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Comparative genome analysis of the major histocompatibility complex (MHC) class I B/C segments in primates elucidated by genomic sequencing in common marmoset (Callithrix jacchus)

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Abstract

Common marmoset monkeys (Callithrix jacchus) have emerged as important animal models for biomedical research, necessitating a more extensive characterization of their major histocompatibility complex (MHC) region. However, the genomic information of the marmoset MHC (Caja) is still lacking. The MHC-B/C segment represents the most diverse MHC region among primates. Therefore, in this paper, to elucidate the detailed gene organization and evolutionary processes of the Caja class I B (Caja-B) segment, we determined two parts of the Caja-B sequences with 1,079 kb in total, ranging from H6orf15 to BAT1 and compared the structure and phylogeny with that of other primates. This segment contains 54 genes in total, nine Caja-B genes (Caja-B1 to Caja-B9), two MIC genes (MIC1 and MIC2), eight non-MHC genes, two non-coding genes, and 33 non-MHC pseudogenes that have not been observed in other primate MHC-B/C segments. Caja-B3, Caja-B4, and Caja-B7 encode proper MHC class I proteins according to amino acid structural characteristics. Phylogenetic relationships based on 48 MHC-I nucleotide sequences in primates suggested (1) species-specific divergence for Caja, Mamu, and HLA/Patr/Gogo lineages, (2) independent generation of the “seven coding exon” type MHC-B genes in Mamu and HLA/Patr/Gogo lineages from an ancestral “eight coding exon” type MHC-I gene, (3) parallel correlation with the long and short segmental duplication unit length in Caja and Mamu lineages. These findings indicate that the MHC-B/C segment has been under permanent selective pressure in the evolution of primates.

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References

  • Abbott DH, Barnett DK, Colman RJ, Yamamoto ME, Schultz-Darken NJ (2003) Aspects of common marmoset basic biology and life history important for biomedical research. Comp Med 53:339–350

    PubMed  CAS  Google Scholar 

  • Abi-Rached L, Kuhl H, Roos C, ten Hallers B, Zhu B, Carbone L, de Jong PJ, Mootnick AR, Knaust F, Reinhardt R, Parham P, Walter L (2010) A small, variable, and irregular killer cell Ig-like receptor locus accompanies the absence of MHC-C and MHC-G in gibbons. J Immunol 184:1379–1391

    Article  PubMed  CAS  Google Scholar 

  • Adams EJ, Parham P (2001) Species-specific evolution of MHC class I genes in the higher primates. Immunol Rev 183:41–64

    Article  PubMed  CAS  Google Scholar 

  • Adams EJ, Thomson G, Parham P (1999) Evidence for an HLA-C-like locus in the orangutan Pongo pygmaeus. Immunogenetics 49:865–871

    Article  PubMed  CAS  Google Scholar 

  • Adams AP, Aronson JF, Tardif SD, Patterson JL, Brasky KM, Geiger R, de la Garza M, Carrion R Jr, Weaver SC (2008) Common marmosets (Callithrix jacchus) as a nonhuman primate model to assess the virulence of eastern equine encephalitis virus strains. J Virol 82:9035–9042

    Article  PubMed  CAS  Google Scholar 

  • 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 100:7708–7713

    Article  PubMed  CAS  Google Scholar 

  • Averdam A, Seelke S, Grutzner I, Rosner C, Roos C, Westphal N, Stahl-Hennig C, Muppala V, Schrod A, Sauermann U, Dressel R, Walter L (2007) Genotyping and segregation analyses indicate the presence of only two functional MIC genes in rhesus macaques. Immunogenetics 59:247–251

    Article  PubMed  CAS  Google Scholar 

  • Averdam A, Petersen B, Rosner C, Neff J, Roos C, Eberle M, Aujard F, Munch C, Schempp W, Carrington M, Shiina T, Inoko H, Knaust F, Coggill P, Sehra H, Beck S, Abi-Rached L, Reinhardt R, Walter L (2009) A novel system of polymorphic and diverse NK cell receptors in primates. PLoS Genet 5:e1000688

    Article  PubMed  Google Scholar 

  • Bankiewicz KS, Sanchez-Pernaute R, Oiwa Y, Kohutnicka M, Cummins A, Eberling J (2001) Preclinical models of Parkinson’s disease. Curr Protoc Neurosci Chapter 9:Unit 9 4

  • Cadavid LF, Hughes AL, Watkins DI (1996) MHC class I-processed pseudogenes in New World primates provide evidence for rapid turnover of MHC class I genes. J Immunol 157:2403–2409

    PubMed  CAS  Google Scholar 

  • Cadavid LF, Shufflebotham C, Ruiz FJ, Yeager M, Hughes AL, Watkins DI (1997) Evolutionary instability of the major histocompatibility complex class I loci in New World primates. Proc Natl Acad Sci USA 94:14536–14541

    Article  PubMed  CAS  Google Scholar 

  • Chang H, Wachtman LM, Pearson CB, Lee JS, Lee HR, Lee SH, Vieira J, Mansfield KG, Jung JU (2009) Non-human primate model of Kaposi’s sarcoma-associated herpesvirus infection. PLoS Pathog 5:e1000606

    Article  PubMed  Google Scholar 

  • Daza-Vamenta R, Glusman G, Rowen L, Guthrie B, Geraghty DE (2004) Genetic divergence of the rhesus macaque major histocompatibility complex. Genome Res 14:1501–1515

    Article  PubMed  CAS  Google Scholar 

  • Dewannieux M, Esnault C, Heidmann T (2003) LINE-mediated retrotransposition of marked Alu sequences. Nat Genet 35:41–48

    Article  PubMed  CAS  Google Scholar 

  • Doxiadis GG, Heijmans CM, Otting N, Bontrop RE (2007) MIC gene polymorphism and haplotype diversity in rhesus macaques. Tissue Antigens 69:212–219

    Article  PubMed  CAS  Google Scholar 

  • Ewing B, Green P (1998) Base-calling of automated sequencer traces using phred. II. Error probabilities. Genome Res 8:186–194

    PubMed  CAS  Google Scholar 

  • Ewing B, Hillier L, Wendl MC, Green P (1998) Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res 8:175–185

    PubMed  CAS  Google Scholar 

  • Fukami-Kobayashi K, Shiina T, Anzai T, Sano K, Yamazaki M, Inoko H, Tateno Y (2005) Genomic evolution of MHC class I region in primates. Proc Natl Acad Sci USA 102:9230–9234

    Article  PubMed  CAS  Google Scholar 

  • Furlan R, Cuomo C, Martino G (2009) Animal models of multiple sclerosis. Methods Mol Biol 549:157–173

    Article  PubMed  CAS  Google Scholar 

  • Gaytan F, Gaytan M, Castellano JM, Romero M, Roa J, Aparicio B, Garrido N, Sanchez-Criado JE, Millar RP, Pellicer A, Fraser HM, Tena-Sempere M (2009) KiSS-1 in the mammalian ovary: distribution of kisspeptin in human and marmoset and alterations in KiSS-1 mRNA levels in a rat model of ovulatory dysfunction. Am J Physiol Endocrinol Metab 296:E520–E531

    Article  PubMed  CAS  Google Scholar 

  • Guindon S, Gascuel O (2003) A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 52:696–704

    Article  PubMed  Google Scholar 

  • Hattori F, Chen H, Yamashita H, Tohyama S, Satoh YS, Yuasa S, Li W, Yamakawa H, Tanaka T, Onitsuka T, Shimoji K, Ohno Y, Egashira T, Kaneda R, Murata M, Hidaka K, Morisaki T, Sasaki E, Suzuki T, Sano M, Makino S, Oikawa S, Fukuda K (2010) Nongenetic method for purifying stem cell-derived cardiomyocytes. Nat Methods 7:61–66

    Article  PubMed  CAS  Google Scholar 

  • Kametani Y, Suzuki D, Kohu K, Satake M, Suemizu H, Sasaki E, Ito T, Tamaoki N, Mizushima T, Ozawa M, Tani K, Kito M, Arai H, Koyanagi A, Yagita H, Habu S (2009) Development of monoclonal antibodies for analyzing immune and hematopoietic systems of common marmoset. Exp Hematol 37:1318–1329

    Article  PubMed  CAS  Google Scholar 

  • Kap YS, Smith P, Jagessar SA, Remarque E, Blezer E, Strijkers GJ, Laman JD, Hintzen RQ, Bauer J, Brok HP, t Hart BA (2008) Fast progression of recombinant human myelin/oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis in marmosets is associated with the activation of MOG34-56-specific cytotoxic T cells. J Immunol 180:1326–1337

    PubMed  CAS  Google Scholar 

  • Knapp LA, Cadavid LF, Watkins DI (1998) The MHC-E locus is the most well conserved of all known primate class I histocompatibility genes. J Immunol 160:189–196

    PubMed  CAS  Google Scholar 

  • Layne DG, Power RA (2003) Husbandry, handling, and nutrition for marmosets. Comp Med 53:351–359

    PubMed  CAS  Google Scholar 

  • Lever MS, Stagg AJ, Nelson M, Pearce P, Stevens DJ, Scott EA, Simpson AJ, Fulop MJ (2008) Experimental respiratory anthrax infection in the common marmoset (Callithrix jacchus). Int J Exp Pathol 89:171–179

    Article  PubMed  Google Scholar 

  • Ludlage E, Mansfield K (2003) Clinical care and diseases of the common marmoset (Callithrix jacchus). Comp Med 53:369–382

    PubMed  CAS  Google Scholar 

  • Mansfield K (2003) Marmoset models commonly used in biomedical research. Comp Med 53:383–392

    PubMed  CAS  Google Scholar 

  • 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, Ando A, Ikemura T, Inoko H (1997) 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

    Article  PubMed  CAS  Google Scholar 

  • Nei M, Gu X, Sitnikova T (1997) Evolution by the birth-and-death process in multigene families of the vertebrate immune system. Proc Natl Acad Sci USA 94:7799–7806

    Article  PubMed  CAS  Google Scholar 

  • Nelson M, Lever MS, Savage VL, Salguero FJ, Pearce PC, Stevens DJ, Simpson AJ (2009) Establishment of lethal inhalational infection with Francisella tularensis (tularaemia) in the common marmoset (Callithrix jacchus). Int J Exp Pathol 90:109–118

    Article  PubMed  Google Scholar 

  • Posada D, Crandall KA (1998) MODELTEST: testing the model of DNA substitution. Bioinformatics 14:817–818

    Article  PubMed  CAS  Google Scholar 

  • Ronquist F, Huelsenbeck JP (2003) MrBayes 3: bayesian phylogenetic inference under mixed models. Bioinformatics 19:1572–1574

    Article  PubMed  CAS  Google Scholar 

  • Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425

    PubMed  CAS  Google Scholar 

  • Sasaki E, Hanazawa K, Kurita R, Akatsuka A, Yoshizaki T, Ishii H, Tanioka Y, Ohnishi Y, Suemizu H, Sugawara A, Tamaoki N, Izawa K, Nakazaki Y, Hamada H, Suemori H, Asano S, Nakatsuji N, Okano H, Tani K (2005) Establishment of novel embryonic stem cell lines derived from the common marmoset (Callithrix jacchus). Stem Cells 23:1304–1313

    Article  PubMed  CAS  Google Scholar 

  • Sasaki E, Suemizu H, Shimada A, Hanazawa K, Oiwa R, Kamioka M, Tomioka I, Sotomaru Y, Hirakawa R, Eto T, Shiozawa S, Maeda T, Ito M, Ito R, Kito C, Yagihashi C, Kawai K, Miyoshi H, Tanioka Y, Tamaoki N, Habu S, Okano H, Nomura T (2009) Generation of transgenic non-human primates with germline transmission. Nature 459:523–527

    Article  PubMed  CAS  Google Scholar 

  • Schultz-Darken NJ (2003) Sample collection and restraint techniques used for common marmosets (Callithrix jacchus). Comp Med 53:360–363

    PubMed  CAS  Google Scholar 

  • Shiina T, Tamiya G, Oka A, Yamagata T, Yamagata N, Kikkawa E, Goto K, 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 (1998) Nucleotide sequencing analysis of the 146-kilobase segment around the IkBL and MICA genes at the centromeric end of the HLA class I region. Genomics 47:372–382

    Article  PubMed  CAS  Google Scholar 

  • 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 (1999) 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

    Article  PubMed  CAS  Google Scholar 

  • Shiina T, Inoko H, Kulski JK (2004) An update of the HLA genomic region, locus information and disease associations: 2004. Tissue Antigens 64:631–649

    Article  PubMed  CAS  Google Scholar 

  • Shiina T, Ota M, Shimizu S, Katsuyama Y, Hashimoto N, Takasu M, Anzai T, Kulski JK, Kikkawa E, Naruse T, Kimura N, Yanagiya K, Watanabe A, Hosomichi K, Kohara S, Iwamoto C, Umehara Y, Meyer A, Wanner V, Sano K, Macquin C, Ikeo K, Tokunaga K, Gojobori T, Inoko H, Bahram S (2006) Rapid evolution of major histocompatibility complex class I genes in primates generates new disease alleles in humans via hitchhiking diversity. Genetics 173:1555–1570

    Article  PubMed  CAS  Google Scholar 

  • Shiina T, Hosomichi K, Inoko H, Kulski JK (2009) The HLA genomic loci map: expression, interaction, diversity and disease. J Hum Genet 54:15–39

    Article  PubMed  CAS  Google Scholar 

  • Specht A, DeGottardi MQ, Schindler M, Hahn B, Evans DT, Kirchhoff F (2008) Selective downmodulation of HLA-A and -B by Nef alleles from different groups of primate lentiviruses. Virology 373:229–237

    Article  PubMed  CAS  Google Scholar 

  • Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599

    Article  PubMed  CAS  Google Scholar 

  • Tardif SD, Smucny DA, Abbott DH, Mansfield K, Schultz-Darken N, Yamamoto ME (2003) Reproduction in captive common marmosets (Callithrix jacchus). Comp Med 53:364–368

    PubMed  CAS  Google Scholar 

  • Weatherford T, Chavez D, Brasky KM, Lanford RE (2009) The marmoset model of GB virus B infections: adaptation to host phenotypic variation. J Virol 83:5806–5814

    Article  PubMed  CAS  Google Scholar 

  • Yaguchi M, Tabuse M, Ohta S, Ohkusu-Tsukada K, Takeuchi T, Yamane J, Katoh H, Nakamura M, Matsuzaki Y, Yamada M, Itoh T, Nomura T, Toyama Y, Okano H, Toda M (2009) Transplantation of dendritic cells promotes functional recovery from spinal cord injury in common marmoset. Neurosci Res 65:384–392

    Article  PubMed  Google Scholar 

  • Zuhlke U, Weinbauer G (2003) The common marmoset (Callithrix jacchus) as a model in toxicology. Toxicol Pathol 31(Suppl):123–127

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank Keiko Tanaka, Kazuyo Yanagiya, and Satoko Kintou of the Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine for the technical assistance. The work was supported by the Scientific Research on Priority Areas “Comparative Genomics” (20017023) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) and Grant-in-Aid for Scientific Research (B) (21300155) from Japan Society for the Promotion of Science (JSPS), from the program “Pakt für Forschung und Innovation” grant “Biodiversity” of the Leibniz Society and institutional support from the German Primate Center.

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Authors and Affiliations

  1. Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259–1143, Japan

    Takashi Shiina, Azumi Kono, Shingo Suzuki, Yuki F. Kita & Hidetoshi Inoko

  2. Abteilung Primatengenetik, Deutsches Primatenzentrum, Leibniz-Institut für Primatenforschung, Kellnerweg 4, 37077, Göttingen, Germany

    Nico Westphal, Christian Roos & Lutz Walter

  3. Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka, 411–8540, Japan

    Kazuyoshi Hosomichi

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  1. Takashi Shiina
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Correspondence to Takashi Shiina.

Additional information

The nucleotide sequence data reported in this paper have been submitted to the DDBJ, EMBL, and GenBank nucleotide sequence databases and have been assigned accession numbers AB600201 and AB600202.

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Supplementary Table 1

PCR primer sets for the BAC contig construction (PDF 13 kb)

Supplementary Table 2

Nucleotide similarities with C. jacchus draft assembly (WUGSC 3.2) (PDF 51 kb)

Supplementary Fig. 1

Estimated amino acid comparison among primate MHC-B and MHC-C genes. 1, 2, 3, 8, b, v, S, CHO indicate α1 domain contact site, α2 domain contact site, α3 domain contact site, CD8 contact site, beta 2 microglobulin (B2M) contact site, T cell receptor and peptide contact site, disulfide bond site, and glycosyl site, respectively. Yellow, red, orange, and blue background indicate α1, α2, α3, CD8, B2M contact sites, variable sites, both of the contact sites, and variable sites and disulfide bond and glycosyl sites, respectively. An asterisk indicates a termination codon (PDF 639 kb)

Supplementary Fig. 2

Nucleotide sequence-based phylogenetic trees. (A1) and (A2) indicate phylogenetic trees on exon 4 to exon 8 of the MHC-I genes constructed by NJ and BI methods, respectively. (B1) and (B2) indicate phylogenetic trees on intron sequences of the MHC-I genes constructed by NJ and BI methods, respectively. Red, blue, and black gene names and boxes indicate seven exon type MHC-I genes, eight exon type MHC-B/C genes, and pseudogenes, respectively. Numbers around the branches indicate bootstrap values in NJ method and posterior probabilities in BI method (PDF 135 kb)

Supplementary Fig. 3

Dot matrix images between the MHC-B/C segment from the POU5F1 and BAT1 versus itself such as 126 kb mouse lemur (A), 1,002 kb common marmoset (B), 1,298 kb rhesus macaque (C), 280 kb gorilla (D), 294 kb chimpanzee and 364 kb human. Red, blue, and black gene names indicate seven exon type MHC-B genes, eight exon type MHC-B and MHC-C genes and pseudogenes, respectively. Gray gene names and boxes indicate MIC and non-MHC genes (PDF 566 kb)

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Shiina, T., Kono, A., Westphal, N. et al. Comparative genome analysis of the major histocompatibility complex (MHC) class I B/C segments in primates elucidated by genomic sequencing in common marmoset (Callithrix jacchus). Immunogenetics 63, 485–499 (2011). https://doi.org/10.1007/s00251-011-0526-8

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