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Positional cloning of the allorecognition gene alr1 in the cnidarian Hydractinia symbiolongicarpus

par Rosa, Sabrina
Président du jury Pays, Etienne
Promoteur Leo, Oberdan
Publication Non publié, 2010-03-08

Thèse de doctorat

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Résumé :

Allorecognition, defined as the ability to discriminate between self and non-self, is ubiquitous to colonial metazoans and widespread in aclonal taxa. Invertebrate allorecognition phenomena are of broad interest and have long captured the attention of geneticists by virtue of the allotypic diversity they display, marine ecologists by virtue of their control of effector mechanisms determining the outcome of intraspecific competition, evolutionary biologists by virtue of their regulation of the level at which selection acts, and immunologists by virtue of their resemblance to the allogeneic interactions that characterize pregnancy and transplantation in vertebrates. Diverse histocompatibility modes have been described in the jawed vertebrates, protochordates, and cnidarians, which are to date the only three taxa for which a genetic model to study allorecognition has been developed. Outside of the MHC-based histocompatibility of vertebrates, allorecognition determinants have been recognized in only two invertebrates. In the tunicate Botryllus, two genes involved in the histocompatibility response were characterized, FuHc and fester. In Hydractinia, the loci controlling allorecognition, alr1 and alr2, were mapped to a single chromosomal region, the allorecognition complex, and alr2 was recently identified as a polymorphic immunoglobulin superfamily (IgSF) receptor. In this study, the identification of the second Hydractinia allodeterminant, alr1, was undertaken. Chapter I briefly reviews prominent allorecognition model organisms and details the phenomenon in the model organism, Hydractinia symbiolongicarpus studied here. Chapter II describes the isolation of a 300.8 kb alr1-containing chromosomal interval by positional cloning. The analysis of that interval for its gene content and the determination of a primary alr1 candidate, CDS4, are described in Chapter III. Chapter III also reveals the existence of a complex of IgSF-like genes, to which belongs CDS4. CDS4, a novel polymorphic IgSF receptor that encodes a type I transmembrane protein with two hypervariable immunoglobulin-like extracellular domains, was confirmed to be the alr1 allodeterminant in Chapter IV, based on the investigation of natural polymorphism. CDS4 allele sequences were found to largely predict the outcome of allorecognition responses within and between laboratory lines and wild-type colonies, confirming the identity of CDS4 as the classically defined locus alr1.