Clusters of point mutations are found exclusively around rearranged antibody variable genes.

作者: P. J. Gearhart , D. F. Bogenhagen

DOI: 10.1073/PNAS.80.11.3439

关键词: Pair-rule genePolar mutationChimeric genePoint mutationMutation rateGeneticsBiologyMolecular biologyGene clusterMutationGene conversion

摘要: Abstract We have examined the nucleotide sequences of a series murine antibody genes derived from one kappa light chain gene in order to gain insight into mechanism that specifically mutates variable genes. Six rearranged VK167 hybridoma and myeloma cells were cloned bacteriophage lambda libraries. The compared germ-line sequence gene, JK genes, CK identify sites mutation. Four six had extensive mutation which occurred exclusively 1-kilobase region DNA centered around V-J gene. No mutations found at more distant intervening or constant frequency was approximately 0.5% (32 per 6,749 base pairs). Mutations mostly due substitutions with no preference for transitions transversions. location each indicates they occur clusters random sites. observation downstream JK5 rules out models mutagenesis rely solely on conversion recombination. distribution high are most easily explained by error-prone repair occurs during several cycles cell division.

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