Abstract
Recent data suggest that HLA-B locus alleles can evolve quickly in native South American populations. To investigate further this phenomenon of new HLA-B variants among Amerindians, we studied samples from another South American tribe, the Cayapa from Ecuador. We selected individuals for HLA-B molecular typing based upon their HLA class II typing results. Three new variants of HLA-B39 and one new variant of HLA-B15 were found in the Cayapa: HLA-B *3905, HLA-B*3906, HLA-B*3907, and HLA-B *1522. A total of thirteen new HLA-B alleles have now been found in the four South American tribes studied. Each of these four tribes studied, including the Cayapa, had novel alleles that were not found in any of the other tribes, suggesting that many of these new HLA-B alleles may have evolved since the Paleo-Indians originally populated South America. Each of these 13 new alleles contained predicted amino acid replacements that were located in the peptide binding site. These amino acid replacements may affect the sequence motif of the bound peptides, suggesting that these new alleles have been maintained by selection. New allelic variants have been found for all common HLA-B locus antigenic groups present in South American tribes with the exception of B48. In spite of its high frequency in South American tribes, no evidence for variants of B48 has been found in all the Amerindians studied, suggesting that B48 may have unique characteristics among the B locus alleles.
The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession numbers U14756 (HLA-B *1522), U15683 (HLA-B *3905), U15639 (HLA-B *3906), and U15640 (HLA-B *3907)
Similar content being viewed by others
References
Allsopp, C. E. M., Hill, A. V. S., Kwiatkowski, D., Hughes, A., Bunce, M., taylor, C. J., Pazmany, L., Brewster, D., McMichael, A. J., and Greenwood, B. M. Sequence analysis of HLA-Bw53, a common West African allele, suggests an origin by gene conversion of HLA-B35. Hum Immunol 30: 104–109, 1991
Barriga López, F. Etnologia ecuatoriana, v. 4, Cayapas o Chachis. Instituto Ecuatoriano de Crédito Educativo y Becas, Gráficas Duque, Quito, Ecuador, 1987
Belich, M. P., Madrigal, J. A., Hildebrand, W. H., Zemmour, J., Williams, R. C., Luz, R., Petzl-Erler, M. L., and Parham, P. Unusual HLA-B alleles in two tribes of Brazilian Indians. Nature 357: 326–329, 1992
Bjorkman P. J., Saper, M. A., Samraoui, B., Bennet, W. S., Strominger, J. L., and Wiley, D. C. Structure of human class I histocompatibility antigen HLA-A2. Nature 329: 506–512, 1987a
Bjorkman, P. J., Saper, M. A., Samraoui, B., Bennet, W. S., Strominger, J. L., and Wiley, D. C. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature 329: 512–518, 1987b
Bjorkman, P. J. and Parham, P. Structure, function, and diversity of class I major histocompatibility complex molecules. Annu Rev Biochem 59: 253–288, 1990
Black, F. L. Why did they die? Science 258: 1739–1740, 1992
Bodmer, J. G., marsh, S. G. E., Albert, E. D., Bodmer, W. F., Dupont, B., Erlich, H. A., Mach, B., Mayr, W. R., Parham, P., Sasazuki, T., Schreuder, G. M. Th., Strominger, J., Svejgaard, A., and Terasaki, P. I. Nomenclature for factors of the HLA system, 1994. Tissue Antigens 44: 1–18, 1994
Chen, Z. W., McAdam, S. N., Hughes, A. L., Dogan, A. L., Letvin, N. L., and Watkins, D. I. Molecular cloning of orangutan and gibbon MHC class I cDNAs: the HLA-A and -B loci diverged over 30 million years ago. J Immunol 148: 2547–2554, 1992
Domena, J. D., Johnston-Dow, L., and Parham, P. The B *4002 allele encodes the B61 antigen: B40* is identical to B61. Tissue Antigens 40: 254–256, 1992
Erickson, E. E., Barth, H. A., and Chaffe, F. H. Area Handbook for Ecuador, U. S. Government Printing Office, Washington, D. C., 1966
Fan, W., Kasahara, M., Gutknecht, J., Klein, D., Mayer, W. E., Jonker, M., Klein, J. Shared class II MHC polymorphisms between humans and chimpanzees. Hum Immunol 26: 107–121, 1989
Fawcett, T. W., and Bartlett, S. G. An effective method for eliminating “artifact banding” when sequencing double-stranded DNA templates. Biotechniques 9: 46–47, 1990
Garber, T. L., Hughes, A. L., Watkins, D. I., and Templeton, J. W. Evidence for atleast three transcribed BoLA class I loci. Immunogenetics 39: 257–265, 1994
Garrett, T. P. J., Saper, M. A., Bjorkman, P. J., Strominger, J. L., and Wiley, D. C. Specificity pockets for the side chains of peptide antigens in HLA-Aw68. Nature 342: 692–696, 1989
Geluk, A., Elferink, D. G., Slierendregt, B. L., Meijgaarden, K. E., van de Vries, R. R. P., Ottenhoff, T. H. M., Bontrop, R. E. Evolutionary conservation of major histocompatibility complex-DR/peptide/ T cell interactions in primates. J Exp Med 177: 979–987, 1993
Greenberg, J. H., Turner, C. G., and Zegura, S. L. The settlement of the Americas: a comparison of the linguistic, dental, and genetic evidence. Curr Anthropol 27: 477–497, 1986
Greenberg, J. H. Language in the Americas, Stanford University Press, Stanford, 1987
Gyllensten, U. B. and Erlich, H. A. Ancient roots for polymorphism at the HLA-DQa locus in primates. Proc Natl Acad Sci USA 86: 9986–9990, 1989
Gyllensten, U. B., Lashkari, D., and Erlich, H. A. Allelic diversification at the class II DQB locus of the mammalian major histocompatibility complex. Proc Natl Acad Sci USA 87: 1835–1839, 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 USA 88: 3686–3690, 1991
Hildebrand, W. H., Domena, J. D., Shen, S. Y., Lau, M., Terasaki, P. I., Bunce, M., Marsh, S. G. E., Guttridge, M. G., Bias, W. B., and Parham, P. HLA-B15: a widespread and diverse family of HLA-B alleles. Tissue Antigens 43: 209–218, 1994
Hill, A. V. S., Allsopp, C. E. M., Kwiatkowski, D., Anstey, N. W., Twumasi, P., Rowe, P. A., Benneyt, S., Brewster, D., McMichael, A. J., and Greenwood, B. M. Common West African HLA antigens are associated with protection from severe malaria. Nature 352: 595–600, 1991
Hill, A. V. S., Elvin, J., Willis, A. C., Aidoo, M., Allsopp, C. E. M., Gotch, F. M., Gao, X. M., Takiguchi, M., Greenwood, B. M., Townsend, A. R. M., McMichael, A. J., and Whittle, H. C. Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature 360: 433–439, 1992
Horai, S., Kondo, R., Nakagawa-Hattori, Y., Hayashi, S., Sonoda, S., and Tajima, K. Peopling of the Americas, founded by four major lineages of mitochondrial DNA. Mol Biol Evol 10: 23–47, 1993
Hughes, A. L. and Nei, M. Pattern of nucleotide substitution at major histocompatibility complex loci reveals overdominant selection. Nature 335: 167–170, 1988
Hughes, A. L. and Nei, M. Nucleotide substitution at major histocompatibility complex class II loci: evidence for overdominant selection. Proc Natl Acad Sci USA 86: 958–962, 1989
Hughes, A. L., Hughes, M. K., and Watkins, D. I. Contrasting roles of interallelic recombination at the HLA-A and HLA-B loci. Genetics 133: 669–680, 1993
Imanishi, T., Akaza, T., Kimura, A., Tokonaga, K., Gojobori, T. Allele and haplotype frequencies for HLA and complement loci in various ethnic groups. In K. Tsuji, M. Aizawa, and T. Sasazui (eds): HLA 1991. Proceedings of the eleventh International Histocompatibility Workshop and Conference, Vol. 1, pp. 1065–1220, Oxford University, Press, Oxford, 1992
Kato, N., Karaki, S., Kashiwase, K., Müller, C., Akaza, T., Juji, T., Kano, K., and Takiguchi, M. Molecular analysis of HLA-B39 subtypes. Immunogenetics 37: 212–216, 1993
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 a
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 b
Klein, J. Natural History of the Major Histocompatibility Complex, Wiley, New York, 1986
Klein, J. Origin of the major histocompatibility complex polymorphism: The transspecies hypothesis. Hum Immunol 19: 155,1987
Kostyu, D. D. and Amos, D. B. Mysteries of the Amerindians. Tissue Antigens 16: 111–123, 1981
Lawlor, D. A., Ward, F. E., Ennis, P. D., Jackson, A. P., and Parham, P. HLA-A and -B polymorphism predate the divergence of humans and chimpanzees. Nature 335: 268–271, 1988
Ling, L., Watanabe, Y., Tokunaga, K., Kuwata, S., Kohsaka, T., Akaza, T., and Juji, T. A Common Japanese haplotype HLA-A26-Cw3-DR9-DQ3 carries HLA-B *4002. Tissue Antigens 40: 257–260, 1992
Madden, D. R., Gorga, J. C., Strominger, J. L., and Wiley, D. C. The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation. Nature 353: 321–325, 1991
Markow, T., Hedrick, P. W., Zuerlin, K., Danilovs, J., Martin, J., Vyvial, T., and Armstrong, C. HLA polymorphism in the Havasupai: evidence for balancing selection. Am J Hum Genet 53: 943–952, 1993
Mayer, W. E., Jonker, M., Klein, D., Ivanyi, P., van Seventer, G., and Klein, J. Nucleotide sequences of chimpanzee MHC class I alleles: evidence for transspecies mode of evolution. EMBO J 7: 2765–2774, 1988
McAdam, S. N., Boyson, J. E., Liu, X., Garber, T. L., Hughes, A. L., Bontrop, R. E., and Watkins, D. I. A uniquely high level of recombination at the HLA-B locus. Proc Natl Acad Sci, USA 91: 5893–5897, 1994
McAdam, S. N., Boyson, J. E., Liu, X., Garber, T. L., Hughes, A. L., Bontrop, R. E. and Watkins, D. I. Chimpanzee major histocompatibility complex class I A locus alleles are related to only one of the six families of human A locus alleles. J Immunol, in press
McCrea, K. W., Marrs, C. F., and Gilsdorf, J. R. Gel compression and artifact banding can be resolved in the same DNA sequencing reaction. Biotechniques 15: 843–844, 1993
Melton, D. A., Krieg, P. A., Rebagliati, M. R., Maniatis, T., Zinn, K., and Green, M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing bacteriophage SP6 promotor. Nucleic Acids Res 12: 7035–7056, 1984
Miller, S. A., Dykes, K. K., and Plesky, H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16: 1215, 1988
Miller, M. D., Yamamoto, H., Hughes, A. L., Watkins, D. I., and Letvin, N. L. Definition of an epitope and MHC class I molecules recognized by gag specific cytotoxic T lymphocytes in SIV macinfected rhesus monkeys. J Immunol 147: 320–329, 1991
Ooba, T., Hayashi, H., Karaki, S., Tanabe, M., Kano, K., and Takiguchi, M. The structure of HLA-B35 suggests that it is derived from HLA-Bw58 by two genetic mechanisms. Immunogenetics 30: 76–80, 1989
Parham, P. Evolution of class I HLA polymorphism: selection and drift. In K. Tsuji, M. Aizawa, and T. Sasazuki (eds): HLA 1991. Proceedings of the Eleventh International Histocompatibility Workshop and Conference; Vol. 2, pp. 72–82, Oxford University Press, Oxford, 1992
Parham, P., Lawlor, D. A., Lomen, C. E., and Ennis, P. D. Diversity and diversification of HLA-A, B, C alleles. J Immunol 142: 3937–3950, 1989
Petzl-Erler, M. L., Luz, R., and Sotomaior, V. S. The HLA polymorphism of two distinctive South-American Indian tribes: the Kaingang and the Guarani. Tissue Antigens 41: 227–237, 1993
Pohla, H., Kuon, W., Tabaczewski, P., Doerner, C., and Weiss, E. H. Allelic variation in HLA-B and HLA-C sequences and the evolution of the HLA-B alleles. Immunogenetics 29: 297–307, 1989
Rickards, O., Tartaglia, M., Martínez-Labarga, C., and De Stefano, G. F. Genetic characterization of the Cayapa Indians of Ecuador and their genetic relationships to other Native American populations. Hum Biol 66: 299–322, 1994
Salter, R. D., Norment, A. M., Chen, B. P., Clayberger, C., Krensky, A. M., Littman, D. R., and Parham, P. Polymorphism in the alpha 3 domain of HLA-A molecules affects binding to CD8. Nature 338: 345–347, 1989
Sanger, F., Nicklen, S., and Coulson, A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74: 5463–5467, 1977
Saper, M. A., Bjorkman, P. J., and Wiley, D. C. Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 Å resolution. J Mol Biol 219: 277–319, 1991
Schanfield, M. S. Immunoglobulin allotypes (GM and KM) indicate multiple founding populations of Native Americans: evidence of at least four migrations to the New World. Hum Biol 64: 381–402, 1992
Schwartz, R. H. T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu Rev Immunol 3: 237–261, 1985
Slierendregt, B. L., van Noort, J. Y., Bakas, R. M., Otting, N., Jonker, M., and Bontrop, R. E. Evolutionary stability of transspecies major histocompatibility complex class II DRB lineages in humans and rhesus monkeys. Hum Immunol 35: 29–39, 1992
Stinson, S. Physical growth of Ecuadorian Chachi Amerindians. Am J Hum Biol 1: 697–707, 1989
Takahata, N. and Nei, M. Allelic genealogy under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci. Genetics 124: 967–978, 1990
Theiler, G., Pando, M., Delfino, J. M., Takiguchi, M., and Satz, M. L. Isolation and characterization of two new functional subtypes of HLA-B35. Tissue Antigens 41: 143–147, 1993
Titus-Trachtenberg, E. A., Rickards, O., De Stephano, G. F., and Erlich, H. Analysis of HLA class II haplotypes in the Cayapa Indians of Ecuador: a novel DRB1 allele reveals evidence for convergent evolution and balancing selection at position 86. Am J Hum Genetics 55: 160–167, 1994
Townsend, A. R. M., Rothbard, J., Gotch, F. M., Bahadur, G., Wraith, D., and McMichael, A. J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44: 959–968, 1986
Unanue, E. R., Antigen-presenting function of the macrophage. Annu Rev Immunol 2: 395–428, 1984
Watkins, D. I., McAdam, S. N., Liu, X., Strang, C. R., Milford, E. L., Levine, C. G., Garber, T. L., Dogon, A. L., Lord, C. I., Ghim, S. H., Troup, G. M., Hughes, A. L., and Letvin, N. L. New recombinant HLA-B alleles in a tribe of South Amerindians indicate rapid evolution of MHC class I loci. Nature 357: 329–333, 1992
Williams, R. C. and McAuley, J. E. HLA class I variation controlled for genetic admixture in the Gila River Indian community of Arizona: a model for the Paleo-Indians. Hum Immunol 33: 39–46, 1992
Williams, R. C., Steinberg, A. G., Gershowitz, H., Bennett, P. H., Knowler, W. C., Pettitt, D. J., Butler, W., Baird, R., Dowda-Rea, L., Burch, T. A., Morse, H. G., and Smith, C. G. GM allotypes in Native Americans: evidence for three distinct migrations across the Bering land bridge. Am J Phys Anthropol 66: 1–19, 1985
Yoshida, M., Kimura, A., Numana, F., and Sasazuki, T. Polymerase-chain-reaction-based analysis of polymorphism in the HLA-B gene. Hum Immunol 34: 257–266, 1992
Zemmour, J. and Parham, P. HLA class I nucleotide sequences, 1992. Tissue Antigens 40: 221–228, 1992
Zinkernagel, R. M. and Doherty, P. C. Restriction of T cell mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semisyngeneic system. Nature 248: 701–702, 1974
Author information
Authors and Affiliations
Additional information
The names listed for these sequences were officially assigned by the WHO nomenclature Committee in September 1994, B *3905, and November 1994, B *1522, B*3906, and B *3907. This follows the agreed policy that, subject to the conditions stated in the most recent Nomenclature Report (Bodmer et al. 1994), names will be assigned to the new sequences as they are identified. Lists of such new names will be published in the following WHO Nomenclature Report.
Rights and permissions
About this article
Cite this article
Garber, T.L., Butler, L.M., Trachtenberg, E.A. et al. HLA-B alleles of the Cayapa of Ecuador: new B39 and B15 alleles. Immunogenetics 42, 19–27 (1995). https://doi.org/10.1007/BF00164983
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00164983