Medaka pp 351-364 | Cite as

Evolution of the Major Histocompatibility Complex: A Lesson from the Oryzias Species

  • Masaru Nonaka
  • Kentaro Tsukamoto


The genomic organization of the teleost major histocompatibility complex (MHC) shows a significant deviation from that of the “standard” MHC of the eutherian mammals in that the class IA genes are not linked to the class IIA and B genes. However, progress in the phylogenetic analysis of the jawed vertebrate MHC reveals that the “standard” mammalian MHC is also highly derived because the tight linkage between the class IA genes and the genes directly involved in the class I antigen processing/presentation process is disrupted. In the medaka MHC class I region, these genes form a tight and uninterrupted cluster, probably reflecting the ancestral genomic organization of the MHC. One of these genes, PSMB8 (proteasome subunit beta type 8), which is responsible for the generation of the peptides presented by the MHC class I molecules, shows a marked dimorphism in medaka. The same dimorphic alleles are present in other Oryzias species, indicating that they are under balancing selection and have been transmitted from species to species. Although the physiological or evolutionary meaning of this balancing selection is still to be clarified, similar dimorphisms of PSMB8 are widely recognized among non-eutherian vertebrates, suggesting that the presence of the PSMB8 dimorphism is associated with the tight linkage between the class IA genes and the genes directly involved in the class I antigen processing/presentation process.


Major Histocompatibility Complex Major Histocompatibility Complex Class Bacterial Artificial Chromosome Clone Major Histocompatibility Complex Region Human Major Histocompatibility Complex 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Belov K, Deakin JE, Papenfuss AT, Baker ML, Melman SD, Siddle HV, Gouin N, Goode DL, Sargeant TJ, Robinson MD, Wakefield MJ, Mahony S, Cross JG, Benos PV, Samollow PB, Speed TP, Graves JA, Miller RD (2006) Reconstructing an ancestral mammalian immune supercomplex from a marsupial major histocompatibility complex. PLoS Biol 4:e46PubMedCrossRefGoogle Scholar
  2. 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 46:129–134PubMedCrossRefGoogle Scholar
  3. 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 52:174–185PubMedCrossRefGoogle Scholar
  4. Consortium TM (1999) Complete sequence and gene map of a human major histocompatibility complex. The MHC sequencing consortium. Nature (Lond) 401:921–923CrossRefGoogle Scholar
  5. Dohm JC, Tsend-Ayush E, Reinhardt R, Grutzner F, Himmelbauer H (2007) Disruption and pseudoautosomal localization of the major histocompatibility complex in monotremes. Genome Biol 8:R175PubMedCrossRefGoogle Scholar
  6. Flajnik MF, Kasahara M (2001) Comparative genomics of the MHC: glimpses into the evolution of the adaptive immune system. Immunity 15:351–362PubMedCrossRefGoogle Scholar
  7. Groll M, Ditzel L, Lowe J, Stock D, Bochtler M, Bartunik HD, Huber R (1997) Structure of 20S proteasome from yeast at 2.4  Å resolution. Nature (Lond) 386:463–471CrossRefGoogle Scholar
  8. Hedrick PW (2006) Genetic polymorphism in heterogeneous environments: the age of genomics. Annu Rev Ecol Evol Syst 37:67–93CrossRefGoogle Scholar
  9. Joly E, Le Rolle AF, 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 8:169–172PubMedCrossRefGoogle Scholar
  10. Kasahara M, Naruse K, Sasaki S, Nakatani Y, Qu W, Ahsan B, Yamada T, Nagayasu Y, Doi K, Kasai Y, Jindo T, Kobayashi D, Shimada A, Toyoda A, Kuroki Y, Fujiyama A, Sasaki T, Shimizu A, Asakawa S, Shimizu N, Hashimoto S, Yang J, Lee Y, Matsushima K, Sugano S, Sakaizumi M, Narita T, Ohishi K, Haga S, Ohta F, Nomoto H, Nogata K, Morishita T, Endo T, Shin IT, Takeda H, Morishita S, Kohara Y (2007) The medaka draft genome and insights into vertebrate genome evolution. Nature (Lond) 447:714–719CrossRefGoogle Scholar
  11. Kaufman J, Milne S, Gobel TW, Walker BA, Jacob JP, Auffray C, Zoorob R, Beck S (1999) The chicken B locus is a minimal essential major histocompatibility complex. Nature (Lond) 401:923–925CrossRefGoogle Scholar
  12. Kelley J, Walter L, Trowsdale J (2005) Comparative genomics of major histocompatibility complexes. Immunogenetics 56:683–695PubMedCrossRefGoogle Scholar
  13. Klein J, Satta Y, O’Huigin C, Takahata N (1993) The molecular descent of the major histocompatibility complex. Annu Rev Immunol 11:269–295PubMedCrossRefGoogle Scholar
  14. Lukacs MF, Harstad H, Grimholt U, Beetz-Sargent M, Cooper GA, Reid L, Bakke HG, Phillips RB, Miller KM, Davidson WS, Koop BF (2007) Genomic organization of duplicated major histocompatibility complex class I regions in Atlantic salmon (Salmo salar). BMC Genomics 8:251PubMedCrossRefGoogle Scholar
  15. 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 53:930–940PubMedCrossRefGoogle Scholar
  16. Mehta RB, Nonaka MI, Nonaka M (2009) Comparative genomic analysis of the major histocompatibility complex class I region in the teleost genus Oryzias. Immunogenetics 61:385–399PubMedCrossRefGoogle Scholar
  17. 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 164:5296–5305PubMedGoogle Scholar
  18. Murata S, Sasaki K, Kishimoto T, Niwa S, Hayashi H, Takahama Y, Tanaka K (2007) Regulation of CD8+ T cell development by thymus-specific proteasomes. Science 316:1349–1353PubMedCrossRefGoogle Scholar
  19. Naruse K, Fukamachi S, Mitani H, Kondo M, Matsuoka T, Kondo S, Hanamura N, Morita Y, Hasegawa K, Nishigaki R, Shimada A, Wada H, Kusakabe T, Suzuki N, Kinoshita M, Kanamori A, Terado T, Kimura H, Nonaka M, Shima A (2000) A detailed linkage map of medaka, Oryzias latipes: comparative genomics and genome evolution. Genetics 154:1773–1784PubMedGoogle Scholar
  20. Ohta Y, Okamura K, 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 97:4712–4717PubMedCrossRefGoogle Scholar
  21. Ohta Y, Powis SJ, 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 33:3017–3027PubMedCrossRefGoogle Scholar
  22. Ohta Y, Goetz W, Hossain MZ, Nonaka M, Flajnik MF (2006) Ancestral organization of the MHC revealed in the amphibian Xenopus. J Immunol 176:3674–3685PubMedGoogle Scholar
  23. Rammensee HG, Friede T, Stevanoviic S (1995) MHC ligands and peptide motifs: first listing. Immunogenetics 41:178–228PubMedCrossRefGoogle Scholar
  24. Rock KL, Goldberg AL (1999) Degradation of cell proteins and the generation of MHC class I-presented peptides. Annu Rev Immunol 17:739–779PubMedCrossRefGoogle Scholar
  25. Rock KL, York IA, Goldberg AL (2004) Post-proteasomal antigen processing for major histocompatibility complex class I presentation. Nat Immunol 5:670–677PubMedCrossRefGoogle Scholar
  26. 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
  27. Shiina T, Dijkstra JM, Shimizu S, Watanabe A, Yanagiya K, Kiryu I, Fujiwara A, Nishida-Umehara C, Kaba Y, Hirono I, Yoshiura Y, Aoki T, Inoko H, Kulski JK, Ototake M (2005) Interchromosomal duplication of major histocompatibility complex class I regions in rainbow trout (Oncorhynchus mykiss), a species with a presumably recent tetraploid ancestry. Immunogenetics 56:878–893PubMedCrossRefGoogle Scholar
  28. Takehana Y, Nagai N, Matsuda M, Tsuchiya K, Sakaizumi M (2003) Geographic variation and diversity of the cytochrome b gene in Japanese wild populations of medaka, Oryzias latipes. Zool Sci 20:1279–1291PubMedCrossRefGoogle Scholar
  29. Takehana Y, Naruse K, Sakaizumi M (2005) Molecular phylogeny of the medaka fishes genus Oryzias (Beloniformes: Adrianichthyidae) based on nuclear and mitochondrial DNA sequences. Mol Phylogenet Evol 36:417–428PubMedCrossRefGoogle Scholar
  30. Tanaka K, Kasahara M (1998) The MHC class I ligand-generating system: roles of immuno­proteasomes and the interferon-gamma-inducible proteasome activator PA28. Immunol Rev 163:161–176PubMedCrossRefGoogle Scholar
  31. Tsukamoto K, Hayashi S, Matsuo MY, Nonaka MI, Kondo M, Shima A, Asakawa S, Shimizu N, Nonaka M (2005) Unprecedented intraspecific diversity of the MHC class I region of a teleost medaka, Oryzias latipes. Immunogenetics 57:420–431PubMedCrossRefGoogle Scholar
  32. Tsukamoto K, Sakaizumi M, Hata M, Sawara Y, Eah J, Kim CB, Nonaka M (2009) Dichotomous haplotypic lineages of the immunoproteasome subunit genes, PSMB8 and PSMB10, in the MHC class I region of a teleost medaka, Oryzias latipes. Mol Biol Evol 26:769–781PubMedCrossRefGoogle Scholar
  33. Unno M, Mizushima T, Morimoto Y, Tomisugi Y, Tanaka K, Yasuoka N, Tsukihara T (2002) The structure of the mammalian 20S proteasome at 2.75  Ǻ resolution. Structure 10:609–618PubMedCrossRefGoogle Scholar
  34. Zinkernagel RM, Doherty PC (1979) MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol 27:51–177PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  1. 1.Department of Biological Sciences, Graduate School of ScienceThe University of TokyoBunkyo-kuJapan
  2. 2.Institute for Comprehensive Medical ScienceFujita Health UniversityShinjuku-kuJapan

Personalised recommendations