ISOLATION OF XENOPUS LMP-7 HOMOLOGS - STRIKING ALLELIC DIVERSITY AND LINKAGE TO MHC

The mammalian low molecular mass protein-7 (LMP-7) gene resides in the class II region of the MHC, and its product is most probably involved , as a component of a proteasome, in the processing of Ags to be prese nted by the MHC class I molecules. To elucidate the evolution of the L MP-7 gene at both the primary structure and genetic levels, we isolate d LMP-7 cDNA clones from amphibian Xenopus laevis, which last shared a common ancestor with mammals 350 x 10(6) years ago. Two distinctive c lones, showing an 85% predicted amino acid sequence identity with each other and 69 to 72% identity with human and mouse LMP-7, were identif ied from a liver cDNA library of outbred frogs and named XeLMP-7A and XeLMP-7B. XeLMP-7A- and XeLMP-7B-specific probes were used to detect t he corresponding genes by using partially inbred frogs with known MHC haplotypes. DNA of the g and j haplotypes hybridized with the XeLMP-7A probe, whereas the f and r haplotype DNA hybridized with the XeLMP-7B probe. These hybridization patterns cosegregated with the MHC haploty pes among offspring of an f/f x f/g cross, and one recombinant reveale d that the LMP-7 gene is linked more closely to class II than to class I or class III genes. Taken together, the data indicate that XeLMP-7A and XeLMP-7B are highly diverse alleles at a single locus in the frog MHC. The great allelic diversity can be explained either by coselecti on with particular class I alleles or by differential silencing of MHC genes in the polyploid X. laevis.