Skip to main content
Log in

Nucleotide sequence, polymorphism, and evolution of ovine MHC class II DQA genes

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

Abstract

The nucleotide sequence of all exons and introns, excluding exon 1, of the ovine major histocompatibility complex (MhcOvar) genes analogous to the HLA-DQA1 and -DQA2 genes has been determined and the gene structure found to be similar to that reported for other species. The predicted amino acid sequences of the Ovar-DQA genes have been compared with the equivalent DQA genes in man, mouse, rat, rabbit, and cattle and used to determine the evolutionary relationships of the sheep class II genes to these other species. Northern blot analysis of sheep mRNA using exon specific probes for each of the two Ovar-DQA genes show that both genes are transcribed, whereas in humans there is no evidence that HLA-DQA2 is transcriptionally active. Restriction fragment length polymorphisms (RFLPs) have been used to define a polymorphic series of alleles in both Ovar-DQA genes and have indicated that the number of DQA genes is not constant in sheep as it is in humans, but varies with the haplotype.

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

  • Andersson, L. and Rask, L.: Characterization of the MHC class II region in cattle. The number of DQ genes varies between haplotypes. Immunogenetics 27: 110–120, 1988

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

    Google Scholar 

  • Andersson, L., Lunden, A., Sigurdarottir, S., Davies, C. J., and Rask, L.: Linkage relationships in the bovine MHC region. High recombination frequency between class II subregions. Immunogenetics 27: 273–280, 1988

    Google Scholar 

  • Auffray, C., Lillie, J. W., Arnot, D., Grossberger, D., Kappes, D., and Strominger, J. L.: Isotypic and allotypic variation of human class II histocompatibility antigen α-chain genes. Nature 308: 327–333, 1984

    Google Scholar 

  • Auffray, C., Lillie, J. W., Korman, A. J., Boss, J. M., Frechin, 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: 63–73, 1987

    Google Scholar 

  • Aviv, H. and Leder, P.: Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci USA 69: 1408–1412, 1972

    Google Scholar 

  • Barran, P. A. and McMaster, W. R.: DNA sequence analysis of the rat RTI. Bα gene. Immunogenetics 26: 56–62, 1987

    Google Scholar 

  • Beller, D. I. and Unanue, E. R.: Regulation of macrophage populations. II. Synthesis and expression of Ia antigens by peritoneal exudate macrophages is a transient event. J Immunol 126: 263–269, 1981

    Google Scholar 

  • Berget, S. M.: Are U4 small nuclear ribonucleoproteins involved in polyadenylation? Nature 309: 179–182, 1984

    Google Scholar 

  • Bidwell, J. L., Bidwell, E. A., Savage, D. A., Middleton, D., Klouda, P. T., and Bradley, B. A.: A DNA-RFLP typing system that positively identifies serologically well-defined and ill-defined HLA-DR and DQ alleles, including DRw10. Transplantation 45: 640–646, 1988

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • Breathnach, R. and Chambon, P.: Organisation and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem 50: 349–383, 1981

    Article  CAS  PubMed  Google Scholar 

  • Carlsson, B., Wallin, J., Böhme, J., and Möller, E.: HLA-DR-DQ haplotypes defined by restriction fragment analysis, correlation to serology. Hum Immunol 20: 95–113, 1987

    Google Scholar 

  • Chang, H.-C., Moriuchi, T., and Silver, J.: The heavy chain of human B-cell alloantigens HLA-DS has a variable N-terminal region and a constant immunoglobulin like region. Nature 305: 813–815, 1983

    Google Scholar 

  • Chardon, P., Kirszenbaum, M., Cullen, P. R., Geffrotin, C., Auffray, C., Strominger, J. L., Cohen, D., and Vaiman, M.: Analysis of the sheep MHC using HLA class I, II, and C4 cDNA probes. Immunogenetics 22: 349–358, 1985

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Cox, N. J., Mela, A. P., Zmijewski, C. M., and Spielman, R. S.: HLA-DR typing “at the DNA level”: RFLPs and subtypes detected with a DRβ cDNA probe. Am J Hum Genet 43: 954–963, 1988

    Google Scholar 

  • Dunham, I., Sargent, C. A., Dawkins, R. L., and Campbell, R. D.: An analysis of variation in the long-range genomic organization of the human major histocompatibility complex class II region by pulsed-field gel electrophoresis. Genomics 5: 787–796, 1989

    Google Scholar 

  • Figueroa, F., Gutknecht, J., Tichy, H., and Klein, J.: Class II Mhc genes in rodent evolution. Immunol Rev 113: 27–46, 1990

    Google Scholar 

  • Figueroa, F. and Klein, J.: The evolution of MHC class II genes. Immunol Today 7: 78–81, 1986

    Google Scholar 

  • Flavell, R. A., Allen, H., Huber, B., Wake, C., and Widera, G.: Organisation and expression of the MHC of the C57 Black/10 mouse. Immunol Rev 84: 29–50, 1985

    Google Scholar 

  • George, D. G., Barker, W. C., and Hunt, L. T.: The protein identification resource (PIR). Nucleic Acids Res 14: 11–15, 1986

    Google Scholar 

  • Gogolin, K. J., Kolaga, V. J., Baker, L., Lisak, R. P., Zmijewski, C. M., and Spielman, R. S.: Subtypes of HLA-DQ and-DR defined by DQB1 and DRB1 RFLPs: allele frequencies in the general population and in insulin-dependent diabetes (IDDM) and multiple sclerosis patients. Ann Hum Genet 53: 327–338, 1989

    Google Scholar 

  • Gogolin-Ewens, K. J., Meeusen, E. N. T., Scott, P. C., Adams, T. E., and Brandon, M. R.: Genetic selection for disease resistance and traits of economic importance in animal production. OIE Scientific Technical Rev 9 : 865–896, 1990

    Google Scholar 

  • Grossberger, D., Hein, H., and Marcuz, A.: Class I major histocompatibility complex cDNA clones from sheep thymus: alternative splicing could make a long cytoplasmic tail. Immunogenetics 32: 77–87, 1990

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    CAS  PubMed  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, 1990a

    CAS  PubMed  Google Scholar 

  • Klein, J., Benoist, C., Davis, C. S., Demant, P., Fischer Lindahl, K., Flaherty, L., Flavell, R. A., Hämmerling, U., Hood, L. E., Hunt, S. W., III, Jones, P. P., Kourilsky, P., McDevitt, H. O., Meruelo, D., Murphy, D. B., Nathenson, S. G., Sachs, D. H., Steinmetz, M., Tonegawa, S., Wakeland, E. K., and Weiss, E. H.: Revised nomenclature for mouse H-2 genes. Immunogenetics 32: 147–149, 1990b

    Google Scholar 

  • Kohonen-Corish, M. R. J. and Serjeantson, S. W.: HLA-DRβ gene DNA polymorphisms revealed by Taq I correlate with HLA-DR specificities. Hum Immunol 15: 263–271, 1986

    Google Scholar 

  • Korman, A. J., Frantz, J. D., Strominger, J. L., and Mulligan, R. C.: Expression of human class II major histocompatibility complex antigens using retrovirus vectors. Proc Natl Acad Sci USA 84: 2150–2154, 1987

    Google Scholar 

  • Landais, D., Matthes, H., Benoist, C., and Mathis, D.: A molecular basis for the Ia.2 and Ia.19 antigenic determinants. Proc Natl Acad Sci USA 82: 2930–2934, 1985

    Google Scholar 

  • Larhammar, D., Schenning, L., Gustafsson, K., Wiman, K., Claesson, L., Rask, L., and Peterson, P. A.: Complete amino acid sequence of an HLA-DR antigen-like β chain as predicted from the nucleotide sequence: Similarities with immunoglobulins and HLA-A,-B,-C antigens. Proc Natl Acad Sci USA 79: 3687–3691, 1982

    Google Scholar 

  • Le Guern, C., Weissman, J. D., Marche, P. N., Jouvin-Marche, E., Laverriere, A., Bagnato, M. R., and Kindt, T. J.: Sequence determination of a transcribed rabbit class II gene with homology to HLA-DQα. Immunogenetics 25: 104–109, 1987

    Google Scholar 

  • Millot, P., Chatelain, J., and Cathala, F.: Sheep major histocompatibility complex OLA: Gene frequencies in two French breeds with scrapie. Immunogenetics 21: 117–123, 1985

    Google Scholar 

  • Needleman, S. B. and Wunsch, C. D.: A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol 48: 443–453, 1970

    CAS  PubMed  Google Scholar 

  • Ostergard, H., Kristensen, B., and Andersen, S.: Investigations in farm animals of associations between the MHC system and disease resistance and fertility. Livestock Prod Sci 22: 49–67, 1989

    Google Scholar 

  • Puri, N. K., Gogolin-Ewens, K. J., and Brandon, M. R.: Monoclonal antibodies to sheep MHC class I and class II molecules: Biochemical characteristation of three class I gene products and four distinct sub-populations of class II molecules. Vet Immunol Immunopathol 15: 59–86, 1987a

    Google Scholar 

  • Puri, N. K., Walker, I. D., and Brandon, M. R.: N-terminal amino acid sequence analyses of the α and β polypeptides from four distinct subsets of sheep major histocompatibility complex class II molecules. J Immunol 139: 2996–3002, 1987b

    Google Scholar 

  • Rask, L., Andersson, L., Gustafsson, K., and Jonsson, A.-K.: Parsimony analysis of mammalian class II histocompatibility genes. Immunol Rev 113: 187–206, 1990

    Google Scholar 

  • Sambrook, J., Fritsch, E. F., and Maniatis, T.: Molecular cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 1989

    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 

  • Schiffenbauer, J., Didier, D. K., Klearman, M., Rice, K., Shuman, S., Tieber, V. L., Kittlesen, D. J., and Schwartz, B. D.: Complete sequence of the HLA DQα and DQβ cDNA from a DR5/DQw3 cell line. J Immunol 139: 228–233, 1987

    Google Scholar 

  • Scott, P. C., Choi, C.-L., and Brandon, M. R.: Genetic organisation of the ovine MHC class II region. Immunogenetics 25: 116–122, 1987

    Google Scholar 

  • Scott, P. C., Maddox, J. F., Gogolin-Ewens, K. J., and Brandon, M. R.: The nucleotide sequence of ovine MHC class II B genes: DQB and DRB. Immunogenetics 34: this issue

  • Shoshani, J.: Mammalian phylogeny: Comparison of morphological and molecular results. Mol Biol Evol 3: 222–242, 1986

    Google Scholar 

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

    Google Scholar 

  • Steinmetz, M. and Hood, L.: Genes of the major histocompatibility complex in mouse and man. Science 222: 727–733, 1983

    Google Scholar 

  • Swofford, D. L. and Olsen, G. J.: Phylogeny reconstruction. In D. M. Hillis and C. Moritz (eds.): Molecular Systematics, pp. 411–501, Sinauer Associates Inc., sunderland, Massachusetts, 1990

    Google Scholar 

  • Travers, P. and McDevitt, H. O.: Molecular genetics of class II (Ia) antigens. In M. Sela (ed.): The Antigens, Vol. 7, pp. 147–211, Academic Press, Orlando, Florida, 1987

    Google Scholar 

  • Trowsdale, J., Young, J. A. T., Kelly, A. P., Austin, P. J., Carson, S., Meunier, H., So, A., Erlich, H. A., Spielman, R. S., Bodmer, J., and Bodmer, W. F.: Structure, sequence and polymorphism in the

  • Van der Poel, J. J., Groenen, M. A. M., Djkhof, R. J. M., Ruyter, D., and Giphart, M. J.: The nucleotide sequence of the bovine MHC class II alpha genes: DRA, DQA, and DYA. Immunogenetics 31: 29–36, 1990

    Google Scholar 

  • Watters, J. W. F., Locker, J. D., Kunz, H. W., and Gill, T. J.: Polymorphism and mapping of the class II genes in the rat: RT1.B, RT1.D, and RT1.H, a new DP-like region. Immunogenetics 26: 220–229, 1987

    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 M33304 and M33305.

Address correspondence and offprint requests to: M. R. Brandon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Scott, P.C., Gogolin-Ewens, K.J., Adams, T.E. et al. Nucleotide sequence, polymorphism, and evolution of ovine MHC class II DQA genes. Immunogenetics 34, 69–79 (1991). https://doi.org/10.1007/BF00211419

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00211419

Keywords

Navigation