ALU ELEMENTS OF THE PRIMATE MAJOR HISTOCOMPATIBILITY COMPLEX

The chromosomal region constituting the major histocompatibility compl ex (MHC) has undergone complex evolution that is often difficult to de cipher. An important aid in the elucidation of the MHC evolution is th e presence of Alu elements (repeats) which serve as markers for tracin g chromosomal rearrangements. As the first step toward the establishme nt of sets of evolutionary markers for the MHC, Alu elements present i n selected MHC haplotypes of the human species, the gorilla, and the c himpanzee were identified. Restriction fragments of cosmid clones from the libraries of the three species were hybridized with Alu-specific probes, Alu elements were amplified by the polymerase chain reaction, and the amplification products were sequenced. In some cases, sequence s of the regions flanking the Alu elements were also obtained. Altoget her, 31 new Alu elements were identified, representing six Alu subfami lies. The average density of Alu elements in the MHC is one element pe r four kilobases (kb) of sequence. Alu elements have apparently been i nserted steadily into the MHC over the last 65 million years (my). On average, one Alu element is inserted into the primate MHC every 4 my. Analysis of the human DR3 haplotype supports its origin by duplication from an ancestral haplotype consisting of DRB1 and DRB2 genes. The sh aring of an old Alu element by the DRB1 and DRB2 genes, in turn, suppo rts their divergence from a common ancestor more than 55 my ago.