, Volume 63, Issue 8, pp 485–499 | Cite as

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)

  • Takashi ShiinaEmail author
  • Azumi Kono
  • Nico Westphal
  • Shingo Suzuki
  • Kazuyoshi Hosomichi
  • Yuki F. Kita
  • Christian Roos
  • Hidetoshi Inoko
  • Lutz Walter
Original Paper


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.


Common marmoset MHC Sequencing Diversity Phylogeny Comparative genomics 



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.

Supplementary material

251_2011_526_MOESM1_ESM.pdf (13 kb)
Supplementary Table 1 PCR primer sets for the BAC contig construction (PDF 13 kb)
251_2011_526_MOESM2_ESM.pdf (52 kb)
Supplementary Table 2 Nucleotide similarities with C. jacchus draft assembly (WUGSC 3.2) (PDF 51 kb)
251_2011_526_MOESM3_ESM.pdf (639 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)
251_2011_526_MOESM4_ESM.pdf (135 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)
251_2011_526_MOESM5_ESM.pdf (566 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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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Takashi Shiina
    • 1
    Email author
  • Azumi Kono
    • 1
  • Nico Westphal
    • 2
  • Shingo Suzuki
    • 1
  • Kazuyoshi Hosomichi
    • 3
  • Yuki F. Kita
    • 1
  • Christian Roos
    • 2
  • Hidetoshi Inoko
    • 1
  • Lutz Walter
    • 2
  1. 1.Department of Molecular Life Science, Division of Basic Medical Science and Molecular MedicineTokai University School of MedicineIseharaJapan
  2. 2.Abteilung Primatengenetik, Deutsches PrimatenzentrumLeibniz-Institut für PrimatenforschungGöttingenGermany
  3. 3.Division of Human Genetics, Department of Integrated GeneticsNational Institute of GeneticsShizuokaJapan

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