rust, N. A., McMichael, A. J., and McDevitt, H. O.: HLA-DR2 subtypes form an additional supertypic family of DRβ alleles. Proc Natl Acad Sci USA 84: 4591–4595, 1987

    Google Scholar 

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

    Google Scholar 

  • Martin, R. D.: Primate Origins and Evolution: A Phylogenetic Reconstruction. Chapman and Hall, London, 1990

    Google Scholar 

  • Mayer, W. E., Jonker, M., Klein, D., Ivanyi, P., van Seventer, G. and Klein, J.: Nucleotide sequences of chimpanzee MHC class I alleles: Evidence for trans-species mode of evolution. EMBO J 7: 2765–2774, 1988

    CAS  Google Scholar 

  • McConnell, T. J., Talbot, W. S., McIndoe, R. A., and Wakeland, E. K.: The origin of MHC class II gene polymorphism within the genus Mus. Nature 332: 651–654, 1988

    Google Scholar 

  • Messing, J.: New M13 vectors for cloning. Meth Enzymol 101: 20–77, 1983

    Google Scholar 

  • O'hUigin, C. and Klein, J.: The age and evolution of the DRB pseudogenes. In J. Klein and D. Klein (eds): Molecular Evolution of the Major Histocompatibility Complex, pp. 287–298, Springer-Verlag, Heidelberg, 1991

    Google Scholar 

  • O'hUigin, C., Bontrop, R. E., Mayer, W. E., Kupfermann, H., and Klein, J.: Nomenclature and sequences of Mhc-DRB genes from non-human primates. Immunogenetics, submitted, 1992

  • Okada, K., Prentice, H. L., Boss, J. M., Levy, D. J., Kappes, D., Spies, J. L.: SB subregion of the human major histocompatibility complex: gene organization, allelic polymorphism and expression in transformed cells. EMBO J 4: 739–748, 1985

    Google Scholar 

  • Olszweska, E. and Jones, K.: Vacuum blotting enhances nucleic acid transfer. Trends Genet 4: 92–94, 1988

    Google Scholar 

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

    Google Scholar 

  • Rollini, P., Mach, B., and Gorski, J.: Characterization of an HLA-DRβ pseudogene in the DRw52 supertypic group. Immunogenetics 25: 336–342, 1987

    Google Scholar 

  • Sanger, F., Nicklen, S., and Coulson, A. R.: DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74: 5463–5467, 1977

    CAS  PubMed  Google Scholar 

  • Servenius, B., Gustafsson, K., Widmark, E., Emmoth, E., Andersson, G., Larhammar, D., Rask, L., and Peterson, P. A.: Molecular map of the human HLA-SB (HLA-DP) region and sequence of an SBα (DPα) pseudogene. EMBO J 3: 3209–3214, 1984

    Google Scholar 

  • Sorrentino, R., Lillie, J., and Strominger, J. L.: Molecular characterization of MT 3 antigens by two-dimensional gel electrophoresis, NH2-terminal amino acid sequence analysis, and Southern blot analysis. Proc. Natl Acad Sci USA 82: 3794–3798, 1985

    Google Scholar 

  • Spielman, R. S., Lee, J., Bodmer, W. F., Bodmer, J. G., and Trowsdale, J.: Six HLA-Dα-chain genes on human chromosome 6: polymorphisms and associations of DCα-related sequences with DR types. Proc Natl Acad Sci USA 81: 3461–3465, 1984

    Google Scholar 

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

    Google Scholar 

  • Steinmetz, M., Stephan, D., Dastoornikoo, G. R., Gibb, E., and Romaniuk, R.: Methods in molecular immunology. Chromosomal walking in the major histocompatibility complex. In J. Lefkovits and B. Pernis (eds): Immunological Methods 3: 1–19, Academic Press, New York, 1985

    Google Scholar 

  • Steinmetz, M., Uematsu, Y., and Fischer Lindahl, K.: Hotspots of homologous recombination in mammalian genomes. Trends Genet 3: 7–10, 1987

    Google Scholar 

  • Stunz, L. L., Karr, R. W., and Anderson, R. A.: HLA-DRB1 and -DRB4 genes are differentially regulated at the transcriptional level. J. Immunol 143: 3081–3086, 1989

    Google Scholar 

  • Termijtelen, A., Gorski, J., Robbins, F. M., Tanigaki, N., Rosi, R., Tilanus, M. G. J., Scroeijers, W. E. M., and van Rood, J. J.: Correlation between polymorphisms at the DNA and at the protein level of DRw52 haplotypes revealed with a variety of techniques. Hum Immunol 22: 171–178, 1988

    Google Scholar 

  • Tiercy, J.-M., Gorski, J., Jeannet, M., and Mach, B.: Identification and distribution of three serologically undetected alleles of HLA-DR by oligonucleotide DNA typing analysis. Proc Natl Acad Sci USA 85: 198–202, 1988

    Google Scholar 

  • Tiercy, J.-M., Gorski, J., Bétuel, H., Freidel, A. C., Gebuhrer, L., Jeannet, M. and Mach, B.: DNA typing of DRw6 subtypes: Correlation with DRB1 and DRB3 allelic sequences by hybridization with oligonucleotide probes. Hum Immunol 24: 1–14, 1989

    Google Scholar 

  • Tiwari, J. L. and Terasaki, P. I.: HLA and Disease Associations. Springer, New York, 1985

    Google Scholar 

  • Trowsdale, J., Kelly, A., Lee, J., Carson, S., Austin, P., and Travers, P.: Linkage map of two HLA-SBβ and two HLA-SBα-related genes: An intron in one of the SBβ genes contains a processed pseudogene. Cell 38: 241–249, 1984

    Google Scholar 

  • Trowsdale, J., Ragoussis, J., and Campbell, R. D.: Map of the human MHC. Immunol Today 12: 443–446, 1991

    Google Scholar 

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

    Google Scholar 

  • WHO Committee for Factors of the HLA System: Nomenclature for factors of the HLA system 1990. Immunogenetics 33: 301–309, 1991

    Google Scholar 

  • Yanish-Perron, C., Vieira, J., and Messing, J.: Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene 33: 103–119, 1985

    Article  CAS  PubMed  Google Scholar 

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  1. Mladen Golubic

    Present address: Molecular biology/NN1, The Cleveland Clinic Foundation, 44195, Cleveland, OH, USA

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  1. Abteilung Immungenetik, Max-Planck-Institut für Biologie, 7400, Tübingen, Germany

    Uwe Brändle, Hideki Ono, Dagmar Klein, Mladen Golubic, Blazenka Grahovac & Jan Klein

  2. Department of Microbiology and Immunology, University of Miami School of Medicine, 33101, Miami, FL, USA

    Vladimir Vincek, Dagmar Klein & Jan Klein

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  1. Uwe Brändle
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  2. Hideki Ono
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  3. Vladimir Vincek
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Brändle, U., Ono, H., Vincek, V. et al. Trans-species evolution of Mhc-DRB haplotype polymorphism in primates: Organization of DRB genes in the chimpanzee. Immunogenetics 36, 39–48 (1992). https://doi.org/10.1007/BF00209291

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