Isolation of Xenopus LMP-7 homologues. Striking allelic diversity and linkage to MHC.

Abstract

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 presented by the MHC class I molecules. To elucidate the evolution of the LMP-7 gene at both the primary structure and genetic levels, we isolated LMP-7 cDNA clones from amphibian Xenopus laevis, which last shared a common ancestor with mammals 350 x 10(6) years ago. Two distinctive clones, showing an 85% predicted amino acid sequence identity with each other and 69 to 72% identity with human and mouse LMP-7, were identified 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 the 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 haplotypes among offspring of an f/f x f/g cross, and one recombinant revealed 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 coselection with particular class I alleles or by differential silencing of MHC genes in the polyploid X. laevis.