, Volume 56, Issue 10, pp 683–695 | Cite as

Comparative genomics of major histocompatibility complexes



The major histocompatibility complex (MHC) is a gene dense region found in all jawed vertebrates examined to date. The MHC contains a high percentage of immune genes, in particular genes involved in antigen presentation, which are generally highly polymorphic. The region plays an important role in disease resistance. The clustering of MHC genes could be advantageous for co-evolution or regulation, and its study in many species is desirable. Even though some linkage of MHC genes is apparent in all gnathostomes, the genomic organization can differ greatly by species, suggesting rapid evolution of MHC genes after divergence from a common ancestor. Previous reviews of comparative MHC organization have been written when relatively fragmentary sequence and mapping data were available on many species. This review compares maps of MHC gene orders in commonly studied species, where extensive sequencing has been performed.



We would like to thank Martin Flajnik and Pierre Pontarotti for useful comments regarding this review.

Supplementary material

Fig. 1 (high resolution)

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  1. Abi-Rached L, Gilles A, Shiina T, Pontarotti P, Inoko H (2002) Evidence of en bloc duplication in vertebrate genomes. Nat Genet 31:100–105CrossRefPubMedGoogle Scholar
  2. Adams EJ, Parham P (2001a) Genomic analysis of common chimpanzee major histocompatibility complex class I genes. Immunogenetics 53:200–208CrossRefPubMedGoogle Scholar
  3. Adams EJ, Parham P (2001b) Species-specific evolution of MHC class I genes in the higher primates. Immunol Rev 183:41–64CrossRefPubMedGoogle Scholar
  4. Adams EJ, Thomson G, Parham P (1999) Evidence for an HLA-C like locus in the orangutan Pongo pygmaeus. Immunogenetics 49:865–871CrossRefPubMedGoogle Scholar
  5. Adams EJ, Cooper S, Parham P (2001) A novel, nonclassical MHC class I molecule specific to the common chimpanzee. J Immunol 167:3858–3869PubMedGoogle Scholar
  6. Aguado B, Milner CM, Campbell RD (1996) Genes of the MHC class III region and the functions of the proteins they encode. In: Browning M, McMichael A (eds) HLA and MHC: genes, molecules, and functions. Bios, Oxford, pp 39–76Google Scholar
  7. Amadou C (1999) Evolution of the MHC class I region: the framework hypothesis. Immunogenetics 49:362–367CrossRefPubMedGoogle Scholar
  8. Amills M, Ramiya V, Norimine J, Lewin HA (1998) The major histocompatibility of ruminants. Rev Sci Tech 17:108–120PubMedGoogle Scholar
  9. Anzai T, Shiina T, Kimura N, Yanagiya K, Kohara S, Shigenari A, Yamagata T, Kulski JK, Naruse TK, Fujimori Y, Fukuzumi Y, Yamazaki M, Tashiro H, Iwamoto C, Umehara Y, Imanishi T, Meyer A, Ikeo K, Gojobori T, Bahram S, Inoko H (2003) Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions/deletions as the major path to genomic divergence. Proc Natl Acad Sci USA 100:7708–7713CrossRefPubMedGoogle Scholar
  10. Ballingall KT, Ellis SA, MacHugh ND, Archibald SD, McKeever DJ (2004) The DY genes of the cattle MHC: expression and comparative analysis of an unusual class II MHC gene pair. Immunogenetics 55:748–755CrossRefPubMedGoogle Scholar
  11. Band M, Larson JH, Womack JE, Lewin HA (1998) A radiation hybrid map of BTA23: identification of a chromosomal rearrangement leading to separation of the cattle MHC class II subregions. Genomics 53:269–275CrossRefPubMedGoogle Scholar
  12. Bartl S, Weissman IL (1994) Isolation and characterization of major histocompatibility complex class IIB genes from the nurse shark. Proc Natl Acad Sci USA 91:262–266Google Scholar
  13. Bartl S, Baish MA, Flajnik MF, Ohta Y (1997) Identification of class I genes in cartilaginous fish, the most ancient group of vertebrates displaying an adaptive immune response. J Immunol 159:6097–6104PubMedGoogle Scholar
  14. Beck S, Trowsdale J (2000) The human major histocompatibility complex: lessons from the DNA sequence. Annu Rev Genomics Hum Genet 1:117–137CrossRefGoogle Scholar
  15. Beck S, Kelly A, Radley E, Khurshid F, Alderton RP, Trowsdale J (1992) DNA sequence analysis of 66 kb of the human MHC class II region encoding a cluster of genes for antigen processing. J Mol Biol 228:433–441PubMedGoogle Scholar
  16. Belov K, Lam MKP, Hellman L, Colgan DJ (2003) Evolution of the major histocompatibility complex: isolation of class II beta cDNAs from two monotremes, the platypus and the short-beaked echidna. Immunogenetics 55:402–411CrossRefPubMedGoogle Scholar
  17. Benacerraf B (1981) Role of MHC gene products in immune regulation. Science 212:1229–1238Google Scholar
  18. Bingulac-Popovic J, Figueroa F, Sato A, Talbot WS, Johnson SL, Gates M, Postlethwait JH, Klein J (1997) Mapping of MHC class I and class II regions to different linkage groups in the Zebrafish, Danio rerio. Immunogenetics 46:129–134CrossRefPubMedGoogle Scholar
  19. Boyson JE, Shufflebotham C, Cadavid LF, Urvater JA, Knapp LA, Hughes AL, Watkins DL (1996) The MHC class I genes of the Rhesus monkey. Different evolutionary histories of MHC class I and II genes in primates. J Immunol 156:4656–4665PubMedGoogle Scholar
  20. Browning TL, Belov K, Miller RD, Eldridge MDB (2004) Molecular cloning and characterization of the polymorphic MHC class II DBB from the tammar wallaby (Macropus eugenii). Immunogenetics 55:791–795CrossRefPubMedGoogle Scholar
  21. Cadavid LF, Shufflebotham C, Ruiz FJ, Yeager M, Hughes AL, Watkins DL (1997) Evolutionary instability of the major histocompatibility complex class I loci in new world primates. Proc Natl Acad Sci USA 94:14536–14541Google Scholar
  22. Cadavid LF, Mejia BE, Watkins DL (1999) MHC class I genes in a new world primate, the cotton-top tamarin (Saguinus oedipus), have evolved by an active process of loci turnover. Immunogenetics 49:196–205CrossRefPubMedGoogle Scholar
  23. Carrington M, Bontrop RE (2002) Effects of MHC class I on HIV/SIV disease in primates. AIDS 16:S105–S114PubMedGoogle Scholar
  24. Castro LFC, Furlong RF, Holland PWH (2004) An antecedent of the MHC-linked genomic region in Amphioxus. Immunogenetics 55:782–784CrossRefPubMedGoogle Scholar
  25. Cattley SK, Longman N, Dawkins RL, Gaudieri S, Kulski JK, Leelayuwat C (1999) Phylogenetic analysis of primate MIC (PERB11) sequences suggests that the representation of the gene family differs in different primates: comparison of MIC (PERB11) and C4. Eur J Immunogenet 26:233–238CrossRefPubMedGoogle Scholar
  26. Chardon P, Renard C, Gaillard CR, Vaiman M (2000) The porcine major histocompatibility complex and paralagous regions: a review. Genet Sel Evol 32:109–128CrossRefPubMedGoogle Scholar
  27. Clark MS, Pontarotti P, Gilles A, Kelly A, Elgar G (2000) Identification and characterization of a β proteasome subunit cluster in the Japanese pufferfish (Fugu rubripes). J Immunol 165:4446–4452Google Scholar
  28. Clark MS, Shaw L, Kelly A, Snell P, Elgar G (2001) Characterization of the MHC class I region of the Japanese pufferfish (Fugu rubripes). Immunogenetics 52:174–185Google Scholar
  29. Courtet M, Flajnik MF, Du Pasquier L (2001) Major histocompatibility complex and immunoglobulin loci visualized by in situ hybridization on Xenopus chromosomes. Dev Comp Immunol 25:149–157CrossRefPubMedGoogle Scholar
  30. Danchin EGJ, Abi-Rached L, Gilles A, Pontarotti P (2003) Conservation of the MHC-like region throughout evolution. Immunogenetics 55:141–148Google Scholar
  31. Danchin EGJ, Vitiello V, Vienne A, Richard O, Gouret P, McDermott MF, Pontarotti P (2004) The major histocompatibility complex origin. Immunol Rev 198:216–232CrossRefPubMedGoogle Scholar
  32. Dausset J (1959) Iso-leuco-anticorps. Acta Haematol 20:156Google Scholar
  33. Delarbre C, Jaulin C, Kourilsky P, Gachelin G (1992) Evolution of the major histocompatibility complex: a hundred-fold amplification of MHC class I genes in the African pigmy mouse Nannomys setulosus. Immunogenetics 37:29–38Google Scholar
  34. De Tomaso AW, Weissman IL (2003) Initial characterization of a protochordate histocompatibility locus. Immunogenetics 55:480–490Google Scholar
  35. De Tomaso AW, Weissman IL (2004) Evolution of a protochordate allorecognition locus. Science 303:977Google Scholar
  36. Edwards SV, Grahn M, Potts WK (1995a) Dynamics of MHC evolution in birds and crocodilians: amplification of class II genes with degenerate primers. Mol Ecol 4:719–729PubMedGoogle Scholar
  37. Edwards SV, Wakeland EK, Potts WK (1995b) Contrasting histories of avian and mammalian MHC genes revealed by class II B sequences from songbirds. Proc Natl Acad Sci USA 92:12200–12204Google Scholar
  38. Edwards SV, Gasper J, Garrigan D, Martindale D, Koop BF (2000) A 39-kb sequence around a blackbird MHC class II gene: ghost of selection past and songbird genome architecture. Mol Biol Evol 17:1384–1395PubMedGoogle Scholar
  39. Ellis SA, Ballingall KT (1999) Cattle MHC: evolution in action? Immunol Rev 167:159–168Google Scholar
  40. Escriva H, Manzon L, Youson J, Laudet V (2002) Analysis of lamprey and hagfish genes reveals a complex history of gene duplications during early vertebrate evolution. Mol Biol Evol 19:1440–1450PubMedGoogle Scholar
  41. Fagan MB, Weissman IL (1998) Linkage analysis of HSP70 genes and historecognition locus in Botryllus schlosseri. Immunogenetics 47:468–476Google Scholar
  42. Fernández-Busquets X, Burger MM (1999) Cell adhesion and histocompatibility in sponges. Microsc Res Tech 44:204–218CrossRefPubMedGoogle Scholar
  43. Figueroa F, Mayer WE, Sato A, Zaleska-Rutczynska Z, Hess B, Tichy H, Klein J (2001) MHC class I genes of swordtail fishes, Xiphophorus: variation in the number of loci and existence of ancient gene families. Immunogenetics 53:695–708Google Scholar
  44. Flajnik MF (2004) Immunology: another manifestation of GOD. Nature 430:157–158CrossRefPubMedGoogle Scholar
  45. Flajnik MF, Kasahara M (2001) Comparative genomics of the MHC: glimpses into the evolution of the adaptive immune system. Immunity 15:351–362CrossRefPubMedGoogle Scholar
  46. Flajnik MF, Kasahara M, Shum BP, Salter-Cid L, Taylor E, Du Pasquier L (1993) A novel type of class I gene organization in vertebrates: a large family of non-MHC-linked class I genes is expressed at the RNA level in the amphibian Xenopus. EMBO J 12:4385–4396PubMedGoogle Scholar
  47. Flajnik MF, Ohta Y, Namikawa-Yamada C, Nonaka M (1999) Insight into the primordial MHC from studies in ectothermic vertebrates. Immunol Rev 167:59–67Google Scholar
  48. Flügge P, Zimmermann E, Hughes AL, Gunther E, Walter L (2002) Characterization and phylogenetic relationship of prosimian MHC class I genes. J Mol Evol 55:768–775CrossRefPubMedGoogle Scholar
  49. Frangoulis B, Park I, Guillemot F, Severac V, Auffray C, Zoorob R (1999) Identification of the tapasin gene in the chicken major histocompatibility complex. Immunogenetics 49:328–337Google Scholar
  50. Freeman-Gallant CR, Johnson EM, Saponara F, Stanger M (2002) Variation at the major histocompatibility complex in savannah sparrows. Mol Ecol 11:1125–1130Google Scholar
  51. Gebe JA, Swanson E, Kwok WW (2002) HLA class II peptide-binding and autoimmunity. Tissue Antigens 59:78–87CrossRefPubMedGoogle Scholar
  52. Geller R, Adams EJ, Guethlein LA, Little A-M, Madrigal AJ, Parham P (2002) Linkage of Patr-AL to Patr-A and -B in the major histocompatibility complex of the common chimpanzee (Pan troglodytes). Immunogenetics 54:212–215Google Scholar
  53. Geraghty DE, Daza R, Williams LM, Vu Q, Ishitani A (2002) Genetics of the immune response: identifying immune variation within the MHC and throughout the genome. Immunol Rev 190:69–85Google Scholar
  54. Glynne R, Powis SH, Beck S, Kelly A, Kerr L-A, Trowsdale J (1991) A proteasome-related gene between the two ABC transporter loci in the class II region of the human MHC. Nature 353:357–360CrossRefPubMedGoogle Scholar
  55. Go Y, Satta Y, Kawamoto Y, Rakotoarisoa G, Randrianjafy A, Koyama N, Hirai H (2003) Frequent segmental sequence exchanges and rapid gene duplication characterize the MHC class I genes in lemurs. Immunogenetics 55:450–461Google Scholar
  56. Gorer PA, Lyman S, Snell GD (1948) Studies on the genetic and antigenic basis of tumour transplantation: linkage between a histocompatibility gene and “Fused” in mice. Proc R Soc Lond 135:499–505Google Scholar
  57. Grossberger D, Parham P (1992) Reptilian class I major histocompatibility complex genes reveal conserved elements in class I structure. Immunogenetics 36:166–174Google Scholar
  58. Gruen JR, Weissman SM (1997) Evolving views of the major histocompatability complex. Blood 90:4252–4265PubMedGoogle Scholar
  59. Guillemot F, Billault A, Pourquie O, Behar G, Chausse AM, Zoorob R, Kreibich G, Auffray C (1988) A molecular map of the chicken major histocompatibility complex: the class II beta genes are closely linked to the class I genes and the nucleolar organizer. EMBO J 7:2775–2785PubMedGoogle Scholar
  60. Gustafson AL, Tallmadge RL, Ramlachan N, Miller D, Bird H, Antczak DF, Raudsepp T, Chowdhary BP, Skow LC (2003) An ordered BAC contig map of the equine major histocompatibility complex. Cytogenet Genome Res 102:189–195CrossRefPubMedGoogle Scholar
  61. Hansen JD, Strassburger P, Du Pasquier L (1996) Conservation of an alpha 2 domain within the teleostean world, MHC class I from the rainbow trout Oncorhynchus mykiss. Dev Comp Immunol 20:417–425CrossRefPubMedGoogle Scholar
  62. Hansen JD, Strassburger P, Thorgaard GH, Young WP, Du Pasquier L (1999) Expression, linkage, and polymorphism of MHC-related genes in rainbow trout, Oncorhynchus mykiss. J Immunol 163:774–786Google Scholar
  63. Herberg JA, Beck S, Trowsdale J (1998) TAPASIN, DAXX, RGL2, HKE2 and four new genes (BING1, 3 to 5) form a dense cluster at the centromeric end of the MHC. J Mol Biol 277:839–857CrossRefPubMedGoogle Scholar
  64. Holling T, Schooten E, van Den Elsen PJ (2004) Function and regulation of MHC class II molecules in T-lymphocytes: of mice and men. Hum Immunol 65:282–290CrossRefPubMedGoogle Scholar
  65. Holmes EC, Ellis SA (1999) Evolutionary history of MHC class I genes in the mammalian order Perissodactyla. J Mol Evol 49:316–324PubMedGoogle Scholar
  66. Horton R, Wilming LG, Rand V, Lovering RC, Bruford EA, Khodiyar VK, Talbot CC, Wright MW, Wain HM, Trowsdale J, Ziegler A, Beck S (2004) Gene map of the extended human major histocompatibility complex. Nat Genet Rev (in press)Google Scholar
  67. Houlden BA, Greville WD, Sherwin WB (1996) Evolution of MHC class I loci in marsupials: characterization of sequences from koala (Phascolarctos cinereus). Mol Biol Evol 13:1119–1127PubMedGoogle Scholar
  68. Hughes AL (1995) Origin and evolution of HLA class I pseudogenes. Mol Biol Evol 12:247–258PubMedGoogle Scholar
  69. Hughes AL, Nei M (1989) Evolution of the major histocompatibility complex: independent origin of nonclassical class I genes in different groups of mammals. Mol Biol Evol 6:559–579PubMedGoogle Scholar
  70. Hurt P, Walter L, Sudbrak R, Klages S, Muller I, Shiina T, Inoko H, Lehrach H, Günther E, Reinhardt R, Himmelbauer H (2004) The genomic sequence and comparative analysis of the rat major histocompatibility complex. Genome Res 14:631–639CrossRefPubMedGoogle Scholar
  71. Ishii T, Hirota J, Mombaerts P (2003) Combinatorial coexpression of neural and immune multigene families in mouse vomeronasal sensory neurons. Curr Biol 13:394–400CrossRefPubMedGoogle Scholar
  72. Joly E, Le Rolle A-F, Gonzalez AL, Mehling B, Stevens J, Coadwell WJ, Hunig T, Howard JC, Butcher GW (1998) Co-evolution of rat TAP transporters and MHC class I RT1-A molecules. Curr Biol 8:169–172CrossRefPubMedGoogle Scholar
  73. Juul-Madsen HR, Dalgaard TS, Guldbrandtsen B, Salomonsen J (2000) A polymorphic major histocompatibility complex class II-like locus maps outside of both the chicken B-system and Rfp-Y system. Eur J Immunogenet 27:63–71CrossRefPubMedGoogle Scholar
  74. Kasahara M (1999) Genome dynamics of the major histocompatibility complex: insights from genome paralogy. Immunogenetics 50:134–145Google Scholar
  75. Kasahara M (2000) Major histocompatibility complex: evolution, structure, and function. Springer, TokyoGoogle Scholar
  76. Kasahara M, Vazquez M, Sato K, McKinney EC, Flajnik MF (1992) Evolution of the major histocompatibility complex: isolation of class II A cDNA clones from the cartilaginous fish. Proc Natl Acad Sci USA 89:6688–6692Google Scholar
  77. Kasahara M, Hayashi M, Tanaka K, Inoko H, Sugaya K, Ikemura T, Ishibashi T (1996) Chromosomal localization of the proteasome Z subunit gene reveals an ancient chromosomal duplication involving the major histocompatibility complex. Proc Natl Acad Sci USA 93:9096–9101Google Scholar
  78. Kasahara M, Watanabe Y, Sumasu M, Negata T (2002) A family of MHC class I-like genes located in the vicinity of the mouse leukocyte receptor complex. Proc Natl Acad Sci USA 99:13687–13692Google Scholar
  79. Kasahara M, Suzuki T, Du Pasquier L (2004) On the origins of the adaptive immune system: novel insights from invertebrates and cold-blooded vertebrates. Trends Immunol 25:105–111CrossRefPubMedGoogle Scholar
  80. Katsanis N, Fitzgibbon J, Fisher EMC (1996) Paralogy mapping: identification of a region in the human MHC triplicated onto human chromosomes 1 and 9 allows the prediction and isolation of novel PBX and NOTCH loci. Genomics 35:101–108CrossRefPubMedGoogle Scholar
  81. Kaufman J (2002) The origins of the adaptive immune system: whatever next? Nat Immunol 3:1124–1125Google Scholar
  82. Kaufman J, Skjoedt K, Salomonsen J (1990) The MHC molecules of nonmammalian vertebrates. Immunol Rev 113:83–117PubMedGoogle Scholar
  83. Kaufman J, Volk H, Wallny HJ (1995) A “Minimal Essential MHC” and an “Unrecognized MHC”: two extremes in selection for polymorphism. Immunol Rev 143:63–88PubMedGoogle Scholar
  84. Kaufman J, Milne S, Gobel TWF, Walker BA, Jacob JP, Auffray C, Zoorob R, Beck S (1999a) The chicken B locus is a minimal major histocompatibility complex. Nature 401:923–925CrossRefPubMedGoogle Scholar
  85. Kaufman J, Jacob JP, Shaw I, Walker B, Milne S, Beck S, Salomonsen J (1999b) Gene organization determines evolution of function in the chicken MHC. Immunol Rev 167:101–117Google Scholar
  86. Kelly A, Powis SH, Glynne R, Radley E, Beck S, Trowsdale J (1991) Second proteasome-related gene in the human MHC class II region. Nature 353:667–668CrossRefPubMedGoogle Scholar
  87. Khalturin K, Becker M, Rinkevich B, Bosch TCG (2003) Urochordates and the origin of natural killer cells: identification of a CD94/NKR-P1-related receptor in blood cells of Botryllus. Proc Natl Acad Sci 100:622–627Google Scholar
  88. Klein J (1976) Evolution and function of the major histocompatibility complex: facts and speculations. In: Gotze D (ed) The major histocompatibility system in man and animals. Springer, New York Berlin Heidelberg, pp 339–378Google Scholar
  89. Klein J, Sato A (1998) Birth of the major histocompatibility complex. Scand J Immunol 47:199–209CrossRefPubMedGoogle Scholar
  90. Kobari F, Sato K, Shum BP, Tochinai S, Katagiri M, Ishibashi T, Du Pasquier L, Flajnik MF, Kasahara M (1995) Exon–intron organization of Xenopus class II beta chain genes. Immunogenetics 42:376–385Google Scholar
  91. Kulski JK, Shiina T, Anzai T, Kohara S, Inoko H (2002) Comparative genomic analysis of the MHC: the evolution of class I duplication blocks, diversity, and complexity from shark to man. Immunol Rev 190:95–122CrossRefPubMedGoogle Scholar
  92. Kumánovics A, Takada T, Lindahl KF (2003) Genomic organization of the mammalian MHC. Annu Rev Immunol 21:629–657CrossRefPubMedGoogle Scholar
  93. Kuroda N, Naruse K, Shima A, Nonaka M, Sasaki M (2000) Molecular cloning and linkage analysis of complement C3 and C4 genes of the Japanese medaka fish. Immunogenetics 51:117–128Google Scholar
  94. Kuroda N, Figueroa F, O’hUigin C, Klein J (2002) Evidence that the separation of MHC class II from class I loci in the zebrafish, Danio rerio, occurred by translocation. Immunogenetics 54:418–430CrossRefPubMedGoogle Scholar
  95. Laird DJ, De Tomaso AW, Cooper MD, Weissman IL (2000) 50 Million years of chordate evolution: seeking the origins of adaptive immunity. Proc Natl Acad Sci USA 97:6924–6926Google Scholar
  96. Lambracht-Washington D, Lindahl KF (2004) Active MHC class Ib genes in rat are pseudogenes in the mouse. Immunogenetics 56:118–121Google Scholar
  97. Lawlor DA, Warren E, Taylor P, Parham P (1991) Gorilla class I major histocompatibility complex alleles: comparison to human and chimpanzee class I. J Exp Med 174:1491–1509CrossRefPubMedGoogle Scholar
  98. Lienert K, Parham P (1996) Evolution of MHC class I genes in higher primates. Immunol Cell Biol 74:349–356PubMedGoogle Scholar
  99. Loconto J, Papes F, Chang E, Stowers L, Jones EP, Takada T, Kumanovics A, Lindahl KF, Dulac C (2003) Functional expression of murine V2R pheromone receptors involves selective association with the M10 and M1 families of MHC class Ib molecules. Cell 112:607–618CrossRefPubMedGoogle Scholar
  100. Madden DR (1995) The three-dimensional structure of peptide-MHC complexes. Annu Rev Immunol 13:587–622CrossRefPubMedGoogle Scholar
  101. Magor BG, De Tomaso AW, Rinkevich B, Weissman IL (1999) Allorecognition in colonial tunicates: protection against predatory cell lineages. Immunol Rev 167:69–79Google Scholar
  102. Malaga-Trillo E, Zaleska-Rutczynska Z, McAndrew B, Vincek V, Figueroa F, Sultmann H, Klein J (1998) Linkage relationships and haplotype polymorphism among cichlid MHC class II B loci. Genetics 149:1527–1537PubMedGoogle Scholar
  103. Matsuo MY, Asakawa S, Shimizu N, Kimura H, Nonaka M (2002) Nucleotide sequence of the MHC class I genomic region of a teleost, the medaka (Oryzias latipes). Immunogenetics 53:930–940CrossRefPubMedGoogle Scholar
  104. Mayer WE, Jonker M, Klein D, Ivanyi P, van Seventer G, Klein J (1988) Nucleotide sequences of chimpanzee MHC class I alleles: evidence for trans-species mode of evolution. EMBO J 7:2765–2774PubMedGoogle Scholar
  105. McConnell TJ, Godwin UB, Cuthbertson BJ (1998a) Expressed major histocompatibility complex class II loci in fishes. Immunol Rev 166:294–300PubMedGoogle Scholar
  106. McConnell TJ, Godwin UB, Norton SF, Nairn RS, Kazianis S, Morizot DC (1998b) Identification and mapping of two divergent, unlinked major histocompatibility complex class II B genes in Xiphophorus fishes. Genetics 149:1921–1934PubMedGoogle Scholar
  107. MHC Sequencing Consortium (1999) Complete sequence and gene map of a human major histocompatibility complex. Nature 401:921–923Google Scholar
  108. Michalova V, Murray BW, Sultmann H, Klein J (2000) A contig map of the MHC class I genomic region in the zebrafish reveals ancient synteny. J Immunol 164:5296–5305Google Scholar
  109. Miller KM, Withler RE (1998) The salmonid class I MHC: limited diversity in a primitive teleost. Immunol Rev 166:279–293Google Scholar
  110. Miller MM, Goto RM, Bernot A, Zoorob R, Auffray C, Bumstead N, Briles WE (1994) Two MHC class I and two MHC class II genes map to the chicken Rfp-Y system outside the B complex. Proc Natl Acad Sci USA 91:4397–4401PubMedGoogle Scholar
  111. Milner CM, Campbell RD (2001) Genetic organization of the human MHC class III region. Front Biosci 6:D914–D926PubMedGoogle Scholar
  112. Miska K, Miller RD (1999) Marsupial MHC class I: classical sequences from the opossum, Monodelphis domestica. Immunogenetics 50:89–93Google Scholar
  113. Miska K, Harrison GA, Hellman L, Miller RD (2002) The major histocompatibility complex in monotremes: an analysis of the evolution of MHC class I genes across all three mammalian subclasses. Immunogenetics 54:381–393Google Scholar
  114. Monaco JJ (1992) Major histocompatibility complex-linked transport proteins and antigen processing. Immunol Res 11:125–132PubMedGoogle Scholar
  115. Moretta A, Vitale M, Bottino C, Orengo AM, Morelli L, Augugliaro R, Barbaresi M, Ciccone E, Moretta L (1993) p58 Molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I protected cells in NK clones displaying different specificities. J Exp Med 178:597–604CrossRefPubMedGoogle Scholar
  116. Müller WE, Blumbach B, Müller IM (1999) Evolution of the innate and adaptive immune systems: relationships between potential immune molecules in the lowest metazoan phylum (Porifera) and those in vertebrates. Transplantation 68:1215–1227PubMedGoogle Scholar
  117. Müller WE, Krasko A, Skorokhod A, Bünz C, Grebenjuk VA, Steffen R, Batel R, Schröder HC (2002) Histocompatibility reaction in tissue and cells of the marine sponge Suberites domuncula in vitro and in vivo: central role of the allograft inflammatory factor 1. Immunogenetics 54:48–58Google Scholar
  118. Murray BW, Sültmann H, Klein J (1999) Analysis of a 26-kb region linked to the MHC in zebrafish: genomic organization of the proteasome component beta/transporter associated with antigen processing-2 gene cluster and identification of five new proteasome beta subunit genes. J Immunol 163:2657–2666Google Scholar
  119. Murray BW, Nilsson P, Zaleska-Rutczynska Z, Sultmann H, Klein J (2000) Linkage relationships and haplotype variation of the major histocompatibility complex class I A genes in the cichlid fish Oreochromis niloticus. Mar Biotechnol (NY) 2:437–448Google Scholar
  120. Naper C, Ryan JC, Kirsch R, Butcher GW, Rolstad B, Vaage JT (1999) Genes in two major histocompatibility complex class I regions control selection, phenotype, and function of a rat Ly-49 natural killer cell subset. Eur J Immunol 29:2046–2053Google Scholar
  121. Nizetic D, Figueroa F, Dembic Z, Nevo E, Klein J (1987) Major histocompatibility complex gene organization in the mole rat Spalax ehrenbergi: evidence for transfer of function between class II genes. Proc Natl Acad Sci USA 84:5828–5832Google Scholar
  122. Nonaka M (2001) Evolution of the complement system. Curr Opin Immunol 13:69–73Google Scholar
  123. Nonaka M, Namikawa C, Kato Y, Sasaki M, Salter-Cid L, Flajnik MF (1997) Major histocompatibility complex gene mapping in the amphibian Xenopus implies a primordial organization. Proc Natl Acad Sci USA 94:5789–5791Google Scholar
  124. Nonaka M, Matsuo M, Naruse K, Shima A (2001) Comparative genomics of medaka: the major histocompatibility complex (MHC). Mar Biotechnol (NY) 3:141–144Google Scholar
  125. O’Callaghan CA, Bell JI (1998) Structure and function of the human MHC class Ib molecules HLA-E, HLA-F, and HLA-G. Immunol Rev 163:129–138Google Scholar
  126. Ohta Y, Kazuhiko O, McKinney EC, Bartl S, Hashimoto K, Flajnik MF (2000) Primitive synteny of vertebrate major histocompatibility complex class I and class II genes. Proc Natl Acad Sci USA 97:4712–4717Google Scholar
  127. Ohta Y, McKinney EC, Criscitiello MF, Flajnik MF (2002) Proteasome, transporter associated with antigen processing, and class I genes in the nurse shark Ginglymostoma cirratum: evidence for a stable class I region and MHC haplotype lineages. J Immunol 168:771–781Google Scholar
  128. Ohta Y, Powis SH, Lohr RL, Nonaka M, Pasquier LD, Flajnik MF (2003) Two highly divergent ancient allelic lineages of the transporter associated with antigen processing (TAP) gene in Xenopus: further evidence for co-evolution among MHC class I region genes. Eur J Immunol 33:3017–3027Google Scholar
  129. Okamura K, Ototake M, Nakanishi T, Kurosawa Y, Hashimoto K (1997) The most primitive vertebrates with jaws possess highly polymorphic MHC class I genes comparable to those of humans. Immunity 7:777–790CrossRefPubMedGoogle Scholar
  130. Pancer Z, Amemiya CT, Ehrhardt GRA, Ceitlin J, Gartland GL, Cooper MD (2004) Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey. Nature 430:174–180CrossRefPubMedGoogle Scholar
  131. Persson A-C, Stet RJM, Pilstrom L (1999) Characterization of MHC class I and beta(2)-microglobulin sequences in Atlantic cod reveals an unusually high number of expressed class I genes. Immunogenetics 50:49–59Google Scholar
  132. van der Poel JJ, Groenen MA, Dijkhof RJ, Ruyter D, Giphart MJ (1990) The nucleotide sequence of the bovine MHC class II alpha genes: DRA, DOA, and DYA. Immunogenetics 31:29–36Google Scholar
  133. Radtkey RR, Becker B, Miller RD, Riblet R, Case TJ (1996) Variation and evolution of class I MHC in sexual and parthenogenetic geckos. Proc R Soc Lond B Biol Sci 263:1023–1032PubMedGoogle Scholar
  134. Ritz U, Seliger B (2001) The transporter associated with antigen processing (TAP): structural integrity, expression, function, and its clinical relevance. Mol Med 7:149–158PubMedGoogle Scholar
  135. Rolstad B, Naper C, Lovik G, Vaage JT, Ryan JC, Backman-Petersson E, Kirsch RD, Butcher GW (2002) Rat natural killer cell receptor systems and recognition of MHC class I molecules. Immunol Rev 181:149–157Google Scholar
  136. Sadasivan B, Lehner PJ, Ortmann B, Spies T, Cresswell P (1996) Roles of calreticulin and a novel glycoprotein, tapasin, in the interaction of MHC class I molecules with TAP. Immunity 5:103–114CrossRefPubMedGoogle Scholar
  137. Salomonsen J, Marston D, Avila D, Bumstead N, Johansson B, Juul-Madsen H, Olesen GD, Riegert P, Skjodt K, Vainio O, Wiles MV, Kaufman J (2003) The properties of the single chicken MHC class II alpha chain (B-LA) gene indicate an ancient origin for the DR/E-like isotype of class II molecules. Immunogenetics 55:605–614CrossRefPubMedGoogle Scholar
  138. Sambrook JG, Russell R, Umrania Y, Edwards YJ, Campbell RD, Elgar G, Clark MS (2002) Fugu orthologues of human major histocompatibility complex genes: a genome survey. Immunogenetics 54:367–380CrossRefPubMedGoogle Scholar
  139. Sambrook JG, Campbell RD, Elgar G (2003) Characterisation of a gene cluster in Fugu rubripes containing the complement component C4 gene. Gene 312:73–83CrossRefPubMedGoogle Scholar
  140. Sammut B, Du Pasquier L, Ducoroy P, Laurens V, Marcuz A, Tournefier A (1999) Axolotl MHC architecture and polymorphism. Eur J Immunol 29:2897–2907Google Scholar
  141. Sammut B, Marcuz A, Du Pasquier L (2002) The fate of duplicated major histocompatibility complex class Ia Genes in a dodecaploid amphibian, Xenopus ruwenzoriensis. Eur J Immunol 32:2698–2709Google Scholar
  142. Sato K, Flajnik MF, Du Pasquier L, Katagiri M, Kasahara M (1993) Evolution of the MHC: isolation of class II beta-chain cDNA clones from the amphibian Xenopus laevis. J Immunol 150:2831–2843Google Scholar
  143. Sato A, Figueroa F, Murray BW, Malaga-Trillo E, Zaleska-Rutczynska Z, Sultmann H, Toyosawa S, Wedekind C, Steck N, Klein J (2000) Nonlinkage of major histocompatibility complex class I and class II loci in bony fishes. Immunogenetics 51:108–116CrossRefPubMedGoogle Scholar
  144. Scott PC, Choi CL, Brandon MR (1987) Genetic organization of the ovine MHC class II region. Immunogenetics 25:116–122Google Scholar
  145. Seo JW, Bontrop RE, Walter L, Günther E (1999) Major histocompatibility complex-linked MIC genes in rhesus macaques and other primates. Immunogenetics 50:358–362Google Scholar
  146. Seo JW, Walter L, Günther E (2001) Genomic analysis of MIC genes in rhesus macaques. Tissue Antigens 58:159–165CrossRefPubMedGoogle Scholar
  147. Shiina T, Shimizu C, Oka A, Teraoka Y, Imanishi T, Gojobori T, Hanzawa K, Watanabe S, Inoko H (1999a) Gene organization of the quail major histocompatibility complex (MhcCoja) class I gene region. Immunogenetics 49:384–394CrossRefPubMedGoogle Scholar
  148. Shiina T, Tamiya G, Oka A, Takishima N, Yamagata T, Kikkawa E, Iwata K, Tomizawa M, Okuaki N, Kuwano Y, Wantanabe K, Fukuzumi Y, Itakura S, Sugawara C, Ono A, Yamazaki M, Tashiro H, Ando A, Ikemura T, Soeda E, Kimura M, Bahram S, Inoko H (1999b) Molecular dynamics of MHC genesis unraveled by sequence analysis of the 1,796,938-bp HLA class I region. Proc Natl Acad Sci USA 96:13282–13287Google Scholar
  149. Shiina T, Shimizu S, Hosomichi K, Kohara S, Watanabe S, Hanzawa K, Beck S, Kulski JK, Inoko H (2004) Comparative genomic analysis of two avian (Quail and Chicken) MHC regions. J Immunol 172:6751–6763PubMedGoogle Scholar
  150. Shum BP, Avila D, Du Pasquier L, Kasahara M, Flajnik MF (1993) Isolation of a classical class I cDNA from an amphibian. Evidence for only one class I locus in the Xenopus MHC. J Immunol 151:5376–5386Google Scholar
  151. Shum BP, Guethlein L, Flodin LR, Adkison MA, Hedrick RP, Nehring RB, Stet RJM, Secombes C, Parham P (2001) Modes of salmonid MHC class I and II evolution differ from the primate paradigm. J Immunol 166:3297–3308PubMedGoogle Scholar
  152. Sidebottom DA, Kennedy R, Hildebrand WH (2001) Class I MHC expression in the yellow baboon. J Immunol 166:3983–3993Google Scholar
  153. Singer DS, Mozes E, Kirshner S, Kohn LD (1997) Role of MHC class I molecules in autoimmune disease. Crit Rev Immunol 17:463–468PubMedGoogle Scholar
  154. Snell GD (1981) Studies in histocompatibility. Science 213:172–178Google Scholar
  155. Springer MS, Murphy WJ, Eizirik E, O’Brien SJ (2003) Placental mammal diversification and the cretaceous-tertiary boundary. Proc Natl Acad Sci USA 100:1056–1061CrossRefPubMedGoogle Scholar
  156. Steffer A, Schubart A, Storch M, Amini A, Mather I, Lassmann H, Linington C (2000) Butyrophilin, a milk protein, modulates the encephalitogenic T cell response to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis. J Immunol 165:2859–2865Google Scholar
  157. Stenzel A, Lu T, Koch WA, Hampe J, Guenther SM, De La Vega FM, Krawczak M, Schreiber S (2004) Patterns of linkage disequilibrium in the MHC region on human chromosome 6p. Hum Genet 114:377–385CrossRefPubMedGoogle Scholar
  158. Stephens R, Horton R, Humphray S, Rowen L, Trowsdale J, Beck S (1999) Gene organisation, sequence variation and isochore structure at the centromeric boundary of the human MHC. J Mol Biol 291:789–799CrossRefPubMedGoogle Scholar
  159. Stet RJM, Johnstone R, Parham P, Wiegertjes GF (1997) The unMHC of teleostean fish: segregation analyses in common carp and Atlantic salmon. Hereditas 127:169–170Google Scholar
  160. Stet RJM, Kruiswijk CP, Saeij JP, Wiegertjes GF (1998) Major histocompatibility genes in cyprinid fishes: theory and practice. Immunol Rev 166:301–316Google Scholar
  161. Stone RT, Muggli-Cockett NE (1990) Partial nucleotide sequence of a novel bovine major histocompatibility complex class II beta-chain gene, BoLA-DIB. Anim Genet 21:353–360PubMedGoogle Scholar
  162. Sudbrak R, Reinhardt R, Hennig S, Lehrach H, Günther E, Walter L (2003) Comparative and evolutionary analysis of the rhesus macaque extended MHC class II region. Immunogenetics 54:699–704Google Scholar
  163. Sültmann H, Murray BW, Klein J (2000) Identification of seven genes in the major histocompatibility complex class I region in zebrafish. Scand J Immunol 51:577–585Google Scholar
  164. Takada T, Kumanovics A, Amadou C, Yoshino M, Jones EP, Athanasiou M, Evans GA, Lindahl KF (2003) Species-specific class I gene expansions formed the telomeric 1 Mb of the mouse major histocompatibility complex. Genome Res 13:589–600CrossRefPubMedGoogle Scholar
  165. Takahashi K, Rooney AP, Nei M (2000) Origins and divergence times of mammalian class II MHC gene clusters. J Hered 91:198–204CrossRefPubMedGoogle Scholar
  166. Takami K, Zaleska-Rutczynska Z, Figueroa F, Klein J (1997) Linkage of LMP, TAP, and RING3 with MHC class I rather than class II genes in the zebrafish. J Immunol 159:6052–6060Google Scholar
  167. Terado T, Okamura K, Ohta Y, Shin D-H, Smith SL, Hashimoto K, Takemoto T, Nonaka MI, Kimura H, Flajnik MF, Nonaka M (2003) Molecular cloning of C4 gene and identification of the class III complement region in the shark MHC. J Immunol 171:2461–2466Google Scholar
  168. Totaro A, Rommens JM, Grifa A, Lunardi C, Carella M, Huizenga JJ, Roetto A, Camaschella C, De Sandre G, Gasparini P (1996) Hereditary hemochromatosis: generation of a transcription map within a refined and extended map of the HLA class I region. Genomics 31:319–326CrossRefPubMedGoogle Scholar
  169. Trachtulec Z, Hamvas RM, Forejt J, Lehrach H, Vincek V, Klein J (1997) Linkage of TATA-binding protein and proteasome subunit C5 genes in mice and humans reveals synteny conserved between mammals and invertebrates. Genomics 44:1–7CrossRefPubMedGoogle Scholar
  170. Trowsdale J (1995) “Both Man & Bird & Beast”: comparative organization of MHC genes. Immunogenetics 41:1–17Google Scholar
  171. Trowsdale J (2001) Genetic and functional relationships between MHC and NK receptor genes. Immunity 15:363–374CrossRefPubMedGoogle Scholar
  172. Trowsdale J (2002) The gentle art of gene arrangement: the meaning of gene clusters. Genome Biol 3:2002.1–2002.5CrossRefGoogle Scholar
  173. Trowsdale J, Parham P (2004) Defense strategies and immune-related genes. Eur J Immunol 34:7–17Google Scholar
  174. Tsuda TT, Tsuda M, Naruse T, Kawata H, Ando A, Shiina T, Fukuda M, Kurita M, LeMaho I, Kulski JK, Inoko H (2001) Phylogenetic analysis of penguin (Spheniscidae) species based on sequence variation in MHC class II genes. Immunogenetics 53:712–716CrossRefPubMedGoogle Scholar
  175. Villadangos JA (2001) Presentation of antigens by MHC class II molecules: getting the most out of them. Mol Immunol 38:329–346Google Scholar
  176. Vogel TU, Evans DT, Urvater JA, O’Connor DH, Hughes AL, Watkins DI (1999) Major histocompatibility complex class I genes in primates: co-evolution with pathogens. Immunol Rev 167:327–337Google Scholar
  177. Wagner JL (2003) Molecular organization of the canine major histocompatibility complex. J Hered 94:23–26CrossRefPubMedGoogle Scholar
  178. Walter L, Günther E (2000) Physical mapping and evolution of the centromeric class I gene-containing region of the rat MHC. Immunogenetics 51:829–837CrossRefPubMedGoogle Scholar
  179. Walter L, Hurt P, Himmelbauer H, Sudbrak R, Günther E (2002) Physical mapping of the major histocompatibility complex class II and class III regions of the rat. Immunogenetics 54:268–275CrossRefPubMedGoogle Scholar
  180. Wang C, Perera TV, Ford HL, Dascher CC (2003) Characterization of a divergent non-classical MHC class I gene in sharks. Immunogenetics 55:57–61Google Scholar
  181. Watanabe Y, Maruoka T, Walter L, Kasahara M (2004) Comparative genomics of the mill family: a rapidly evolving MHC class I gene family. Eur J Immunol 34:1597–1607Google Scholar
  182. Watkins DI (1995) The evolution of major histocompatibility class I genes in primates. Crit Rev Immunol 15:1–29PubMedGoogle Scholar
  183. Westerdahl H, Wittzell H, von Schantz T (1999) Polymorphism and transcription of MHC class I genes in a passerine bird, the great reed warbler. Immunogenetics 49:158–170CrossRefPubMedGoogle Scholar
  184. Westerdahl H, Wittzell H, von Schantz T (2000) MHC diversity in two passerine birds: no evidence for a minimal essential MHC. Immunogenetics 52:92–100CrossRefPubMedGoogle Scholar
  185. Wiegertjes GF, Egberts E, Stet RJM (1997) Segregation of MHC class I and class II genes in the common carp (Cyprinus carpio L.). Dev Comp Immunol 21:105CrossRefGoogle Scholar
  186. Williams A, Peh CA, Elliott T (2002) The cell biology of MHC class I antigen presentation. Tissue Antigens 59:3–17CrossRefPubMedGoogle Scholar
  187. Wittzell H, Madsen T, Westerdahl H, Shine R, von Schantz T (1998–1999) MHC variation in birds and reptiles. Genetica 104:301–309CrossRefGoogle Scholar
  188. Wright H, Ballingall KT, Redmond J (1994) The DY sub-region of the sheep MHC contains and A/B gene pair. Immunogenetics 40:230–234Google Scholar
  189. Xie T, Rowen L, Aguado B, Ahearn ME, Madan A, Qin S, Campbell RD, Hood L (2003) Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse. Genome Res 13:2621–2636CrossRefPubMedGoogle Scholar
  190. Yeager M, Kumar S, Hughes AL (1997) Sequence convergence in the peptide-binding region of primate and rodent MHC class Ib molecules. Mol Biol Evol 14:1035–1041PubMedGoogle Scholar
  191. Yuhki N, Beck T, Stephens RM, Nishigaki Y, Newmann K, O’Brien SJ (2003) Comparative genome organization of human, murine, and feline MHC class II region. Genome Res 13:1169–1179CrossRefPubMedGoogle Scholar
  192. Zekarias B, Ter Huurne AAHM, Landman WJM, Rebel JMJ, Pol JMA, Gruys E (2002) Immunological basis of differences in disease resistance in chicken. Vet Res 33:109–125CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Immunology Division, Department of PathologyUniversity of CambridgeCambridgeUK
  2. 2.Department of Primate GeneticsGerman Primate CenterGöttingenGermany

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