Insight into the primordial MHC from studies in ectothermic vertebrates

MHC classical class I and class II genes have been identified in representa tive species from all major jawed vertebrate taxa, the oldest group being t he cartilaginous fish, whereas no class I/II genes of any type have been de tected in animals from older taxa. Among ectothermic vertebrate classes, st udies of MHC architecture have been done in cartilaginous fish (sharks), bo ny fish (several teleost species), and amphibians (the frog Xenopus). The X enopus MHC contains class I, class II, and class III genes, demonstrating t hat all of these genes were linked in the ancestor of the tetrapods, but th e gene order is not the same as that in mouse/man. Studies of polyploid Xen opus suggest that MHC genes can be differentially silenced when multiple co pies are present; i.e. MHC 'subregions' can be silenced. Surprisingly, in a ll teleosts examined to date class I and class II genes are not linked. Lik ewise, class III genes like the complement genes factor B (Bf) and C4 are s cattered throughout the genome of teleosts. However, the presumed classical class I genes are closely linked to the 'immune' proteasome genes, LMP2 an d LMP7, and to the peptide-transporter genes (TAP), implying that a true 'c lass I region' exists in this group. A similar type of linkage group is fou nd in chickens and perhaps Xenopus, and thus it may reveal the ancestral or ganization of class I-associated genes. In cartilaginous fish, classical an d non-classical class I genes have been isolated from three shark species, and class II A and B chain genes from nurse sharks. Studies of MHC Linkage in sharks are being carried out to provide further understanding of the put ative primordial organization of MHC. Segregation studies in one shark fami ly point to linkage of classical class I and class II genes, suggesting tha t the non-linkage of these genes in teleosts is a derived characteristic.