High-Frequency Genetic Reversion Mediated by a DNA Duplication: The Mouse Pink-Eyed Unstable Mutation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 1; pp. 297 - 301
• Main Authors: Gondo, Yoichi, Gardner, John M., Nakatsu, Yoshimichi, Durham-Pierre, Donna, Deveau, Susan A., Kuper, Cynthia, Brilliant, Murray H.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.01.1993; National Acad Sciences; National Academy of Sciences
• Subjects: Alleles; Animals; Base Sequence; Biological and medical sciences; Blotting, Southern; Classical genetics, quantitative genetics, hybrids; Cloning, Molecular; Crossing Over, Genetic; Deoxyribonucleic acid; DNA; DNA - genetics; DNA - isolation & purification; DNA probes; DNA Replication; Fundamental and applied biological sciences. Psychology; Gels; Genetic loci; Genetic mutation; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genome; Genomic Library; Genomics; Genotype; Homozygote; Mice; Mice, Inbred C57BL; Mice, Mutant Strains - genetics; Molecular Sequence Data; Molecular Weight; Multigene Family; Mutation; Nucleotides; Oligodeoxyribonucleotides; Polymerase Chain Reaction; Puns; Restriction Mapping; Rodents; Sequence Homology, Nucleic Acid; Spleen - physiology; Vertebrata; Vertebrata; Recombination; Reversion; Mammalia; Mouse; Rodentia; Restriction map; Chromosome DNA; Instability; Gene duplication; Molecular cloning; Tandemly repeated sequence
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.1.297

The mouse pink-eyed unstable (pun) mutation, affecting coat color, exhibits one of the highest reported reversion frequencies of any mammalian mutation and is associated with a duplication of genomic DNA at the p locus. In this study, genomic clones containing the boundaries of the punduplication were isolated and characterized. The structure of these sequences and their wild-type and revertant counterparts were analyzed by restriction mapping, PCR product analysis, DNA sequence analysis, and pulsed-field gel electrophoresis. DNA from punwas distinguished from wild-type and revertant DNA by a head-to-tail tandem duplication of ≈ 70 kilobases. No differences were detected between revertant and wild-type DNAs. Thus, the reversion in phenotype of punmice is coupled with the loss of one copy of an ≈ 70-kilobase duplicated segment. Testable models are presented to account for punreversion