STRUCTURE OF THE MHC A-LOCUS AND B-LOCUS PROMOTERS IN HOMINOIDS - INSIGHTS ON THE EVOLUTION OF THE CLASS-I MHC MULTIGENE FAMILY

The expansion and contraction of mammalian class I multigene families raises the issue as to what determines the loss or retention of family members. We propose that accumulating changes in regulatory regions r esult in the loss of expression of the gene products during times crit ical to selection, leading to the extinction of misregulated genes. Th e structures of promoter regions of MHC class I genes in nonhuman prim ates support this view. The B promoters are more homogeneous and conta in regulatory elements also found in the promoters of the homologous c lass I genes of more distant mammals, whereas the A locus promoters we re significantly more heterogeneous, have fewer sequence motifs relate d to known transcription factor-binding sites and have accumulated nuc leotide substitutions within one of the widely conserved class I promo ter elements. These findings are consistent with the view that the mor e polymorphic B locus is the principal MHC locus encoding functional c lass I Ag-presenting molecules whereas the less polymorphic A locus is assuming a secondary role as a consequence of promoter defects.