Abstract
The expressed major histocompatibility complex (Mhc) class II DRB genes of 50 unrelated deer were examined by reverse transcription polymerase chain reaction, cloning, and sequencing of DRB exon 2. Deer, like other mammals, have at least one highly polymorphic Mhc class II DRB gene. Thirty-four different sequences were identified. Most of the variation in amino acid composition occurred at positions that have been shown to form the peptide binding site (PBS). Eighteen deer-specific substitutions were found, 11 of these occurred in the PBS. Significantly higher rates of replacement substitutions than silent substitutions were found in the deer sequences, indicating strong positive selection pressure for diversity in DRB sequences. Between one and four DRB sequences were found per deer. Inheritance of these sequences in pedigrees showed Mendelian segregation with up to two expressed DRB genes per haplotype. Sheep are the only other ruminant in which the presence of more than one expressed DRB gene has been demonstrated. Phylogenetic trees were constructed in an attempt to assign the deer DRB sequences to specific loci, but no clear segregation of the DRB sequences for different loci was found. It would seem likely that sequence exchange between the loci has occurred. As has been shown in other species, the α-helix and β-sheet regions of exon 2 appeared to have different evolutionary histories.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ammer, H., Schwaiger, F.-W., Kammerbauer, C., Gomolka, M., Arriens, A., Lazary, S., and Epplen, J. T. Exonic polymorphism versus intronic simple repeat hypervariability in Mhc DRB genes. Immunogenetics 32: 330–337, 1992
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
Ballingall, K. T., Wright, H., Redmond, J., Dutia, B. M., Hopkins, J., Lang, J., Deverson, E. V., Howard, J. C., Puri, N., and Haig, D. Expression and characterization of ovine major histocompatibility complex class II (OLA-DR) genes. Anim Genet 23: 347–359, 1992
Bodmer, J. G., Marsh, S. G. E., Albert, E. D., Bodmer, W. F., Dupont, B., Erlich, G. M., Mach, B., Mayr, W. R., Parham, P., Sasazuki, T., Schreuder, G. M., Strominger, J. L., Svejgaard, A., and Terasaki, P. I. Nomenclature for Factors of the HLA System, 1994. Tissue Antigens 44: 1–18, 1994
Brandle, U., Ono, H., Vincek, V., Klein, D., Golubic, M., Grahovac, B., and Klein, J. Trans-species evolution of Mhc-DRB haplotype polymorphism in primates: organization of DRB genes in the chimpanzee. Immunogenetics 36: 39–48, 1992
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 antigen HLA-DR1. Nature 364: 33–39, 1993
Burke, M. G., Stone, R. T., and Muggli-Cockett, N. E. Nucleotide sequence and northern analysis of a bovine major histocompatibility class II DRB like cDNA. Anim Genet 22: 343–349, 1991
Chirgwin, J. M., Przybyla, A. E., McDonald, R. R., and Rutter, W. J. Isolation of biologically active RNA from sources enriched in ribonuclease. Biochemistry 18: 5267–5530, 1979
Dutia, B. M., McConnell, I., Ballingall, K. T., Keating, P., and Hopkins, J. Evidence for the expression of two distinct MHC class II DRB like molecules in the sheep. Anim Genet 25: 235–241, 1994
Erlich, H. A. and Gyllensten, U. B. Shared epitopes among HLA class II alleles: gene conversion, common ancestry and balancing selection. Immunol Today 12: 411–414, 1991
Griffin, J. F. T., Cross, J. P., and Bucham, G. S. Tubercolosis in domesticated red deer: comparison of purified protein derivative and the specific protein MPB70 for in vitro diagnosis. Res Vet Sci 50: 279–285, 1991
Groenen, M. A. M., van der Poel, J. J., Dijkhof, R. J. M., and Giphant, M. J. The nucleotide sequence of bovine Mhc class II DQB and DRB genes. Immunogenetics 31: 37–44, 1990
Gustafsson, K., Germana, S., Hirsch, F., Pratt, K., LeGuern, C., and Sach, D. H. Structure of miniature swine class II DRB genes: conservation of hypervariable amino acid residues between distantly related mammalian species. Proc Natl Acad Sci USA 87: 9798–9802, 1990
Gyllensten, U. B., Sundvall, M., and Erlich, H. A. Allelic diversity is generated by intraexon sequence exchange at the DRB1 locus of primates. Proc Natl Acad Sci 88: 3686–3690, 1991
Hordvik, I., Grimbolt, U., Fosse, V. M., Lie, O., and Endressen, C. Cloning and sequence analysis of cDNAs encoding the MHC class II b chain in Atlantic salmon (Salmo salar). Immunogenetic 37: 437–441, 1993
Hughes, A. L. and Nei, M. Nucleotide substitution at major histocompatibility complex class II loci: evidence for over-dominant selection. Proc Natl Acad Sci USA 86: 958–962, 1989
Jeffreys, A. J., Neumann, R., and Wilson, V. Repeat unit sequence variation in minisatellites: a novel source of DNA polymorphism for studying variation and mutation by single molecule analysis. Cell 60: 473–485, 1990
Klein, J. Natural History of the Major Histocompatibility Complex, John Wiley and Sons, New York, 1986
Klein, J. Origin of major histocompatibility complex polymorphism: the trans-species hypothesis. Hum Immunol 19: 155–162, 1987
Kovalic, D., Kwak, J., and Weisblum, B. General method for the direct cloning of DNA fragments generated by the polymerase chain reaction. NAR 19: 4560–4566, 1991
Kenter, M., Otting, N., Anholts, J., Jonker, M., Schipper, R., and Bontrop, R. E. Mhc-DRB diversity of the chimpanzee (Pan troglodytes). Immunogenetics 37: 1–11, 1992
Marsh, S. G. E. and Bodmer, J. G. HLA class II nucleotide sequences, 1992. Immunogenetics 37: 79–94, 1992
Muggli-Cockett, N. E. and Stone, R. T. Identification of genetic variation in the bovine Mhc DRB-like genes using sequenced bovine genomic probes. Anim Genet 19: 213–225, 1988
Nei, M. and Gojobori, T. Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 3: 418–426, 1986
O'hUigin, C., Bontrop, R., and Klein, J. Nonhuman primate Mhc-DRB sequences: a compilation. Immunogenetics 38: 165–183, 1993
Potts, W. K. and Wakeland, E. K. Evolution of diversity at the major histocompatibility complex. TREE 5, No 6: 181–187, 1990
Rask, I., Gustafsson, K., Larhammer, D., Ronne, H., and Peterson, P. A. Generation of class II antigen polymorphism. Immunol Rev 84: 123–143, 1985
Rollini, P., Mach, G., and Gorski, J. Linkage map of 3 HLA-DR B-chain genes: Evidence for a recent duplication event. Proc Natl Acad Sci USA 82: 7197–7201, 1985
Sarmiento, U. M., Sarmiento, J. I., and Storb, R. Allelic variation in the DR subregion of the canine major histocompatibility complex. Immunogenetics 32: 13–19, 1993
Schwaiger, F., Weyers, E., Epplen, C., Ruff, G., Crawford, A. M., and Epplen, J. T. The paradox of MHC-DRB exon/intron evolution: α-helix and β-sheet encoding regions diverge while hypervariable intronic simple repeats co-evolve with b-sheet codons. J Mol Evol 37: 260–272, 1993
Schwaiger, F., Weyers, E., Buitkamp, J., Ede, A. J., Crawford, A. M., and Epplen, J. T. Interdependent MHC-DRB exon plus intron evolution in artiodactyls. Mol Biol Evol 11: 239–244, 1994
She, J. X., Boehme, S. A., Wang, T. W., Bonhomme, F., and Wakeland, E. K. Amplification of major histocompatibility complex class II gene diversity by intraexonic recombination. Proc Natl Acad Sci USA 88: 453–457, 1991
Sigurdardottir, S., Borsch, C., Gustafsson, K., and Andersson, L. Cloning and sequence analysis of 14 DRB alleles of the bovine major histocompatibility complex by using the polymerase chain reaction. Anim Genet 22: 199–209, 1991
Sorrentino, R., Lillie, J., and Strominger, J. L. Molecular characterization of MT3 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
Stone, R. T. and Muggli-Cockett, N. E. Partial nucleotide sequence of a novel bovine Mhc class II B-chain, CoLA-DIB. Anim Genet 21: 353–360, 1990
Stunz, L. L., Karr, R. W., and Anderson, R. A. HLA-DRB1 and DRB4 genes are differentially regulated at the transcriptional of level. J Immunol 143: 3081–3086, 1989
The WHO Nomenclature Committee. Nomenclature for factors of the HLA system. Immunogenetics 36: 135–148, 1991
Xu, A., Park, C., and Lewin, H. A. Both DQB genes are expressed in BoLA haplotypes carrying a duplicated DQ region. Immunogenetics 39: 316–321, 1994
Author information
Authors and Affiliations
Additional information
The nucleotide sequence data reported in this paper have been submitted to the EMBL/Genbank nucleotide sequence database and have been assigned the accession numbers of U11101 (Ceel-DRB1), U11102 (Ceel-DRB2), U11103 (Ceel-DRB3), U11104 (Ceel-DRB4), U11105 (Ceel-DRB5), U11106 (Ceel-DRB6), U11107 (Ceel-DRB7), U11108 (Ceel-DRB8), U11110 (Ceel-DRB10), U11111 (Ceel-DRB11), U11112 (Ceel-DRB12), U11113 (Ceel-DRB13), U11114 (Ceel-DRB14), U11115 (Ceel-DRB15), U11116 (Ceel-DRB16), U11118 (Ceel-DRB18), U11119 (Ceel-DRB19), U11121 (Ceel-DRB21), U11123 (Ceel-DRB24), U11212 (Ceel-DRB27), U11213 (Ceel-DRB28),U11215 (Ceel-DRB30), U11216 (Ceel-DRB31), U11217 (Ceel-DRB32), U11218 (Ceel-DRB33), U11225 (Ceel-DRB40). U11226 (Ceel-DRB41), U11227 (Ceel-DRB42), U11228 (Ceel-DRB43), U11229 (Ceel-DRB44), U11230 (Ceel-DRB45), U11231 (Ceel-DRB46), U11233 (Ceel-DRB48), U11234 (Ceel-DRB49)
Rights and permissions
About this article
Cite this article
Swarbrick, P.A., Schwaiger, FW., Epplen, J.T. et al. Cloning and sequencing of expressed DRB genes of the red deer (Cervus elaphus) Mhc . Immunogenetics 42, 1–9 (1995). https://doi.org/10.1007/BF00164981
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00164981