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Structure and organization of pigMHC class IIDRB genes: evidence for genetic exchange between loci

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Abstract

The pig major histocompatibility complexDRB genes were studied by polymerase chain reaction (PCR) amplification of exon 2 from eight domestic pigs and two European wild boars. Sequence comparisons together with a phylogenetic analysis showed the existence of at least threeDRB genes of which only one appears to be expressed. The two putativeDRB pseudogenes contained delections in exon 2, making it possible to confirm the presence of three non-allelicDRB genes by analyzing the length polymorphism of the amplified PCR products. The expressed gene shows allelic polymorphism at the same positions as in the humanDRB1 gene. In addition this pig gene shows extensive allelic polymorphism at positions 84–88, whereas, e.g., humanDRB genes do not. Surprisingly, the the two putativeDRB pseudogenes also display a considerable amount of allelic polymorphism, albeit of a different character as compared with the expressedDRB gene. Short stretches of sequences are shared between individual alleles at different loci. These sequence similarities cannot be due to natural selection, since two of the threeDRB genes involved are polymorphic pseudogenes constituting allelic series that have diverged after the inactivation event. Instead, the results indicate that the sequences have been exchanged between theDRB genes by intergenic recombination.

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References

  • Andersson, L., Böhme, J., Peterson, P. A., and Rask, L. Genomic hybridization of bovine class II major histocompatibility genes: 2. Polymorphism ofDR genes and linkage disequilibrium in theDQDR region.Anim Genet 7: 295–304, 1986

    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 theDRB genes.J Biol Chem 262: 8748–8758, 1987

    PubMed  CAS  Google Scholar 

  • Andersson, L., Sigurdardottir, S., Borsch, C., and Gustafsson, K. Evolution of MHC polymorphism: extensive sharing of polymorphic sequence motifs between human and bovineDRB alleles.Immunogenetics 33: 188–193, 1991

    Article  PubMed  CAS  Google Scholar 

  • Andersson, L. and Mikko, S. Generation of MHC class II deversity by intra-and intergenic recombination.Immunol Rev 143: 5–12, 1995

    Article  PubMed  CAS  Google Scholar 

  • Bach, F. H., Dalmasso, A. P., and Platt, J. L. Xenotransplantation: a current perspective.Transplant Rev 6: 163–174, 1992

    Article  Google Scholar 

  • Bodmer, J. G., Marsh, S. G. E., Albert, E. D., Bodmer, W. F., Dupont, B., Ehrlich, 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 the HLA system, 1994.Tissue Antigens 44: 1–18, 1994

    Article  PubMed  CAS  Google Scholar 

  • Brown, J. H., Jardetzky, T. S., Gorga, J. C., Stern, L. J., Urban, R. G., Strominger, J. L., and Wiley, D. C. Three-dimensional structure of the human class II histocompatibility antigenHLA-DR1.Nature 364: 33–39, 1993

    Article  PubMed  CAS  Google Scholar 

  • Brunsberg, U., Gustafsson, K., Jansson, L., Michaelsson, E., Ährlund-Richter, L., Pettersson, S., Mattsson, R., and Holmdahl, R. Expression of a transgenic class IIAb gene confers susceptibility to collagen-induced arthritis.Eur J Immunol 24: 1698–1702, 1994

    Article  PubMed  CAS  Google Scholar 

  • Chomczynski, P. and Sacchi, N. Single-step method of RNA isolation by acid guanidinium thiocyanate phenol chloroform extraction.Anal Biochem 162: 156–159, 1987

    Article  PubMed  CAS  Google Scholar 

  • Denaro, M., Hammerling, U., Rask, L., and Peterson, P. A. TheE bβ gene may have acted as a donor gene in a gene conversion-like event generating theA bm12β mutant.EMBO J 3: 3745–3753, 1984

    Google Scholar 

  • Felsenstein, J. PHYLIP—Phylogeny Inference Package (version 3.2).Cladistics 5: 164–166, 1989

    Google Scholar 

  • Gianello, P., Fishbein, J. M., and Sachs, D. H. Tolerance to primarily vascularized allografts in minature swine.Immunol Rev 133: 19–44, 1993

    Article  PubMed  CAS  Google Scholar 

  • Gorski, J. and Mach, B. Polymorphism of human Ia antigens: gene conversion between two DR β loci results in a newHLA-D/DR specificity.Nature 322: 67–69, 1986

    Article  PubMed  CAS  Google Scholar 

  • Groenen, M. A. M., van der Pool, J. J., Dijkhof, R. J. M., and Giphart, M. J. The nucleotide sequence of bovine MHC class IIDQB andDRB genes.Immunogenetics 31: 37–44, 1990

    Article  PubMed  CAS  Google Scholar 

  • Gustafsson, K., Germana, S., Hirsch, F., Pratt, K., LeGuern, C., and Sachs, D. H. Structure of miniature swine class IIDRB genes: conservation of hyper-variable amino acid residues between distantly related species.Proc Natl Acad Sci USA 87: 9798–9802, 1990a

    Article  PubMed  CAS  Google Scholar 

  • Gustafsson, K., LeGuern, C., Hirsch, F., Germana, S., Pratt, K., and Sachs, D. H. Class II genes of miniature swine: IV. Characterization and expression of two allelic class IIDQB cDNA clones.J Immunol 145: 1946–1951, 1990b

    PubMed  CAS  Google Scholar 

  • Gustafsson, K., Karlsson, M., Andersson, L., and Holmdahl, R. Structures on theI-A molecule predisposing for susceptibility to type II collagen induced autoimmune arthritis.Eur J Immunol 20: 2127–2131, 1990c

    Article  PubMed  CAS  Google Scholar 

  • Gustafsson, K., Brunsberg, U., Sigurdardottir, S., and Andersson, L. A phylogenetic investigation of MHC class IIDRB genes reveals convergent evolution in the antigen binding site.In J. Klein and D. Klein (eds.):NATO ASI Series, vol. H59, Molecular Evolution of the Major Histocompatibility Complex, pp. 119–130, Springer Verlag, Berlin Heidelberg, 1991

    Google Scholar 

  • Gustafsson, K. and Andersson, L. Structure and polymorphism of horse MHC class IIDRB genes: convergent evolution in the antigen binding site.Immunogenetics 39: 355–358, 1994

    Article  PubMed  CAS  Google Scholar 

  • Gyllensten, U. B., Sundvall, M., and Ehrlich, H. A. Allelic diversity is generated by intraexon sequence exchange at theDRB1 locus of primates.Proc Natl Acad Sci USA 88: 3686–3690, 1991

    Article  PubMed  CAS  Google Scholar 

  • Hirsch, F., Sachs, D. H., Gustafsson, K., Pratt, K., Germana, S., and LeGuern, C. Class II genes of miniature swine: III. Characterization of an expressed pig class II gene homologous toHLA-DQA.Immunogenetics 31: 52–56, 1990

    Article  PubMed  CAS  Google Scholar 

  • Hirsch, F., Germana, S., Gustafsson, K., Pratt, K., Sachs, D. H., and LeGuern, C. Structure and expression of class II α genes in miniature swine.J Immunol 149: 841–846

  • Holmdahl, R., Karlsson, M., Andersson, M. E., Rask, L., and Andersson, L. Localization of a critical restriction site on theI-A beta chain which determines susceptibility to collagen induced arthritis.Proc Natl Acad Sci USA 86: 9475–9479, 1989

    Article  PubMed  CAS  Google Scholar 

  • Johansson, M., Ellegren, H., Marklund, L., Gustavsson, U., Ringmar-Cederberg, E., Andersson, K., Edfors-Lilja, I., and Andersson, L. The gene for dominant white color in the pig is closely linked toALB andPDGFRA on chromosome 8.Genomics 14: 965–969, 1992

    Article  PubMed  CAS  Google Scholar 

  • Kimura, M. A simple method for estimating evolutionary rate of base substitutions through comparative studies of nucleotide sequences.J Mol Evol 16: 111–117, 1980

    Article  PubMed  CAS  Google Scholar 

  • Klein, J.Natural History of the Major Histocompatibility Complex, John Wiley & Sons, New York, 1986

    Google Scholar 

  • Klein, J., Satta, Y., and O'hUigin, C. The molecular descent of the major histocompatibility complex.Annu Rev Immunol 11: 269–295, 1993

    Article  PubMed  CAS  Google Scholar 

  • Klein, J. and O'hUigin, C. Class IIBMhc motifs in an evolutionary perspective.Immunol Rev 143: 89–111, 1995

    Article  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, PA, 1993

    Google Scholar 

  • Marsh, S. G. E. and Bodmer, J. G. HLA class II nucleotide sequences, 1992.Eur J Immunogenet 20: 47–79, 1993

    Article  PubMed  CAS  Google Scholar 

  • O'hUigin, C. Quantifying the degree of convergence in primateMhc-DRB genes.Immunol Rev 143, 123–140, 1995

    Article  PubMed  Google Scholar 

  • Pääbo, S., Irwin, D. M., and Wilson, A. C. DNA damage promotes jumping between templates during enzymatic amplification.J Biol Chem 265: 4718–4721, 1990

    PubMed  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 

  • Sarmiento, U. M., Sarmiento, J. I., and Storb, R. Allelic variation in theDR subregion of the canine major histocompatibility complex.Immunogenetics 32: 13–19, 1990

    Article  PubMed  CAS  Google Scholar 

  • Shia, Y.-C., Bradshaw, M., Rutherford, M. S., Lewin, H. A., and Schook, L. B. Polymerase chain reaction based genotyping for characterisation ofSLA-DQB andSLA-DRB alleles in domestic pigs.Anim Genet 26: 91–100, 1995

    Article  PubMed  CAS  Google Scholar 

  • Sigurdadottir, S., Borsch, C., Gustafsson, K., and Andersson, L. The exon encoding the antigen recognition site of class II β-chains is divided into two subregions with different evolutionary histories.J Immunol 148: 968–973, 1992

    Google Scholar 

  • Takahata, N. MHC diversity and selection.Immunol Rev 143: 225–247, 1995

    Article  PubMed  CAS  Google Scholar 

  • Tonnelle, C., De Mars, R., and Long, E. O.DOβ: a new β chain gene inHLA-D with a distinct regulation of expression.EMBO J 4: 2839–2847, 1985

    PubMed  CAS  Google Scholar 

  • Våge, D. I., Olsaker, I., Lingaas, F., and Lie, Ø. Isolation and sequence determination of porcine class IIDRB alleles amplified by the polymerase chain reaction (PCR).Anim Genet 25: 73–75, 1994

    PubMed  Google Scholar 

  • Wakeland, E. K., Boehme, S., and She, J. X. The generation and maintenance of MHC class II gene polymorphism in rodents.Immunol Rev 113: 207–226, 1990

    Article  PubMed  CAS  Google Scholar 

  • Walsh, J. B. Sequence-dependent gene conversion: can duplicated genes diverge fast enough to escape conversion?Genetics 117: 543–557, 1987

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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The nucleotide sequence data reported in this paper have been submitted to the EMBL/GenBank nucleotide sequence databases and have been assigned the accession numbers L36567 (DRB1 * 1) L36568 (DRB1 * 2), L36569 (DRB1 * 3), L36570 (DRB1 * 4), L36571 (DRB1 * 5), L36572 (DRB1 * 6), L36573 (DRB1 * 7), L36574 (DRB1 * 8), L36575 (DRB2 * 1), L36576 (DRB2 * 2A), L36577 (DRB2 * 2B), L36578 (DRB2 * 2C), L36579 (DRB1 * 2D), L36580 (DRB2 * 3), L36581 (DRB2 * 4), L36582 (DRB3 * 1A), L36583 (DRB3 * 1B), L36584 (DRB3 * 1C), L36585 (DRB3 * 1D)

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Brunsberg, U., Edfors-Lilja, I., Andersson, L. et al. Structure and organization of pigMHC class IIDRB genes: evidence for genetic exchange between loci. Immunogenetics 44, 1–8 (1996). https://doi.org/10.1007/BF02602651

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  • DOI: https://doi.org/10.1007/BF02602651

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