The candidate Fu/HC gene in Botryllus schlosseri (Urochordata) and ascidians' historecognition - An oxymoron?

Allorecognition, distinguishing self from non-self allogeneic tissues is the underlying basis of innate immunity. In the colonial tunicate Botryllus schlosseri this historecognition is governed at a single genetic locus, Fu/HC (for fusibility/histocompatibility), with hundreds of co-dominantly expressed alleles. Several years ago, De Tomaso et al. (2005) have revolutionized the discipline of invertebrate allorecognition by describing a novel form of immune recognition in B. schlosseri, a non-vertebrate candidate histocompatibility gene (cFu/HC), revealing that allorecognition machinery in urochordates has nothing in common with the vertebrates' MHC-based histocompatibility. The authors reported absolute concordance of fusibility and cFu/HC genotype, predicted fusion/rejection outcomes in allorecognition settings from allelic polymorphism at the cFu/HC, also claiming cFu/HC gene expressions only in tissues directly engaged in histocompatibility. Here, we raise queries for the validity of the results and conclusions of De Tomaso et al. (2005) publication. Our reservations include discrepancies in the paper's results, including the perplexing absence of key sequencing material from public domains and above all, our own impugning outcomes. These include cloning efforts, in situ hybridization results, semi quantitative PCR outcomes, and the incongruence emerged between fusion/rejection profiles and cFu/HC segregated polymorphism that separately and cumulatively contradict the original publication. We conclude that Botryllus histocompatibility properties are not signaled in the claimed cFu/HC and that cFu/HC gene is unlikely the allodeterminant for Botryllus histocompatibility locus. Hence, the molecular nature of the Fu/HC locus in botryllid ascidians is still awaiting elucidation.