CHROMOSOMAL LOCALIZATION OF THE PROTEASOME Z-SUBUNIT GENE REVEALS AN ANCIENT CHROMOSOMAL DUPLICATION INVOLVING THE MAJOR HISTOCOMPATIBILITYCOMPLEX

Proteasomes are the multi-subunit protease thought to play a key role in the generation of peptides presented by major histocompatibility co mplex (MHC) class I molecules. When cells are stimulated with interfer on gamma, two MHC-encoded subunits, low molecular mass poly-peptide (L MP) 2 and LMP7, and the MECL1 subunit encoded outside the MHC are inco rporated into the proteasomal complex, presumably by displacing the ho usekeeping subunits designated Y, X, and Z, respectively. These change s in the subunit composition appear to facilitate class I-mediated ant igen presentation, presumably bg altering the cleavage specificities o f the proteasome. Here we show that the mouse gene encoding the Z subu nit (Psmb7) maps to the paracentromeric region of chromosome 2, Inspec tion of the mouse loci adjacent to the Psmb7 locus provides evidence t hat the paracentromeric region of chromosome 2 and the MHC region on c hromosome 17 most likely arose as a result of a duplication that took place at an early stage of vertebrate evolution. The traces of this du plication are also evident in the homologous human chromosome regions (6p21.3 and 9q33-q34). These observations have implications in underst anding the genomic organization of the present-day MHC and offer insig hts into the origin of the MHC.