ORGANIZATION OF THE HUMAN RH50A GENE (RHAG) AND EVOLUTION OF BASE COMPOSITION OF THE RH GENE FAMILY

Human Rh (rhesus) antigens are expressed in the red cell membrane as a multi-subunit complex, the central core of which is presumably compos ed of a tetramer made of two Rh and two Rh50 protein subunits. The int eraction between Rh and Rh50 polypeptides is thought to be crucial to the correct assembly and transport of the complex to the cell surface. Here, we show that the human RH50A gene (RHAG) is composed of 10 exon s whose size and exon/intron junctions are well conserved compared to those of the RR genes. We have also analyzed the RH50A 5' flanking reg ion where the transcription initiation site has been identified. These results conclusively establish that the RH50A and RH genes do belong to the same gene family. Moreover, we show that the RH50A and RH genes are embedded in different compositional genomic contexts (i.e., diffe rent isochores) that are likely to drive the evolution of these genes, the base compositions (G+C content) of which differ drastically. Fina lly, we propose a scenario in which an RH50-like gene is likely to hav e played a founding role in the evolution of the RH gene family. (C) 1 998 Academic Press.