Detailed physical mapping of the genes encoding glycophorins A, B and E, as revealed by P1 plasmids containing human genomic DNA.

Human glycophorins A, B and E (GPA, GPB and GPE) are members of the glycophorin gene family encompassing a 330-kb genomic segment located on chromosome 4, band q31 [Onda et al., J. Biol. Chem., 269 (1994) 13013-13020]. This gene family was apparently generated by two successive duplications of an ancestral gene. One of the progenitor genes, resulting from the first duplication, directly evolved into the GPA gene. The other progenitor gene acquired a unique 3'-region sequence and was then duplicated to yield GPB and GPE. In order to obtain a more detailed understanding of how these different members of the gene family evolved, we isolated several P1 plasmid clones encoding GPA, GPB or GPE. The precise locations of exon 1 and the exon encoding the transmembrane (TM) domain in GPA, GPB and GPE were then determined by hybridization with specific probes after restricted DNA fragments were separated by pulsed-field gel electrophoresis. The results obtained showed that the distances between exon 1 and exon 2 are almost equal for GPA and GPB, whereas this distance is larger in GPE. In contrast, the distance between exon 2 and the exon encoding the TM domain was shown to be the same among GPA, GPB and GPE. These results suggest that the gene divergence, i.e., insertions or deletions, took place after two successive duplications and supports the hypothesis that GPE acquired a portion of the GPA sequence surrounding exon 2 by gene conversion.