CLUSTERING OF DIVERSE REPLICATED SEQUENCES IN THE MHC - EVIDENCE FOR EN-BLOC DUPLICATION

The MHC contains clusters of polymorphic duplicated genes and gene seq uences. It has been thought that these duplicated genes and sequences have arisen from single gene duplications. We compared the cloned regi on between TNF and HLA-B with the region in close proximity to HLA-A u sing sequence analysis and DNA hybridization. The results indicate tha t several sequences existing in the region centromeric of HLA-B are al so present in close proximity to HLA-A. These include sequences belong ing to the P5, BAT1, and PERB11 gene families as well as HLA class I g ene sequences. Interestingly, when the two regions of approximately 20 0 kilobases are compared, the replicated sequences are organized simil arly but in an inverted fashion suggesting the existence of an histori cal inverted en bloc duplication. Thus, we propose that the origin of these MHC gene clusters involves several mechanisms. In addition to si ngle gene replication, a long-range duplication of a genomic block mus t have occurred. It is possible that a block at the telomeric end of t he MHC represents a basic functional genomic unit conserved and duplic ated en bloc.