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.
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
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
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
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
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
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
Barran, P. A. and McMaster, W. R.: DNA sequence analysis of the rat RTI. Bα gene. Immunogenetics 26: 56–62, 1987
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
Berget, S. M.: Are U4 small nuclear ribonucleoproteins involved in polyadenylation? Nature 309: 179–182, 1984
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
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
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
Breathnach, R. and Chambon, P.: Organisation and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem 50: 349–383, 1981
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
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
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
Chomczynski, P. and Sacchi, N.: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Bioch 162: 156–159, 1987
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
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
Figueroa, F., Gutknecht, J., Tichy, H., and Klein, J.: Class II Mhc genes in rodent evolution. Immunol Rev 113: 27–46, 1990
Figueroa, F. and Klein, J.: The evolution of MHC class II genes. Immunol Today 7: 78–81, 1986
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
George, D. G., Barker, W. C., and Hunt, L. T.: The protein identification resource (PIR). Nucleic Acids Res 14: 11–15, 1986
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
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
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
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
Kappes, D. J. and Strominger, J. L.: Human class II major histocompatibility complex genes and proteins. Annu Rev Biochem 57: 991–1028, 1988
Klein, J. and Figueroa, F.: Evolution of the major histocompatibility complex. Crit Rev Immunol 6: 295–386, 1986
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
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
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
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
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
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
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
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
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
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
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
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
Rask, L., Andersson, L., Gustafsson, K., and Jonsson, A.-K.: Parsimony analysis of mammalian class II histocompatibility genes. Immunol Rev 113: 187–206, 1990
Sambrook, J., Fritsch, E. F., and Maniatis, T.: Molecular cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 1989
Sanger, F., Nicklen, S., and Coulson, A. R.: DNA sequencing with chain terminating inhibitors. Proc Natl Acad Sci USA 74: 5463–5467, 1977
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
Scott, P. C., Choi, C.-L., and Brandon, M. R.: Genetic organisation of the ovine MHC class II region. Immunogenetics 25: 116–122, 1987
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
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
Steinmetz, M. and Hood, L.: Genes of the major histocompatibility complex in mouse and man. Science 222: 727–733, 1983
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
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
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
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
Author information
Authors and Affiliations
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
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
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00211419