Mammalian Genome

, Volume 15, Issue 10, pp 851–864 | Cite as

Analysis of a marsupial MHC region containing two recently duplicated class I loci

  • Katarzyna B. Miska
  • April M. Wright
  • Rachel Lundgren
  • Robert Sasaki–McClees
  • Amy Osterman
  • James M. Gale
  • Robert D. Miller


A 37-kb cosmid containing two complete major histocompatibility complex (MHC) class I α chain loci from the opossum Monodelphis domestica was isolated, fully sequenced, and characterized. This sequence represents the largest contiguous genomic sequence reported for the MHC region of a nonplacental mammal. Based on particular conserved amino acid residues, and limited expression analyses, the two MHC-I loci, designated ModoUB and ModoUC, appear to encode functional MHC-I molecules. The two coding regions are 98% identical at the nucleotide level; however, their promoter regions differ significantly. Two CpG islands present in the cosmid sequence correspond to the two coding regions. Twelve microsatellites and six retroelements were also present in the cosmid. The retroelements share highest sequence homology to the CORE–SINE family of retroelements. Due to high sequence identity, it is very likely that ModoUB and ModoUC loci are products of recent gene duplication that occurred less than 4 million years ago.


  1. Altschul, SF, Gish, W, Miller, W, Myers, EW, Lipman, DJ 1990Basic local alignment search toolJ Mol Biol215403410CrossRefPubMedGoogle Scholar
  2. Bingulac–Popovic, J, Figueroa, F, Sato, A, Talbot, WS, Johnson, SL,  et al. 1997Mapping of mhc class I and class II regions to different linkage groups in the zebrafish, Danio rerioImmunogenetics46129134CrossRefPubMedGoogle Scholar
  3. Burke, TW, Kadonga, JT 1996Drosophila TFIID binds to a conserved downstream basal promoter element that is present in many TATA-deficient promotersGenes Dev10711724PubMedGoogle Scholar
  4. Dennis, C 2003Opossum hops over kangaroo to top genome listNature425753CrossRefGoogle Scholar
  5. Felsenstein, J 1981Evolutionary trees from DNA sequences: a maximum likelihood approachJ Mol Evol17368376PubMedGoogle Scholar
  6. Fitch, WM 1971Toward defining the course of evolution: Minimum change for a specific tree topologySyst Zool20406416Google Scholar
  7. Gilbert, N, Labuda, D 1999CORE–SINEs: Eukaryotic short interspersed retroposing elements with common sequence motifsProc Natl Acad Sci USA9628692874CrossRefPubMedGoogle Scholar
  8. Gilbert, N, Labuda, D 2000Evolutionary inventions and continuity of CORE–SINEs in mammalsJ Mol Biol298365377CrossRefPubMedGoogle Scholar
  9. Gorer, PA 1937The genetic and antigenic basis of tumour transplantationJ Pathol Bacteriol44691697Google Scholar
  10. Gorer, PA, Lyman, S, Snell, GD 1948Studies on the genetic and antigenic basis of tumour transplantation, linkage between a histocompatibility gene and ‘fused’ in miceProc R Soc London B Biol Sci135499505Google Scholar
  11. Guild, BC, Strominger, JL 1984Human and murine class I MHC antigens conserved serine 335, the site of HLA phosphorylation in vivoJ Biol Chem25992359240PubMedGoogle Scholar
  12. Guild, BC, Erikson, RL, Strominger, JL 1983HLA-A2 and HLA-B7 antigens are phosphorylated in vitro by Rous sarcoma virus kinase (pp60V-src) at a tyrosine residue encoded in a highly conserved exon of the intracellular domainProc Natl Acad Sci USA9128942898Google Scholar
  13. Günther, E, Walter, L 2001The major histocompatibility complex of the rat (Rattus norvegicus)Immunogenetics53520542CrossRefPubMedGoogle Scholar
  14. Hansen, JD, Strassburger, P, Thorgaard, GH, Young, WP, Du Pasquier, L 1999Expression, linkage, and polymorphism of MHC-related genes in rainbow trout, Oncorhynchus mykissJ Immunol163774786PubMedGoogle Scholar
  15. Hughes, AL, Nei, M 1988Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selectionNature335167170CrossRefPubMedGoogle Scholar
  16. Janke, A, Xu, X, Arnason, U 1997The complete mitochondrial genome of the wallaroo (Macropus robustus) and the phylogenetic relationship among Monotremata, Marsupiala, and EutheriaProc Natl Acad Sci USA9412761281CrossRefPubMedGoogle Scholar
  17. Kaufman, J, Salomonsen, J, Flajnik, M 1994Evolutionary conservation of Mhc class I and II molecules: different yet the sameSemin Immunol6411424CrossRefPubMedGoogle Scholar
  18. Kaufman, J, Milne, S, Gobel, TW, Walker, BA, Jacob, JP,  et al. 1999The chicken B locus is a minimal essential major histocompatibility complexNature401923925CrossRefPubMedGoogle Scholar
  19. Kirsch, JAW, Mayer, GC 1998The platypus is not a rodent: DNA hybridization, amniote phylogeny and the palimpsest theoryPhilos Trans R Soc Lond B Biol Sci35312211237CrossRefPubMedGoogle Scholar
  20. Kirsch, JAW, Lapointe, FJ, Springer, MS 1997DNA studies of marsupials and their implications for metatherian classificationAust J Zool45211280CrossRefGoogle Scholar
  21. Klein, J, Bontrop, RE, Dawkins, RL, Erlich, HA, Gyllensten, UB,  et al. 1990Nomenclature for the major histocompatibility complexes of different species: a proposalImmunogenetics31217219PubMedGoogle Scholar
  22. Kulski, JK, Gaudieri, S, Bellgard, M, Balmer, L, Giles, K,  et al. 1997The evolution of MHC diversity by segmental duplication and transposition of retroelementsJ Mol Evol45599609PubMedGoogle Scholar
  23. Kumar, S, Hedges, SB 1998A molecular timescale for vertebrate evolutionNature392917920CrossRefPubMedGoogle Scholar
  24. Larsen, F, Gundersen, G, Lopez, R, Prydz, H 1992CpG islands as gene markers in the human genomeGenomics1310951107CrossRefPubMedGoogle Scholar
  25. MHC Sequencing Consortium,  1999Complete sequence and gene map of a human major histocompatibility complexNature401921923CrossRefPubMedGoogle Scholar
  26. Miska, KB, Miller, RD 1999Marsupial Mhc class I: classical sequences from the opossum, Monodelphis domesticaImmunogenetics508993CrossRefPubMedGoogle Scholar
  27. Miska, KB, Harrison, GH, Hellman, L, Miller, RD 2002The major histocompatibility complex in monotremes: An analysis of the evolution of Mhc class I genes across all three mammalian subclassesImmunogenetics54381393CrossRefPubMedGoogle Scholar
  28. Nei, M, Gu, X, Sitnikova, T 1997Evolution by the birth-and-death process in multigene families of the vertebrate immune systemProc Natl Acad Sci USA9477997806CrossRefPubMedGoogle Scholar
  29. Ohta, Y, Okamura, K, McKinney, EC, Bartl, S, Hashimoto, K,  et al. 2000Primitive synteny of vertebrate major histocompatibility complex class I and class II genesProc Natl Acad Sci USA9747124717CrossRefPubMedGoogle Scholar
  30. Parham, P, Lawlor, DA, Lomen, CE, Ennis, PD 1989Diversity and diversification of HLA-A, B, C allelesJ Immunol14239373950PubMedGoogle Scholar
  31. Patton, JL, dos Reis, SF, da Silva, MNF 1996Relationships among didelphid marsupials based on sequence variation in the mitochondrial cytochrome B geneJ Mamm Evol3329Google Scholar
  32. Posada, D, Crandall, KA 1998MODELTEST: testing the model of DNA substitutionBioinformatics14817818CrossRefPubMedGoogle Scholar
  33. Renard, C, Vaiman, M, Chiannilkulchai, N, Cattolico, L, Robert, C,  et al. 2001Sequence of the pig major histocompatibility region containing the classical class I genesImmunogenetics53490500CrossRefPubMedGoogle Scholar
  34. Retief, JD, Krajewski, C, Westerman, M, Winkfein, RJ, Dixon, GH 1995Molecular phylogeny and evolution of marsupial protamine PI genesProc R Soc Lond B Biol Sci259714PubMedGoogle Scholar
  35. Saitou, N, Nei, M 1987The neighbor joining method: a new method for reconstructing phylogenetic treesMol Biol Evol4406425PubMedGoogle Scholar
  36. Salter, R, Benjamin, R, Wesley, P, Buxton, S, Garret, T,  et al. 1990A binding site for the T cell co-receptor CD8 on the α3 domain of HLA-A2Nature3454146CrossRefPubMedGoogle Scholar
  37. Samollow, PB, Marshall–Graves, JA 1998Gene maps of marsupialsILAR J39203224PubMedGoogle Scholar
  38. Saper, MA, Bjorkman, PJ, Wiley, DC 1991Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 Å resolutionJ Mol Biol219277319PubMedGoogle Scholar
  39. Shiina, T, Tamiya, G, Oka, A, Takishima, N, Yamagata, T,  et al. 1999Molecular dynamics of MHC genesis unraveled by sequence analysis of the 1,796,938-bp HLA class I regionProc Natl Acad Sci USA961328213287CrossRefPubMedGoogle Scholar
  40. Solier, C, Mallet, V, Lenfant, F, Bertrand, A, Huchenq, A,  et al. 2001HLA-G unique promoter region: functional implicationsImmunogenetics53617625CrossRefPubMedGoogle Scholar
  41. Sonnhammer, ELL, Durbin, R 1995A dot-matrix program with dynamic threshold control suited for genomic DNA and protein sequence analysisGene167GC110CrossRefPubMedGoogle Scholar
  42. Swofford, DL 1998PAUP*: Phylogenetic analysis using parsimony (* and other methods), Ver. 4.0 beta: Sinauer)(Sunderland, MA: Sinauer)Google Scholar
  43. Thompson, JD, Higgins, DG, Gibson, TJ 1994CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position specific gap penalties and weight matrix choiceNucleic Acids Res2246734680PubMedGoogle Scholar
  44. Vallejo, AN, Pease, LR 1995Evolution of class I promoter sequences: relationship to function and diversityImmunol Rev143249262PubMedGoogle Scholar
  45. Westerdahl, H, Wittzell, H, Schantz, T 2000Mhc diversity in two passerine birds: no evidence for a minimal essential MhcImmunogenetics5292100CrossRefPubMedGoogle Scholar
  46. Xu, Y, Uberbacher, EC 1997Automated gene identification in large-scale genomic sequencesJ Comput Biol4325338PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Katarzyna B. Miska
    • 1
  • April M. Wright
    • 1
  • Rachel Lundgren
    • 1
  • Robert Sasaki–McClees
    • 1
  • Amy Osterman
    • 1
  • James M. Gale
    • 2
  • Robert D. Miller
    • 1
  1. 1.Department of BiologyThe University of New MexicoAlbuquerque, New MexicoUSA
  2. 2.Department of Cell Biology and PhysiologyThe University of New Mexico School of MedicineAlbuquerqueUSA

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