Abstract
Fifty-four chimpanzee Patr-DRB and five human HLA-DRB second exons were cloned and sequenced from thirty-five chimpanzees and four B-cell lines and compared with known Mhc-DRB sequences of these two species. Equivalents of the HLA-DRB1 *02,-DRB1 * 03, -DRB1 * 07 allelic lineages and the HLA-DRB3,-DRB4, -DRB5, -DRB6, and -DRB7 loci were all found in the chimpanzee. In addition, two chimpanzee Patr-DRB lineages (Patr-DRBX and -DRBY) were found for which no human counterparts have been described. None of the Patr-DRB sequences is identical to known HLA-DRB sequences. The Patr-DRB1 * 0702 and HLA-DRB1 * 0701 alleles are the most similar sequences in a comparison between the two species and differ by only two nucleotides out of 246 sequences. Equivalents of the HLA-DRB1 * 01,-DRB1 * 04, and -DRB1 * 09 alleles were not found in our sample of chimpanzees. A per locus comparison of the number of Patr-DRB alleles with the HLA-DRB alleles shows that the Patr-DRB3, -DRB4, -DRB5, and -DRB6 locus are, thus far, more polymorphic than ther human homologs. The polymorphism of the Patr-DRB1 locus seems to be less extensive than that reported for the HLA-DRB1 locus. Nevertheless, the Patr-DRB1 locus seems to be the most polymorphic of the Patr-DRB loci. Phylogenetic analyses indicate that the HLA-DRB1 * 09 allele may have originated from a recombination between a Mhc-DRB5 allele and the DRB1 allele of a Mhc-DR7 haplotype. Although recombination seems to increase the diversity of the Patr-DRB alleles, its contribution to the generation of Patr-DRB variation is probably low. Hence, most Patr-DRB diversity presumably accumulated via recurrent point mutations. Finally, two distinct PAtr-DRB haplotypes are deduced, one of which (the chimpanzee equivalent of the HLA-Dr7 haplotype) is probably older than 6–8 million years.
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References
Andersson, G., Larhammer, 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
Andrews, P.: Fossil evidence on human origins and dispersal. Cold spring Harb Symp Biol: 419–428, 1986
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 in constant. J Immunol 135: 2149–2155, 1985
Bontrop, R. E., Otting, N., Broos, L. A. M., Noort, M. C., Kenter, M., and Jonker, M.: RFLP analysis of the HLA-, ChLA-, and RhLA-DQ alpha chain gene regions: conservation of restriction sites during evolution. Immunogenetics 30: 432–439, 1989
Bontrop, R. E., Broos, L. A. M., Pham, K., Bakas, R., 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: 272–290, 1990
Brown, J. H., Jerdetzky, T., Saper, M. A., Samraoui, B., Bjorkman, P. J., and Wiley, D. C.: A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature 332: 845–850, 1988
Bullock, W. O., Fernandez, J. M., and Short, J. M.: XL1-Blue: a high efficiency plasmid transformation rec A Escherichia coli strain with beta-galactosidase selection. Biotechniques 5: 376–378, 1987
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 haplotypes distribution of a new HLA-DRB gene: HLA-DRBδ. Mol Immunol 28: 533–543, 1991
Deverex, J., Haeberli, P., and Smithies, O.: A comprehensive set of sequence analysis programs for the VAX. Nucleic Acid Res 12: 387–395, 1984
Fan, W., Kasahara, M., Gutknecht, J., Klein, D., Mayer, W. E., Jonker, M., and Klein, J.: Shared class II MHC polymorphism between humans and chimpanzees. Hum Immunol 26: 107–121, 1989
Felsenstein, J.: Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39: 783–791, 1985
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
Gorski, J. and Mach, B.: Polymorphism of human Ia antigens: gene conversion between two DRβ loci results in a new HLA-D/DR specificity. Nature 322: 67–70, 1986
Gyllensten, U. B., Sundvall, M., and Erlich, H.: Allelic diversity is generated by intraexon sequence exchange at the DRB1 locus of primates. Proc Natl Acad Sci USA 88: 3686–3690, 1991a
Gyllensten, U., Sundvall, M., Ezcurra, I., and Erlich, H.: Genetic diversity at class II DRB loci of the primate MHC. J Immunol 146: 4368–4376, 1991b
Haas, D. A., Boss, J. M., Strominger, J. L., and Spies, T.: A highly deverged β1 exon in the DR region of the human MHC: sequence and evolutionary implications. Immunogenetics 25: 15–20, 1987
Higgins, D. G., Bleasy, A. J., and Fuchs, R.: CLUSTAL V: improved software for multiple sequence alignments. CABIOS 8: 189–191, 1992
Hughes, A. L. and Nei, M.: Nucleotide substitutions at major histocompatibility complex class II loci: evidence for overdominant selection. Proc Natl Acad Sci USA 86: 958–962, 1989
Hughes, A. L.: Testing for interlocus genetic exchange in the MHC a reply to Andersson and co-workers. Immunogenetics 33: 243–246, 1991
Kapper, D. and Strominger, J. L.: Human class II major histocompatibility complex genes and proteins. Annu Rev Biochem 57: 991–1028, 1988
Kasahara, M., Klein, D., Fan, W., and Gutknecht, J.: Evolution of the class II major histocompatibility complex alleles in higher primates. Immunol Rev 113: 65–82, 1990
Kelly, A. P., Monaca, J. J., Cho, S., and Trowsdale, J.: A new human HLA class II locus, DM. Nature 353: 571–573, 1991
Kenter, M., Anholts, J., Ruff, G., Otting, N., and Bontrop, R. E. Selective inactivation of the primate Mhc-DQA2 locus. In J. Klein and D. Klein (eds.): Molecular Evolution of the Major Histocompatibility Complex, pp. 213–220, Springer Verlag, Heidelberg, 1991
Kenter, M., Otting, N., Anholts, J., Leunissen, J., Jonker, M., and Bontrop, R. E.: Evolutionary relationships among the primate Mhc-DQA1 and DQA2 alleles. Immunogenetics 36: 71–78, 1992
Kieny, M. P., Lathe, R., and Lecocq, J. P.: New versatile cloning and sequencing vectors based on bacteriophage M13. Gene 26: 91–99, 1983
Kimura, M.: Estimation of evolutionary distances between nucleotide sequences. Proc Natl Acad Sci USA 78: 454–458, 1981
King, L. B., Sharma, S., and Corley, R. B.: Complete coding region sequence of Eβk cDNA clones: Lack of polymorphism in the NH2-terminus between Eβk and Eβb molecules. J of Immunogenetics 15: 209–214, 1988
Klein, J.: Origin of major histocompatibility complex polymorphism: the trans species hypothesis. Hum Immunol 19: 155–162, 1987
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
Klein, D., Vincek, V., Kasahara, M., Schönbach, C., O'hUigin, C., Klein, J.: Gorilla major histocompatibility complex-DRB pseudogene orthologous to HLA-DRBVIII. Hum Immunol 32: 211–220, 1991a
Klein, J., O'hUigin, C., Kasahara, M., Vincek, V., Klein, D., and Figueroa, F.: Frozen haplotypes in Mhc evolution. In J. Klein and D. Klein (eds.): Molecular Evolution of the Major Histocompatibility Complex, pp. 261–286, Springer-Verlag, Heidelberg, 1991b
Klein, J., Satta, Y., O'hUigin, C., Mayer, W. E., and Takahata, N.: Evolution of the primate DRB region. In T. Sasazuki (ed.): HLA 1991, Vol 2, Proceedings of the 11th International Histocompatibility Workshop, Yokohama, Japan. Oxford University Press, Oxford, 1992
Larhammer, D., Servenius, B., Rask, L., and Peterson, P. A.: Characterization of an HLA-DRβ pseudogene. Proc Natl Acad Sci USA 82: 1475–1479, 1985
Maniatis, T., Fritsch, E. F., and Sambrook, J.: Molecular cloning: A laboratory manual. Cold Spring Harbor Laboratory, New York, 1982
Marsh, S. G. E. and Bodmer, J. G.: HLA Class II Nucleotide Sequences 1991. Hum Immunol 31: 207–227, 1991
Meunier, H. F., Carson, S., Bodmer, W. F., and Trowsdale, J.: An isolated β1 exon next to the DRα gene in the HLA-D region. Immunogenetics 23: 172–180, 1986
Nei, M. and Gojobori, T.: Simple methods for estimating the number of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 3: 418–426, 986
Nei, M. and Rzhetsky, A.: Reconstruction of phylogenetic trees and evolution of major histocompatibility complex genes. In J. Klein and D. Klein (eds.): Molecular Evolution of the Major Histocompatibility Complex, pp. 13–27, Springer Verlag, Heiderlberg, 1991
Olerup, O., Troye-Blomberg, M., Schreuder, G. M. T., and Riley, E. M.: HLA-DR and -DQ gene polymorphism in West Africans is twice extensive as in North European Caucasians: Evolutionary implication. Proc Natl Acad Sci USA 88: 8480–8484, 1991
Otting, N., Kenter, M., van Weeren, P., Jonker, M., and Bontrop, R. E.: Mhc-DQB repertoire variation in hominoid and Old World primate species. J Immunol, in press, 1992
Rollini, P., Mach, B., and Gorski, J.: Linkage map of three HLA-DRβ chain genes: Evidence for a recent duplication event. Proc Natl Acad Sci USA 82: 7197–7201, 1985
Rollini, P., Gorski, J., and Mach, B.: Characterization of an HLA-DRβ pseudogene in the DRw52 supertypic group. Immunogenetics 25: 336–342, 1987
Ruvolo, M., Disorell, T., Allard, M. W., Brown, W. M., and Honeycutt, R. L.: Resolution of the African hominoid trichotomy by use of a mitochondrial gene sequence. Proc Natl Acad Sci USA 88: 1570–1574, 1991
Saiki, R. K., Scharf, S., Faloona, F., Mullis, K. B., Horn, G. T., Erlich, H. A., and Arnheim, N.: Enzymatic amplification of β-globin genomic sequences and restriction site analysis of sickle cell anaemia. Science 230: 1350–1354, 1985
Saiki, R. K., Gelfand, D. H., Stoffel, S., Scharf, S. J., Higuchi, R., Horn, G. T., Mullis, K. B., and Erlich, H. A.: Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239: 487–491, 1988
Saitou, N. and Nei, M.: The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4: 406–425, 1987
Sanger, F., Nicklen, S., and Carlson, R.: DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 77: 5463–5467, 1977
Trowsdale, J., Ragoussis, J., and Campbell, R. D.: Map of the human MHC. Immunol Today 12: 443–446, 1991
Vincek, V., Klein, D., Figueroa, F., Hauptvield, V., Kasahara, M., O'hUigin, C., Mach, B., and Klein, J.: The evolutionary origin of the HLA-DR3 haplotype. Immunogenetics 35: 263–271, 1992
WHO Nomenclature Committee: Nomenclature for factors of the HLA system, 1991. Tissue Antigens 39: 1–13, 1992
Wu, S., Sauders, T. L., and Bach, F.: Polymorphism of human Ia antigens generated by reciprocal intergenic exchange between two DRβ loci. Nature 324: 676–679, 1986
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The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide database and have been assigned the accession numbers Mg6074-Mg6132.
Correspondence to: M. Kenter.
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Kenter, M., Otting, N., Anholts, J. et al. Mhc-DRB diversity of the chimpanzee (Pan troglodytes). Immunogenetics 37, 1–11 (1992). https://doi.org/10.1007/BF00223539
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DOI: https://doi.org/10.1007/BF00223539