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Isolation and characterization of a protochordate histocompatibility locus

Nature volume 438, pages 454–459 (2005)Cite this article

Abstract

Histocompatibility—the ability of an organism to distinguish its own cells and tissue from those of another—is a universal phenomenon in the Metazoa. In vertebrates, histocompatibility is a function of the immune system controlled by a highly polymorphic major histocompatibility complex (MHC), which encodes proteins that target foreign molecules for immune cell recognition. The association of the MHC and immune function suggests an evolutionary relationship between metazoan histocompatibility and the origins of vertebrate immunity. However, the MHC of vertebrates is the only functionally characterized histocompatibility system; the mechanisms underlying this process in non-vertebrates are unknown. A primitive chordate, the ascidian Botryllus schlosseri, also undergoes a histocompatibility reaction controlled by a highly polymorphic locus. Here we describe the isolation of a candidate gene encoding an immunoglobulin superfamily member that, by itself, predicts the outcome of histocompatibility reactions. This is the first non-vertebrate histocompatibility gene described, and may provide insights into the evolution of vertebrate adaptive immunity.

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Figure 1: Histocompatibility and positional cloning of the FuHC locus in Botryllus schlosseri.
Figure 2: Graphic representation of the overall polymorphism of the cFuHC.
Figure 3: Expression analysis of the cFuHC.

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References

  1. Flajnik, M. F., Miller, K. & Dupasquier, L. in Fundamental Immunology 5th edn (ed. Paul, W. E.) 519–570 (Lippincott, Williams and Wilkins, Philadelphia, 2003)

    Google Scholar 

  2. Dupasquier, L., Zucchetti, I. & De Santis, R. Immunoglobulin superfamily receptors in protochordates: before RAG time. Immunol. Rev. 198, 233–248 (2004)

    Article  CAS  Google Scholar 

  3. Oka, H. & Watanabe, H. Problems of colony specificity in compound ascidians. Bull. Mar. Biol. Stn Asamushi 10, 153–155 (1960)

    Google Scholar 

  4. Sabbadin, A. Le basi genetiche dell capacita di fusione fra colonie in Botryllus schlosseri (Ascidiacea). Atti Accad. Naz. Lincei Rend. 32, 1031–1035 (1962)

    Google Scholar 

  5. Scofield, V. L., Schlumpberger, J. M., West, L. A. & Weissman, I. L. Protochordate allorecognition is controlled by an MHC-like gene system. Nature 295, 499–502 (1982)

    Article  ADS  CAS  Google Scholar 

  6. Boyd, H. C., Brown, S. K., Harp, J. A. & Weissman, I. L. Growth and sexual maturation of laboratory-cultured Monterey Botryllus schlosseri. Biol. Bull. 170, 91–109 (1986)

    Article  Google Scholar 

  7. De Tomaso, A. W., Saito, Y., Ishizuka, K. J., Palmeri, K. J. & Weissman, I. L. Mapping the genome of a model protochordate. I. A low resolution genetic map encompassing the fusion/histocompatibility (Fu/HC) locus of Botryllus schlosseri. Genetics 149, 277–287 (1998)

    CAS  PubMed  PubMed Central  Google Scholar 

  8. De Tomaso, A. W. & Weissman, I. L. Initial characterization of a protochordate histocompatibility locus. Immunogenetics 55, 480–490 (2003)

    Article  CAS  Google Scholar 

  9. Burge, C. B. & Karlin, S. Finding the genes in genomic DNA. Curr. Opin. Struct. Biol. 8, 346–354 (1998)

    Article  CAS  Google Scholar 

  10. Williams, A. F. & Barclay, A. N. The immunoglobulin superfamily—domains for surface recognition. Annu. Rev. Immunol. 6, 381–405 (1988)

    Article  CAS  Google Scholar 

  11. Grosberg, R. K. & Hart, M. W. Mate selection and the evolution of highly polymorphic self/non-self recognition genes. Science 289, 2111–2114 (2000)

    Article  ADS  CAS  Google Scholar 

  12. De Tomaso, A. W. & Weissman, I. L. Evolution of a protochordate allorecognition locus. Science 303, 977 (2004)

    Article  CAS  Google Scholar 

  13. Burnet, F. M. Self-recognition in colonial marine forms and flowering plants in relation to the evolution of immunity. Nature 232, 123–126 (1971)

    Article  ADS  Google Scholar 

  14. Cannon, J. P., Haire, R. N., Rast, J. P. & Litman, G. W. The phylogenetic origins of the antigen-binding receptors and somatic diversification mechanisms. Immunol. Rev. 200, 200–212 (2004)

    Article  Google Scholar 

  15. Kärre, K., Ljunggren, H. G., Piontek, G. & Kiessling, R. Selective rejection of H–2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 319, 675–678 (1986)

    Article  ADS  Google Scholar 

  16. Azumi, K. et al. Genomic analysis of immunity in a basal chordate and evolution of the vertebrate immune system: waiting for Godot. Immunogenetics 55, 570–581 (2003)

    Article  CAS  Google Scholar 

  17. Izzard, C. S. Migration of germ cells through successive generations of pallial buds in Botryllus schlosseri. Biol. Bull. 135, 424–431 (1968)

    Google Scholar 

  18. Sabbadin, A. & Zaniolo, G. Sexual differentiation and germ cell transfer in the colonial ascidian Botryllus schlosseri. J. Exp. Zool. 207, 279–301 (1979)

    Article  Google Scholar 

  19. Stoner, D. S., Rinkevich, B. & Weissman, I. L. Heritable germ and somatic cell lineage competitions in chimeric colonial protochordates. Proc. Natl Acad. Sci. USA 96, 9148–9153 (1999)

    Article  ADS  CAS  Google Scholar 

  20. Buss, L. W. Somatic cell parasitism and the evolution of somatic tissue. Proc. Natl Acad. Sci. USA 79, 5337–5341 (1982)

    Article  ADS  CAS  Google Scholar 

  21. Buss, L. W. The Evolution of Individuality (Princeton Univ. Press, New Jersey, 1987)

    Google Scholar 

  22. Owen, R. D. Immunologic consequence of vascular anastomoses between twins. Science 210, 400–401 (1945)

    Article  ADS  Google Scholar 

  23. Mintz, B. & Russel, E. S. Gene-induced embryological modifications of primordial germ cells in the mouse. J. Exp. Zool. 134, 207–237 (1957)

    Article  CAS  Google Scholar 

  24. Carlyle, J. R. et al. Missing self-recognition of Ocil/Clr-b by inhibitory NKR-P1 natural killer cell receptors. Proc. Natl Acad. Sci. USA 101, 3527–3532 (2004)

    Article  ADS  CAS  Google Scholar 

  25. Iizuka, K., Naidenko, O. V., Plougastel, B. F., Fremont, D. H. & Yokoyama, W. M. Genetically linked C-type lectin-related ligands for the NKRP1 family of natural killer cell receptors. Nature Immunol. 4, 801–807 (2003)

    Article  CAS  Google Scholar 

  26. Bottino, C. et al. Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J. Exp. Med. 198, 557–567 (2003)

    Article  CAS  Google Scholar 

  27. Altschul, S. F. et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402 (1997)

    Article  CAS  Google Scholar 

  28. Tusnády, G. E. & Simon, I. Principles governing amino acid composition of integral membrane proteins: applications to topology prediction. J. Mol. Biol. 283, 489–506 (1998)

    Article  Google Scholar 

  29. Puntervoll, P. et al. ELM server: a new resource for investigating short functional sites in modular eukaryotic proteins. Nucleic Acids Res. 31, 3625–3630 (2003)

    Article  CAS  Google Scholar 

  30. Frohman, M. A., Dush, M. K. & Martin, G. R. Rapid production of full-length cDNAs from rare transcripts; amplification using a single gene-specific oligonucleotide primer. Proc. Natl Acad. Sci. USA 85, 8998–9002 (1987)

    Article  ADS  Google Scholar 

  31. Pearson, W. R. & Lipman, D. J. Improved tools for biological sequence comparison. Proc. Natl Acad. Sci. USA 85, 2444–2448 (1988)

    Article  ADS  CAS  Google Scholar 

  32. Davidson, B. & Swalla, B. J. A molecular analysis of ascidian metamorphosis reveals activation of an innate immune response. Development 129, 4739–4751 (2002)

    Article  CAS  Google Scholar 

  33. Bassham, S. & Postlethwait, J. Brachyury (T) expression in embryos of a larvacean urochordate, Oikopleura dioica, and the ancestral role of T. Dev. Biol. 220, 322–332 (2000)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank C. Amemiya, D. Rokhsar, R. Davis, A. Southwick, M. Miranda, D. Ransom, J. Cannon, G. Litman, R. Haire, A. Voskoboynik, J. Wallace and E. Johnson. This study was supported by grants from the National Institutes of Health (a Trans-BAC Sequencing grant) and the Community Sequencing Program at the Department of Energy Joint Genome Institute.

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Authors and Affiliations

  1. Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, California, 94305

    Anthony W. De Tomaso, Spencer V. Nyholm, Karla J. Palmeri, Katherine J. Ishizuka, William B. Ludington, Katrina Mitchel & Irving L. Weissman

  2. Department of Biology, Hopkins Marine Station, California, 93950, Pacific Grove, USA

    Anthony W. De Tomaso, Spencer V. Nyholm, Karla J. Palmeri, Katherine J. Ishizuka, William B. Ludington, Katrina Mitchel & Irving L. Weissman

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  1. Anthony W. De Tomaso
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Correspondence to Anthony W. De Tomaso.

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Competing interests

Sequence information has been deposited at the NCBI with the accession numbers DQ160291 (for the membrane-bound form) and DQ160292 (for the secreted form). Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Supplementary information

Supplementary Figure 1

Amino acid sequence of the FuHC A allele. (PPT 28 kb)

Supplementary Figure Legend

Text to accompany the above Supplementary Figure. (DOC 20 kb)

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De Tomaso, A., Nyholm, S., Palmeri, K. et al. Isolation and characterization of a protochordate histocompatibility locus. Nature 438, 454–459 (2005). https://doi.org/10.1038/nature04150

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