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Isolation and characterization of a protochordate histocompatibility locus


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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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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Correspondence to Anthony W. De Tomaso.

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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 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).

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