EVOLUTIONARY STUDY OF MULTIGENIC FAMILIES MAPPING CLOSE TO THE HUMAN MHC CLASS-I REGION

During a search for novel coding sequences within the human MHC class I region (chromosome 6p21.3), we found an exon (named B30-2) coding fo r a 166-amino-acid peptide which is very similar to the C-terminal dom ain of several coding sequences: human 52-kD Sjogren's syndrome nuclea r antigen A/Ro (SS-A/Ro) and ret finger protein (RFP), Xenopus nuclear factor 7 (XNF7), and bovine butyrophilin. The first three of these pr oteins share similarities over the whole length of the molecule wherea s butyrophilin is similar in the C-terminal domain. The N-terminal dom ain of butyrophilin is similar to rat myelin/oligodendrocyte glycoprot ein (MOG) and chicken B blood group system (B-G) protein. These domain s are components of a new subfamily of the immunoglobulin superfamily (IgSF). Butyrophilin is thus a mosaic protein composed of the MOG/B-G Ig-like domain and the C-terminal domain of 52-kD SS-A/Ro, RFP, and XN F7 (B30-2-1ike domain). Moreover, in situ hybridization shows that RFP , butyrophilin, and MOG map to the human chromosome 6p21.3-6p22 region and are thus close to the MHC class I genes. It is therefore possible that the butyrophilin gene is the product of an exon shuffling event which occurred between ancestors of the RFP and MOG genes. To our know ledge, this is the first example of the colocalization of a chimeric g ene and its putative progenitors. Finally, regulatory protein T-lympho cyte 1 (Rpt-1) shares similarities with the N-terminal halves of RFP, 52-kD SS-A/Ro, and XNF7, but not with the B30-2-1ike domain. We show t hat the ancestral Rpt-1 gene evolved by overprinting.