title: Mechanism and consequences of the duplication of the human C4/P450c21/gene X locus.
abstract: The adjacent C4 and P450c21 genes encode the fourth component of serum complement and steroid 21-hydroxylase respectively, and are tandemly duplicated in the human, murine, and bovine genomes. We recently cloned a cDNA for another duplicated gene, operationally termed X, which overlaps the 3' end of human P450c21 and has the opposite transcriptional orientation. Thus, the organization of the locus is 5'-C4A-21A-XA-C4B-21B-XB-3' (Y. Morel, J. Bristow, S. E. Gitelman, and W. L. Miller, Proc. Natl. Acad. Sci. USA 86:6582-6586, 1989). To determine how this locus was duplicated, we sequenced the DNA at the duplication boundaries and the 7 kb between P450c21A and C4B comprising the XA locus. The sequences located the duplication boundaries precisely and indicate that the duplication occurred by nonhomologous recombination. The boundaries are substantially different from those of the corresponding duplication in the mouse genome, suggesting that similar gene duplications may have occurred independently in ancestors of rodents and primates after mammalian speciation. Compared with XB, the XA gene is truncated at its 5' end and bears a 121-bp intragenic deletion causing a frameshift and premature translational stop signal. Nevertheless, XA is transcribed into a stable 2.6-kb polyadenylated RNA that is expressed uniquely in the adrenal gland.
authors.affiliation: Department of Pediatrics, University of California, San Francisco 94143.
authors.forename: S E
authors.initials: SE
authors.lastname: Gitelman
authors.forename: J
authors.initials: J
authors.lastname: Bristow
authors.forename: W L
authors.initials: WL
authors.lastname: Miller
mesh_terms: D000311:Adrenal Glands / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002645:Chickens; D002872:Chromosome Deletion; D003181:Complement C4 / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005333:Fetus; D005353:Fibronectins / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D009928:Organ Specificity; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D019063:Tenascin; D014158:Transcription, Genetic
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D003181:Complement C4; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D011506:Proteins; C074149:TNXA protein, human; D019063:Tenascin; D012313:RNA; D013255:Steroid 21-Hydroxylase