title: Sequence diversification and exon inactivation in the glycophorin A gene family from chimpanzee to human.
abstract: In humans, the allelic diversity of MNSs glycophorins (GP) occurs mainly through the recombinational modulation of silent exons (pseudoexons) in duplicated genes. To address the origin of such a mechanism, structures of GPA, GPB, and GPE were determined in chimpanzee, the only higher primate known to have achieved a three-gene framework as in humans. Pairwise comparison of the chimpanzee and human genes revealed a high degree of sequence identity and similar exon-intron organization. However, the chimpanzee GPA gene lacks a completely formed M- or N-defining sequence as well as a consensus sequence for the Asn-linked glycosylation. In the case of the GPB gene, exon III is expressed in the chimpanzee but silenced, as a pseudoexon, in the human. Therefore, the protein product in the chimpanzee bears a larger extracellular domain than in the human. For the GPE genes, exon III and exon IV have been inactivated by identical donor splice-site mutations in the two species. Nevertheless, the chimpanzee GPE-like mRNA appeared to be transcribed from a GPB/E composite gene containing no 24-bp insertion sequence in exon V for the transmembrane domain. These results suggest a divergent processing of exonic units from chimpanzee to human in which the inactivation of GPB exon III preserved a limited sequence repertoire for diversification of human glycophorins.
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, NY 10021, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Huang
authors.forename: S S
authors.initials: SS
authors.lastname: Xie
authors.forename: W
authors.initials: W
authors.lastname: Socha
authors.forename: O O
authors.initials: OO
authors.lastname: Blumenfeld
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D017931:DNA Primers; D015342:DNA Probes; D018076:DNA, Complementary; D005091:Exons; D014644:Genetic Variation; D006021:Glycophorins / Q000235:genetics*; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D002679:Pan troglodytes / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D017931:DNA Primers; D015342:DNA Probes; D018076:DNA, Complementary; D006021:Glycophorins; D004247:DNA