The genomic sequences within the alpha-block (∼288–310 kb) of the human and chimpanzee MHC class I region contains ten MHC class I genes and three MIC gene fragments grouped together within alternating duplicated genomic segments or duplicons. In this study, the chimpanzee and human genomic sequences were analyzed in order to determine whether the remnants of the ERVK9 and other retrotransposon sequences are useful genomic markers for reconstructing the evolutionary history of the duplicated MHC gene families within the alpha-block. A variety of genes, pseudogenes, autologous DNA transposons and retrotransposons such as Alu and ERVK9 were used to categorize the ten duplicons into four distinct structural groups. The phylogenetic relationship of the ten duplicons was examined by using the neighbour joining method to analyze transposon sequence topologies of selected Alu members, LTR16B and Charlie9. On the basis of these structural groups and the phylogeny of the duplicated transposon sequences, a duplication model was reconstructed involving four multipartite tandem duplication steps to explain the organization and evolution of the ten duplicons within the alpha-block of the chimpanzee and human. The phylogenetic analysis and inferred duplication history suggests that the Patr/HLA-F was the first MHC class I gene to have been fixed and not required as a precursor for further duplication within the alpha-block of the ancestral species.   

1.
Aida K, Russomando G, Kikuchi M, Candia N et al: High frequency of MIC null haplotype (HLA-B48-MICA-del-MICB*0107 N) in the Angaite Amerindian community in Paraguay. Immunogenetics 54:439–444 (2002).
2.
Amadou C: Evolution of the MHC class I region: the framework hypothesis. Immunogenetics 49:362–367 (1999).
3.
Anzai T, Shiina T, Kimura T, 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: 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 100:7708–7713 (2003).
4.
Avoustin P, Ribouchon MT, Vernet C, N’Guyen B, Crouau-Roy B, Pontarotti P: Non-homologous recombination within the major histocompatibility complex creates a transcribed hybrid sequence. Mamm Genome 5:771–776 (1994).
5.
Bahram S, Bresnahan M, Geraghty DE, Spies T: A second lineage of mammalian major histocompatibility complex class I genes. Proc Natl Acad Sci USA 91:6259–6263 (1994).
6.
Chen EY, Liao YC, Smith DH, Barrera-Saldana H, Gelinas RE, Seeburg PH: The human growth hormone locus: nucleotide sequence, biology, and evolution. Genomics 4:479–497 (1989).
7.
Dangel AW, Baker BJ, Mendoza AR, Yu CY: Complement component C4 gene intron 9 as a phylogenetic marker for primates: long terminal repeats of the endogenous retrovirus ERV-K(C4) are a molecular clock of evolution. Immunogenetics 42:41–52 (1995).
8.
Dawkins RL, Leelayuwat C, Gaudieri S, Tay G, Cattley S, Martinez P, Kulski JK: Genomics of the Major Histocompatibility Complex: Haplotypes, retroviruses and disease. Immun Rev 167:275–304 (1999).
9.
El Kahloun A, Chauvel B, Mauvieux V, Dorval I, Jouanolle A-M, Gicquel I, Le Gall J-Y, David V: Localization of seven new genes around the HLA-A locus. Hum Mol Genet 2:55–60 (1993).
10.
Freitis EM, Gaudieri S, Zhang WJ, Kulski JK, van Bockxmeer FM, Christiansen, FT, Dawkins RL: The role of retroelements in the duplication and diversification of apolipoprotein CI (Apo CI). J Mol Evol 50:391–396 (2000).
11.
Gaudieri S, Giles K, Kulski J, Dawkins R: Duplication and polymorphism in the MHC: Alu generated diversity and polymorphism within the PERB11 gene family. Hereditas 127:37–46 (1997).
12.
Gaudieri S, Kulski JK, Dawkins RL, Gojobori T: Different evolutionary histories in two subgenomic regions of the Major Histocompatibility Complex. Genome Res 9:541–549 (1999a).
13.
Gaudieri S, Kulski JK, Dawkins RL, Gojobori T: Extensive nucleotide variability within a 370 kb sequence from the central region of the Major Histocompatibility Complex. Gene 238:157–161 (1999b).
14.
Gaudieri S, Habara K, Kulski JK, Dawkins RL, Gojobori T: SNP profile within the Human Histocompatibility Complex reveals an extreme and interrupted level of nucleotide diversity. Genome Res 10:1579–1586 (2000).
15.
Geraghty DE, Koller BH, Hansen JA, Orr HT: The HLA class I gene family includes at least six genes and twelve pseudogenes and gene fragments. J Immunol 149:1934–1946 (1992).
16.
Hampe A, Coriton O, Andrieux N, Carn G, Lepourcelet M, Mottier S, Dreano S, Gatius MT, Hitte C, Soriano N, Galibert F: A 356-Kb sequence of the subtelomeric part of the MHC Class I Region. DNA Seq 10:263–299 (1999).
17.
Hughes AL: Origin and evolution of HLA class I pseudogenes. Mol Biol Evol 12:247–258 (1995).
18.
Hughes JF, Coffin JM: Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution. Nat Genet 29:487–489 (2001).
19.
Jurka J: Interspersed element MER112. RepBase Update 6.8 (1999).
20.
Jurka J, Kapitonov VV, Klonowski P, Walichiewicz J, Smit AFA: Identification of new medium reiteration frequency repeats in the genomes of Primates, Rodentia and Lagomorpha. Genetica 98:235–247 (1996a).
21.
Jurka J, Klonowski P, Dagman V, Pelton P: CENSOR- a program for identification and elimination of repetitive elements from DNA sequences. Comp Chem 20:119–121 (1996b).
22.
Klein J, Sato A, O’hUigin C: Evolution by gene duplication in the major histocompatibility complex. Cytogenet Cell Genet 80:123–127 (1998).
23.
Komatsu-Wakui M, Tokunaga K, Ishikawa Y, et al: MIC-A polymorphism in Japanese and a MIC-A-MIC-B null haplotype. Immunogenetics 49:620–628 (1999).
24.
Komatsu-Wakui M, Tokunaga K, Ishikawa Y, Leelayuwat C, Kashiwase K, Tanaka H, Moriyama S, Nakajima F, Park MH, Jia GJ, Chimge NO, Sideltseva EW, Juji T: Wide distribution of the MICA-MICB null haplotype in East Asians. Tissue Antigens 57:1–8 (2001).
25.
Kulski JK, Dawkins RL: The P5 multicopy gene family in the MHC is related in sequence to human endogenous retroviruses HERV-L and HERV-16. Immunogenetics 49:404–412 (1999).
26.
Kulski JK, Gaudieri S, Bellgard M, Balmer L, Giles K, Inoko H, Dawkins RL: The evolution of MHC diversity by segmental duplication and transposition of retroelements. J Mol Evol 45:599–609 (1997).
27.
Kulski JK, Gaudieri S, Inoko H, Dawkins RL: Comparison between two HERV-rich regions within the major histocompatibility complex. J Mol Evol 48: 675–683 (1999a).
28.
Kulski JK, Gaudieri S, Martin A, Dawkins RL: Co-evolution of PERB11 (MIC) and HLA class I genes with HERV-16 and retroelements by extended genomic duplication. J Mol Evol 49:84–97 (1999b).
29.
Kulski, JK, Gaudieri S, Dawkins RL: Transposable elements and the metamerismatic evolution of the HLA class I region, in Kasahara, M (ed): The Major Histocompatibility Complex: Evolution, Structure, and Function, pp 158–177 (Springer-Verlag, Berlin 2000a).
30.
Kulski JK, Gaudieri S, Dawkins RL: Using Alu J elements as molecular clocks to trace the evolutionary relationships between duplicated HLA class I segments. J Mol Evol 50:510–519 (2000b).
31.
Kulski JK, Dunn DS, Gaudieri S, Shiina T, Inoko H: Genomic and phylogenetic analysis of the human CD1 and HLA class I multicopy genes. J Mol Evol 53:642–650 (2001).
32.
Kulski JK, Shiina T, Anzai T, Kohara S, Inoko H: Comparative genomic analysis of the MHC: the evolution of class I duplication blocks, diversity and complexity from shark to man. Immunol Rev 190:95–122 (2002).
33.
Kulski JK, Lim CP, Dunn DS, Bellgard M: Genomic and phylogenetic analysis of the S100A7 (Psoriasin) gene duplications within the region of the S100 gene cluster on human chromosome 1q21. J Mol Evol 56:397–406 (2003).
34.
Kumar S, Tamura K, Nei M: MEGA: Molecular evolutionary genetic analysis (Pennsylvania State University, University Park 1993).
35.
Leelayuwat C, Townsend DC, Degli-Esposti MA, Abraham LJ, Dawkins RL: A new polymorphic and multicopy MHC gene family related to non-mammalian class I. Immunogenetics 40:339–351 (1994).
36.
Leelayuwat C, Pinelli M, Dawkins RL: Clustering of diverse replicated sequences in the MHC. Evidence for en bloc duplication. J Immunol 155:692–698 (1995).
37.
Liao D, Pavelitz T, Weiner AM: Characterization of a novel class of interspersed LTR elements in primate genomes: structure, genome distribution, and evolution. J Mol Evol 46:649–660 (1998).
38.
Martin AM, Freitas EM, Witt C, Christiansen F: The genomic organisation and evolution of the natural killer immunoglobulin-like receptor (KIR) gene cluster. Immunogenetics 51:268–280 (2000).
39.
Mizuki N, Ando H, Kimura M, Ohno S, Miyata S, Yamazaki M, Tashiro H, Watanabe K, Ono A, Taguchi S, Sugawara C, Fukuzumi Y, Okumura K, Goto K, Ishihara M, Nakamura S, Yonemoto J, Kikuti YY, Shiina T, Chen L, et al: Nucleotide sequence analysis of the HLA class I region spanning the 237-kb segment around the HLA-B and -C genes. Genomics 42:55–66 (1997).
40.
Mnukova-Fajdelova M, Satta Y, O’hUigin C, Mayer WE, Figueroa F, Klein J: Alu elements of the primate major histocompatibility complex. Mamm Genome 5:405–415 (1994).
41.
Ono, M, Yasunaga T, Miyata T, Ushikubo H: Nucleotide sequence of human endogenous retrovirus genome related to the mouse mammary tumor virus genome. J Virol 60: 589–598 (1986).
42.
Ota M, Bahram S, Katsuyama Y, Saito S, Nose Y, Sada M, Ando H, Inoko H: On the MICA deleted-MICB null, HLA-B*4801 haplotype. Tissue Antigens 56:268–271 (2000).
43.
Pichon L, Carn G, Bouric P, Giffon T, Chauvel B, Lepourcelet M, Mosser J, Legall J-V, David V: Structural analysis of the HLA-A/HLA-F subregion: precise localization of two new multigene families closely associated with the HLA class I sequences. Genomics 32:236–244 (1996).
44.
Schwartz S, Zhang Z, Frazer KA, Smit A, Riemer C, Bouck J, Gibbs R, Hardison R, Miller W: PipMaker – a webserver for aligning two genomic DNA sequences. Genome Res 10:577–586 (2000).
45.
Shen L, Wu L, Sanlioglu S, Chen R, Mendoza AR, Dangel AW, Carroll MC, Zipf WB, Yu CY: Structure and genetics of the partially duplicated gene RP located immediately upstream of the complement C4A and C4B Genes on the HLA Class III Region. J Biol Chem 269:8466–8476 (1994).
46.
Shiina T, Tamiya A, Oka A, Yamagata T, Yamagata N, Kikkawa E, Goto A, Mizuki N, Watanabe K, Fukuzumi Y, Taguchi S, Sugawara C, Ono A, Chen L, Yamazaki M, Tashiro H, Ando A, Ikemura T, Kimura M, Inoko H: Nucleotide sequencing analysis of the 146-kilobase segment around the IkBL and MICA g enes at the centromeric end of the HLA Class I region. Genomics 47:372–382 (1998).
47.
Shiina T, Tamiya G, Oka A, Takishima N, Inoko H: Genome sequence analysis of the 1.8 Mb entire human MHC class I region. Immunol Rev 176:193–199 (1999a).
48.
Shiina T, Tamiya G, Oka A, Takishima N, Yamagata T, Kikkawa E, Iwata K, Tomizawa M, Okuaki N, Kuwano Y, Watanabe 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: Molecular dynamics of MHC genesis unraveled by sequence analysis of the 1,796,938-bp HLA class I region. Proc Natl Acad Sci USA 96:13282–13287 (1999b).
49.
Sonnhammer EL, Durbin R: A dot-matrix program with dynamic threshold control suited for genomic DNA and protein sequence analysis. Gene 167:GC1–10 (1995).
50.
Smit AFA: Identification of a new, abundant superfamily of mammalian LTR-transposons. Nucleic Acids Res 21:1863–1872 (1993).
51.
Smit AFA: The origin of interspersed repeats in the human genome. Curr Opin Genet Devel 6:743–748 (1996).
52.
Smit AFA: Interspersed repeats and other momentos of transposable elements in the human genome. Curr Opin Genet Devel 9:657–663 (1999).
53.
Smit AFA: Charlie9. RepBase Update 8.1 (2001).
54.
Smit AFA, Riggs AD: Tiggers and other DNA transposon fossils in the human genome. Proc Natl Acad Sci USA 93:1443–1448 (1996).
55.
Thompson JD, Gidson TJ, Plewniak F, Jeanmougin F, Higgins DG: The ClustalX-Windows interface: Flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25:4876–4882 (1997).
56.
Toda Y, Tomita M: Alu elements as an aid in deciphering genome rearrangements. Gene 205:173–176 (1997).
57.
Vernet C, Ribouchon MT, Chimini G, Jouanolle AM, Sidibe I, Pontarotti P: A novel coding sequence belonging to a new multicopy gene family mapping within the human MHC class I region. Immunogenetics 38:47–53 (1993).
58.
Vernet C, Ribouchon MT, Chimini G, Pontarotti P: Structure and evolution of a member of a new subfamily of GTP-binding proteins mapping to the human MHC class I region. Mamm Genome 5:100–105 (1994).
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.