Although the ability to distinguish between self and non-self (that is, histocompatibility) is common among metazoans, the genetic basis of this process has only been well described for vertebrates. In vertebrates, this process is mediated by molecules that are encoded by the highly polymorphic MHC locus and results in the rejection of transplants from donors who do not carry identical MHC alleles. Now, a report in Nature describes the isolation and characterization of the first known invertebrate histocompatibility gene.

When colonies of the sea squirt Botryllus schlosseri come into contact, they either fuse into a single colony or reject fusion. This was previously shown to be determined by histocompatibility reactions occurring at the periphery of each colony, the outcome of which depends on the alleles of the highly polymorphic locus FuHC (fusibility/histocompatibility) present in each colony. In this study, the authors mapped the FuHC locus and identified a candidate gene (cFuHC) that is highly polymorphic and encodes an immunoglobulin-superfamily member with no marked homology with MHC molecules. Polymorphisms in cFuHC were shown to segregate with histocompatibility, as determined by fusion or rejection of pairs of colonies. Protein expression was also shown at sites of histocompatibility reactions.

Histocompatibility in vertebrates is thought to be a by-product of MHC-gene polymorphism. For B. schlosseri, however, histocompatibility reactions might restrict DNA exchange, allowing these organisms to maintain a diverse gene pool. So, this form of interaction might have preserved the genetic fitness of our ancestors. The dual function of MHC molecules in histocompatibility and immunity has long indicated that these processes are evolutionarily linked, and FuHC is the first structural link between vertebrate adaptive immunity and invertebrate histocompatibility.