Abstract
Modo-UG is a class I gene located in the MHC of the marsupial Monodelphis domestica, the gray, short-tailed opossum. Modo-UG is expressed as three alternatively spliced mRNA forms, all of which encode a transmembrane form with a short cytoplasmic tail that lacks phosphorylation sites typically found in classical class I molecules. The three alternative mRNAs would encode a full-length form, an isoform lacking the α2 domain, and one lacking both α2 and α3 domains. Genotyping both captive-bred and wild M. domestica from different geographic regions revealed no variation in the residues that make up Modo-UG’s peptide-binding groove. Modo-UG’s low polymorphism is contrasting to that of a nearby class I locus, Modo-UA1, which has a highly polymorphic peptide-binding region. Absence of functional polymorphism in Modo-UG is therefore not a general feature of opossum class I genes but the result of negative selection. Modo-UG is the first MHC linked marsupial class I to be described that appears to clearly have nonclassical features.
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References
Allen RL, O’Callaghan CA, McMichael AJ, Bowness P (1999) HLA-B27 can form a novel β2-microglobulin-free heavy chain homodimer structure. J Immunol 162:5045–5048
Belov K, Deakin J, 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 JAM, Miller RD (2006) Reconstructing an ancestral mammalian immune supercomplex from a marsupial MHC. PLoS Biol 4:e46
Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC (1987) Structure of the human class I histocompatibility antigen, HLA-A2. Nature 329:506–512
Boyson JE, Iwanga KK, Golos TG, Watkins DI (1997) Identification of a novel MHC class I gene, Mamu-AG, expressed in the placenta of a primate with an inactivated G locus. J Immunol 159:3311–3321
Boyson JE, Iwanga KK, Urvater A, Hughes AL, Golos TG, Watkins DI (1999) Evolution of a new nonclassical MHC class I locus in two Old World primate species. Immunogenetics 49:86–98
Boyson JE, Erskine R, Whitman MC, Chiu M, Lau JM, Koopman LA, Valter MM, Angelisova P, Horejsi V, Strominger JL (2002) Disulfide bond-mediated dimerization of HLA-G on the cell surface. Proc Natl Acad Sci USA 99:16180–16185
Castro MJ, Morales P, Rojo-Amigo R, Martinez-Laso J, Allende L, Varela P, Garcia-Berciano M, Guillen-Perales J, Arnaiz-Villena A (2000) Homozygous HLA-G*0105N individuals indicate that membrane anchored HLA-G1 molecule is not necessary for survival. Tissue Antigens 56:232–239
Geraghty DE, Koller BH, Orr HT (1987) A human major histocompatibility complex class I gene that encodes a protein with a shortened cytoplasmic domain. Proc Natl Acad Sci USA 84:9145–9149
Gonen-Gross T, Achdout H, Gazit R, Hanna J, Mizrahi S, Markel G, Goldman-Wohl D, Yagel S, Horejsi V, Levy O, Baniyash M, Mandelboim O (2003) Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 function. J Immunol 171:1343–1351
Gouin N, Deakin J, Miska KB, Miller RD, Kammerer CM, Graves JAM, VandeBerg JL, Samollow PB (2006) Linkage mapping and physical localization of the major histocompatibility complex region of the marsupial Monodelphis domestica. Cytogenet Genome Res 112(3–4):277–285
Guidry PA, Stroynowski I (2005) The murine family of gut-restricted class Ib MHC includes alternatively spliced isoforms of the proposed HLA-G homolog, “blastocyst MHC”. J Immunol 175:5248–5259
Kaufman J, Salomonsen J, Flajnik M (1994) Evolutionary conservation of MHC class I and class II molecules—different yet the same. Semin Immunol 6:411–424
Kumar S, Hedges SB (1998) A molecular timescale for vertebrate evolution. Nature 392:917–920
Kumar S, Tamura K, Nei M (2004) MEGA3: integrated software for molecular evolutionary genetics analysis and sequence alignment. Brief Bioinform 5:150–163
Langat DK, Morales PJ, Fazleabas AT, Mwenda JM, Hunt JS (2002) Baboon placentas express soluble and membrane bound Paan-AG proteins encoded by alternative spliced transcripts of the class Ib major histocompatibility complex gene, Paan-AG. Immunogenetics 54:164–173
LeMaoult J, Le Discorde M, Rouas-Freiss N, Moreau P, Menier C, McCluskey J, Carosella ED (2003) Biology and functions of human leukocyte antigen-G in health and sickness. Tissue Antigens 62:273–284
Mandelboim O, Reyburn HT, ValesGomez M, Pazmany L, Colonna M, Borsellino G, Strominger JL (1996) Protection from lysis by natural killer cells of group 1 and 2 specificity is mediated by residue 80 in human histocompatibility leukocyte antigen C alleles and also occurs with empty major histocompatibility complex molecules. J Exp Med 184:913–922
Marsh SGE, Parham P, Barber LD (2000) The HLA factsbook. Academic, San Diego, CA
Miller MM, Wabg C, Parisini E, Coletta RD, Goto RM, Lee SY, Barral DC, Townes M, Roura-Mir C, Ford HL, Brenner MB, Dascher CC (2005) Characterization of two avian MHC-like genes reveals and ancient origin of the CD1 family. Proc Natl Acad Sci USA 102:8647–8679
Miska KB, Miller RD (1999) Marsupial Mhc class I: classical sequences from the opossum, Monodelphis domestica. Immunogenetics 50:89–93
Miska KB, Wright AM, Lundgren R, Sasaki-McClees R, Osterman A, Gale JM, Miller RD (2004) Analysis of a marsupial MHC region containing two recently duplicated class I loci. Mamm Genome 15:851–864
Moreau P, Dausset J, Carosella ED, Rouas-Freiss N (2002) Viewpoint on the functionality of the human leukocyte antigen-G null allele at the fetal-maternal interface. Biol Reprod 67:1375–1378
Nilsson T, Jackson M, Peterson PA (1989) Short cytoplasmic sequences serve as retention signals for transmembrane proteins in the endoplasmic reticulum. Cell 58:707–718
Parham P (1994) The rise and fall of great class I genes. Semin Immunol 6:373–382
Park B, Lee S, Kim E, Chang S, Jin M, Ahn K (2001) The truncated cytoplasmic tail of HLA-G serves as a quality-control function in post-ER compartments. Immunity 15:213–224
Rodger JC, Fletcher TP, Tyndale-Biscoe CH (1985) Active anti-paternal immunization does not affect the success of marsupial pregnancy. J Reprod Immunol 8:249–256
Rouas-Freiss N, Marchal RE, Kirszenbaum M, Dausset J, Carosella ED (1997) The α1 domain of HLA-G1 and HLA-G2 inhibits cytotoxicity induced by natural killer cells: Is HLA-G the public ligand for natural killer cell inhibitory receptors? Proc Natl Acad Sci USA 94:5249–5254
Ryan AF, Grendell RL, Geraghty DE, Golos TG (2002) A soluble isoform of the rhesus monkey nonclassical MHC class I molecule Mamu-AG is expressed in the placenta and testis. J Immunol 169:673–683
Salomonsen J, Sorenson MR, Marston DA, Rogers SL, Collen T, van Hateren A, Smith AL, Beal RK, Skjodt K, Kaufman J (2005) Two CD1 genes map to the chicken MHC, indicating that CD1 genes are ancient and likely to have been present in the primordial MHC. Proc Natl Acad Sci USA 102:8668–8673
Samples NK, Vandeberg JL, Stone WH (1986) Passively acquired immunity in the newborn of a marsupial (Monodelphis domestica). Am J Reprod Immunol Microbiol 11:94–97
Sipes SL, Medaglia MV, Stabely DL, DeBruyn CS, Alden MS, Catenacci V, Landel CP (1996) A new major histocompatibility complex class Ib gene expressed in the mouse blastocyst and placenta. Immunogenetics 45:108–120
Stone WH, Manis GS, Hoffman ES, Saphire DG, Hubbard GB, VandeBerg JL (1997) Fate of allogeneic skin transplantations in a marsupial (Monodelphis domestica). Lab Anim Sci 47:283–287
Stroynowski I, Tabaczewski P (1996) Multiple products of class Ib Qa-2 genes which ones are functional? Res Immunol 147:290–298
VandeBerg JL, Robinson ES (1997) The laboratory opossum (Monodelphis domestica) in biomedical research. In: Saunders NR, Hinds LA (eds) Marsupial Biology: recent research, new perspectives. University of New South Wales Press, Sydney, pp 238–253
Van Oorshot RA, Cooper DW (1988) Lack of evidence for complement-dependent cytotoxic antibodies to fetal paternally derived antigens in the marsupial Macropus eugenii (tammar wallaby). Am J Reprod Immunol 17:145–148
Walker KZ, Tyndale-Biscoe CH (1978) Immunogical aspects of gestation in the tammar wallaby, Macropus eugenii. Aust J Zool 31:173–182
Waneck GL, Sherman DH, Kincade PW, Low MG, Flavell RA (1988) Molecular mapping of signals in the Qa-2 antigen required for attachment of the phosphatidylinositol membrane anchor. Proc Natl Acad Sci USA 85:577–581
West AP, Herr AB, Bjorkman PJ (2004) The chicken yolk sac IgY receptor, a functional equivalent of the mammalian MHC-related Fc receptor, is a phospholipase A2 receptor homolog. Immunity 20:601–610
Woodburne MO, Rich TH, Springer MS (2003) The evolution of tribospheny and the antiquity of mammalian clades. Mol Phylogenet Evol 28:360–385
Acknowledgements
The authors thank Dr. John VandeBerg and the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation for providing captive-bred M. domestica and the Museum of Southwestern Biology, University of New Mexico, for providing tissues from wild-caught, Bolivian M. domestica. This work was supported by grants from the National Science Foundation (MCB-0234930) to R. D. M., NIH Institute Development Award Program of the National Center for Research Resources (P20 RR18754) to M. L. B. and R. D. M, NIH grant (RR-014214) to P. B. S, and Southwest Foundation Forum Grant to N. G. Nicolas Gouin and April M. Wright contributed equally to this work.
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Alleles of Modo-UG present for 14 captive-bred Brazilian and 16 wildcaught Bolivian M. domestica genotyped (PDF 50 kb)
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Gouin, N., Wright, A.M., Miska, K.B. et al. Modo-UG, a marsupial nonclassical MHC class I locus. Immunogenetics 58, 396–406 (2006). https://doi.org/10.1007/s00251-006-0115-4
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DOI: https://doi.org/10.1007/s00251-006-0115-4