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Characterisation of major histocompatibility complex class I genes at the fetal-maternal interface of marsupials

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Abstract

Major histocompatibility complex class I molecules (MHC-I) are expressed at the cell surface and are responsible for the presentation of self and non-self antigen repertoires to the immune system. Eutherian mammals express both classical and non-classical MHC-I molecules in the placenta, the latter of which are thought to modulate the maternal immune response during pregnancy. Marsupials last shared a common ancestor with eutherian mammals such as humans and mice over 160 million years ago. Since, like eutherians, they have an intra-uterine development dependent on a placenta, albeit a short-lived and less invasive one, they provide an opportunity to investigate the evolution of MHC-I expression at the fetal-maternal interface. We have characterised MHC-I mRNA expression in reproductive tissues of the tammar wallaby (Macropus eugenii) from the time of placental attachment to day 25 of the 26.5 day pregnancy. Putative classical MHC-I genes were expressed in the choriovitelline placenta, fetus, and gravid endometrium throughout the whole of this period. The MHC-I classical sequences were phylogenetically most similar to the Maeu-UC (50/100 clones) and Maeu-UA genes (7/100 clones). Expression of three non-classical MHC-I genes (Maeu-UD, Maeu-UK and Maeu-UM) were also present in placental samples. The results suggest that expression of classical and non-classical MHC-I genes in extant marsupial and eutherian mammals may have been necessary for the evolution of the ancestral therian placenta and survival of the mammalian fetus at the maternal-fetal interface.

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Abbreviations

MHC-I:

Major histocompatibility complex class I

PBR:

Protein binding region

α1/2:

Alpha 1 and 2 domain

BOM:

Bilaminar omphalopleure

TOM:

Trilaminar omphalopleure

cDNA:

Complimentary DNA

References

  • Amoroso EC (1959) Comparative anatomy of the placenta. Ann N Y Acad Sci 73:855–872

    Article  Google Scholar 

  • Andrews DM, Sullivan LC, Baschuk N, Chan CJ, Berry R, Cotterell CL, Lin J, Halse H, Watt SV, Pousine-Larent J, Wang CR, Scalzo AA, Yokoyama WM, Rossjohn J, Brooks AG, Smyth MJ (2012) Recognition of the non-classical class I molecule H2-M3 by the receptor Ly49A regulates the licensing and activation of NK cells. Nature Immunol 13:1171–1177

    Article  CAS  Google Scholar 

  • Bainbridge DRJ (2000) Evolution of mammalian pregnancy in the presence of the maternal immune system. Rev Reprod 5:67–74

    Article  CAS  PubMed  Google Scholar 

  • Baker ML, Melman D, Huntley J, Miller RD (2008) Evolution of the opossum major histocompatibility complex: evidence for diverse alternative splice patterns and low polymorphism among class I genes. Immunol 128:e418–e431

    Article  Google Scholar 

  • Belov K, Deakin JE, 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 JA, Miller RD (2006) Reconstructing an ancestral mammalian immune supercomplex from a marsupial major histocompatibility complex. PLoS Biol 4, e46

    Article  PubMed Central  PubMed  Google Scholar 

  • Birch J, Murphy L, MacHugh ND, Ellis SA (2006) Generation and maintenance in the cattle MHC class I region. Immunogenetics 58:670–679

    Article  CAS  PubMed  Google Scholar 

  • Bjorkman PJ, Parham P (1990) Structure, function, and diversity of class I major histocompatibility complex molecules. Annu Rev Biochem 59:253–288

    Article  CAS  PubMed  Google Scholar 

  • Blaschitz A, Hutter H, Dohr G (2001) HLA class I protein expression in the human placenta. Early Pregnancy 5:67–69

    CAS  PubMed  Google Scholar 

  • Cao W, Brenner CA, Alikani M, Cohen J, Warner CM (1999) Search for human homologue of the mouse Ped gene. Mol Human Reprod 5:541–547

    Article  CAS  Google Scholar 

  • Chazara O, Xiong S, Moffet A (2011) Maternal KIR and fetal HLA-C: a fine balance. J Leukoc Biol 90:703–716

  • Davies CJ, Fisher PJ, Schlafer DH (1990) Temporal and regional regulation of major histocompatibility complex class I expression at the bovine uterine/placental interface. Placenta 21:194–202

    Article  Google Scholar 

  • Donaldson WL, Zhang CH, Oriol JG, Antczak DF (1990) Invasive equine trophoblast expresses class I major histocompatibility complex antigens. Development 110:63–70

    CAS  PubMed  Google Scholar 

  • Felsenstein J (1985) Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39:783–791

    Article  Google Scholar 

  • Freyer C, Zeller U, Renfree MB (2002) Ultrastructure of the placenta of the tammar wallaby, Macropus eugenii: comparison with the grey short-tailed opossum, Monodelphis domestica. J Anat 201:101–119

    Article  PubMed Central  PubMed  Google Scholar 

  • Gaycken U, Shabahang M, Meyer JN, Glodek P (1994) Molecular characterization of the porcine MHC class I region. Anim Genet 25:537–539

    Google Scholar 

  • Günther E, Walter L (2001) The major histocompatibility complex of the rat (Rattus norvegicus). Immunogenetics 53:520–542

    Article  PubMed  Google Scholar 

  • Gustafson AL, Tallmadge RL, Ramlachlan N, Miller D, Bird H, Antczak DF, Raudsepp T, Chowdhary BP, Skow LC (2003) An ordered BAC contig map of the equine major histocompatibility complex. Cytogenet Genome Res 102:1–4

    Article  Google Scholar 

  • Hedrick PW, Thomson G (1988) Maternal-fetal interactions and the maintenance of HLA polymorphism. Genetics 104:449–456

    Google Scholar 

  • Hickford D, Frankenberg S, Renfree MB (2009) The tammar wallaby, Macropus eugenii: a model kangaroo for the study of developmental and reproductive biology. Cold Spring Harb Protoc 12:449–494

    Google Scholar 

  • Hughes A, Nei M (1988) Pattern of nucleotide substitution at the major histocompatibility complex class I loci reveals overdominant selection. Nature 335:167–170

    Article  CAS  PubMed  Google Scholar 

  • Hulpke S, Tampé R (2013) The MHC I loading complex: a multitasking machinery in adaptive immunity. Trends Biochem Sci 38:412–420

    Article  CAS  PubMed  Google Scholar 

  • Jukes TH, Cantor CR (1969) Evolution of protein molecules. In: Munro HN (ed) Mammalian protein metabolism. Academic, New York, pp 21–132

    Chapter  Google Scholar 

  • Luo ZX, Yuan CX, Meng QJ, Ji Q (2011) A Jurassic eutherian mammal and divergence of marsupials and placentals. Nature 476:442–445

    Article  CAS  PubMed  Google Scholar 

  • Madeja Z, Yadi H, Apps R, Boulenouar S, Roper SJ, Gardner L, Moffett A, Colucci F, Hemberger M (2011) Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth. Proc Natl Acad Sci U S A 108:4012–4017

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Medawar PB (1953) Biological problems of skin surgery. J Int Chir 13:385–391

    CAS  PubMed  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 U S A 94:7799–7806

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nonaka M, Namikawa C, Kato Y, Sasaki M, Salter-Cid L, Flajnick MF (1997) Major histocompatibility complex gene mapping in the amphibian Xenopus implies a primordial organization. Proc Natl Acad Sci U S A 94:5789–5791

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Otting N, Heijmans CM, Noort RC, de Groot NG, Doxiadis GG, van Rood JJ, Watkins DI, Bontrop RE (2005) Unparalleled complexity of the MHC class I region in rhesus macaques. Proc Natl Acad Sci U S A 102:1626–1631

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Parham P, Norman PJ, Abi-Rached L, Hilton HG, Guethlein LA (2012) Review: immunogenetics of human placentation. Placenta 33(Suppl):S71–80

    Article  PubMed Central  PubMed  Google Scholar 

  • Pyo CW, Williams LM, Moore Y, Hyodo H, Li SS, Zhao LP, Sageshima N, Ishitani A, Geraghty DE (2006) HLA-E, HLA-F, and HLA-G polymorphism: genomic sequence defines haplotype structure and variation spanning the non-classical class I genes. Immunogenetics 58:241–251

    Article  CAS  PubMed  Google Scholar 

  • Redman CW, McMichael AJ, Stirrat GM, Sunderland CA, Ting A (1984) Class 1 major histocompatibility complex antigens on human extra-villous trophoblast. Immunology 52:457–488

    CAS  PubMed Central  PubMed  Google Scholar 

  • Renfree MB (1972) Influence of the embryo on the marsupial uterus. Nature 240:475–477

    Article  CAS  PubMed  Google Scholar 

  • Renfree MB, Papenfuss AT, Shaw G, Pask AJ (2009) Eggs, embryos and the evolution of imprinting: insights from the platypus genome. Reprod Fertil Dev 21:935–942

    Article  CAS  PubMed  Google Scholar 

  • Rogers JH (1985) Mouse histocompatibility-related genes are not conserved in other mammals. Embo J 4:749–753

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sambrook JG, Figueroa F, Beck S (2005) A genome wide survey of major histocompatibility complex (MHC) genes and their paralogues in zebrafish. BMC Genomics 6:152

    Article  PubMed Central  PubMed  Google Scholar 

  • Selwood L (2000) Marsupial egg and embryo coats. Cells Tissues Organs 166:208–219

    Article  CAS  PubMed  Google Scholar 

  • Shiina T, Shimizu S, Hosomichi K, Kohara S, Watanabe S, Hanzawa K, Beck S, Kulski JK, Inoko H (2004) Comparative genomic analysis of two avain (quail and chicken) MHC regions. J Immunol 172:6751–6763

    Article  CAS  PubMed  Google Scholar 

  • Siddle HV, Deakin JE, Baker ML, Miller RD, Belov K (2006) Isolation of major histocompatibility complex class I genes from the tammar wallaby (Macropus eugenii). Immunogenetics 58:487–493

    Article  CAS  PubMed  Google Scholar 

  • Siddle HV, Deakin JE, Coggill P, Hart E, Cheng Y, Wong ES, Harrow J, Beck S, Belov K (2009) MHC-linked and un-linked class I genes in the wallaby. BMC Genomics 10:310

    Article  PubMed Central  PubMed  Google Scholar 

  • Siddle HV, Marzec J, Cheng Y, Jones M, Belov K (2010) MHC gene copy number variation in Tasmanian devils: implications for the spread of a contagious cancer. Proc Biol Sci 277:2001–2006

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tallmadge RL, Lear TL, Antczak DF (2005) Genomic characterization of MHC class I genes of the horse. Immunogenetics 57:763–774

    Article  CAS  PubMed  Google Scholar 

  • Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance and maximum parsimony methods. Mol Biol Evol 28:2731–2739

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tyndale-Biscoe CH, Renfree MB (1987) Reproductive physiology of marsupials. Cambridge University Press, Cambridge

    Book  Google Scholar 

  • Warner CM, Gollnick SO, Flaherty L, Goldbard SB (1987) Analysis of Qa-2 antigen expression by preimplantation mouse embryos: possible relationship to the Ped gene product. Biol Reprod 36:611–616

    Article  CAS  PubMed  Google Scholar 

  • Yuhki N, Beck T, Stephens R, Neelam B, O’Brien SJ (2007) Comparative structure of human, dog, and cat MHC: HLA, DLA, and FLA. J Hered 98:390–399

    Article  CAS  PubMed  Google Scholar 

  • Zinkernagel RM, Doherty PC (1974) Immunological surveillance against altered self components by sensitised T lymphocytes in lymphocytic choriomeningitis. Nature 251:547–548

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Many thanks to Mrs. Jette Ziep and Ms Tanja Noventa for assistance in the laboratory and to Prof. Joerns Fickel for technical assistance with DNA sequencing. This project was funded by a PAKT grant from the Leibniz Gemeinschaft to BD, a Humboldt Postdoctoral Fellowship to BRM, an Australian Research Council Discovery Outstanding Research Award to MBR. Thank you to the Dahlem Research School for supporting this research with a travel grant to Mrs. Ina Buentjen.

Conflict of interest

The authors declare that they have no conflict of interest.

Authors’ contributions

BD, TBH, MBR and BRM designed the project. BRM and MBR collected and extracted the RNA from tammar wallaby placental tissues. IB isolated the sequences from tammar placenta and performed and checked PCR transcripts. SRF recapitulated all class I genes from published BAC libraries using bioinformatic resources and assisted with phylogenetic analysis and universal -UM primer design. All authors edited and approved the final manuscript.

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Authors and Affiliations

  1. Department of Reproduction Management, Leibniz Institute for Zoo and Wildlife Research, Alfred-Kowalke Strasse 17, Berlin, Germany

    Ina Buentjen, Barbara Drews & Thomas B. Hildebrandt

  2. School of BioSciences, The University of Melbourne, 3010, Victoria, Australia

    Stephen R. Frankenberg, Marilyn B. Renfree & Brandon R. Menzies

Authors
  1. Ina Buentjen
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  2. Barbara Drews
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  3. Stephen R. Frankenberg
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  4. Thomas B. Hildebrandt
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  5. Marilyn B. Renfree
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  6. Brandon R. Menzies
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Corresponding author

Correspondence to Brandon R. Menzies.

Electronic supplementary material

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Online Resource 1

Amino acid sequence comparison of tammar Maeu-UD like transcripts. Maeu-UD transcripts were present in placental tissue at days 18, 21 and 25 of pregnancy and were 99.87 % identical to the Maeu-UD gene (two nucleotide differences: yellow boxes). A single liver transcript also grouped with the Maeu-UD gene phylogenetically, but this sequence contained numerous nucleotide differences that encode 22 amino acid substitutions relative to Maeu-UD. The lack of variability in placental Maeu-UD transcripts from three different individuals suggests that the liver transcript is the product of an alternative gene. (PDF 246 kb)

Online Resource 2

Amino acid sequence comparison of marsupial MHC-I -UM genes. The MHC-I -UM gene is highly conserved in marsupials, sharing approximately 80 % amino acid identity between opossum, devil and wallaby. The α1 and α2 domains (underlined in red and blue, respectively) are particularly highly conserved and contain the protein-binding region that is normally highly polymorphic in classical MHC-I genes. The cysteine residue in the α1 domain (yellow box), identified as an unpaired cysteine in opossum, is also conserved in all marsupials. (PDF 150 kb)

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Buentjen, I., Drews, B., Frankenberg, S.R. et al. Characterisation of major histocompatibility complex class I genes at the fetal-maternal interface of marsupials. Immunogenetics 67, 385–393 (2015). https://doi.org/10.1007/s00251-015-0842-5

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  • DOI: https://doi.org/10.1007/s00251-015-0842-5

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