M and N blood group antigens are presented by glycophorins A (GPA) and B (GPB) of the erythrocyte membrane. GPA expresses M or N blood group antigen depending on the allelic gene (GPAM gene or GPAN gene), while GPB expresses only the N antigen. M or N blood group antigen is specified by the first and fifth NH2-terminal amino acid residues in the mature proteins, encoded by the second exon of these genes. Glycophorin E (GPE) gene, another member of this gene family, has a genomic structure very similar to that of GPB. However, a predicted product of GPE gene carries M blood group antigen. To delineate evolutionary events leading to the formation of the sequences for M or N blood group type determinant in the members of human glycophorin gene family, the nucleotide sequences of a 1.45-kilobase pair region including the 3' part of intron 1, exon 2, and the entire intron 2 were compared for GPAM, GPAN, GPB, and GPE genes. Encompassing exon 2, there were identical sequences stretches of 139 and 138 base pairs between GPAM and GPE genes and between GPAN and GPB genes, respectively. The data of the entire sequences in this region revealed that the divergence of the sequence between GPE and GPA genes (2.14-2.49%) is less than that of the sequence between GPE and GPB genes (3.10%). The higher rate of divergence in this region was observed between GPA and GPB genes (3.79-3.86%). These results strongly suggest that GPE gene acquired the sequence for M blood group type determinant from GPAM gene through gene conversion after duplication of a progenitor gene common to GPB and GPE genes.