Schaaper R M, Danforth B N, Glickman B W
J Mol Biol. 1986 May 20;189(2):273-84. doi: 10.1016/0022-2836(86)90509-7.
We have obtained via DNA sequence analysis a spectrum of 174 spontaneous mutations occurring in the lac I gene of Escherichia coli. The spectrum comprised base substitution, frameshift, deletion, duplication and insertion mutations, of which the relative contributions to spontaneous mutation could be estimated. Two thirds of all lacI mutations occurred in the frameshift hotspot site. An analysis of the local DNA sequence suggested that the intensity of this hotspot may depend on structural features of the DNA that extend beyond those permitted by the repeated tetramer at this site. Deletions comprised the largest non-hotspot class (37%). They could be divided into two subclasses, depending on whether they included the lac operator sequence; the latter was found to be a preferred site for deletion endpoints. Most of the deletions internal to the lacI gene were associated with the presence of directly or invertedly repeated sequences capable of accounting for their endpoints. Base substitutions comprised 34% of the non-hotspot events. Unlike the base substitution spectrum obtained via nonsense mutations, G . C----A . T transitions do not predominate. A new base substitution hotspot was discovered at position +6 in the lac operator; its intensity may reflect specific features of the operator DNA. IS1 insertion mutations contributed 12% of the non-hotspot mutations and occurred dispersed throughout the gene in both orientations. Since the lacI gene is not A + T-rich, the contribution of IS1 insertion to spontaneous mutation in general might be underestimated. Single-base frameshift mutations were found only infrequently. In general, they did not occur in runs of a common base. Instead, their occurrence seemed based on the "perfection" of direct or inverted repeats in the local DNA sequence. Three (tandem) duplication events were recovered. No repeated sequences were found that might have determined their endpoints.
我们通过DNA序列分析获得了大肠杆菌lacI基因中发生的174种自发突变的谱图。该谱图包括碱基替换、移码、缺失、重复和插入突变，其中对自发突变的相对贡献可以估算。所有lacI突变的三分之二发生在移码热点位点。对局部DNA序列的分析表明，该热点的强度可能取决于DNA的结构特征，这些特征超出了该位点重复四聚体所允许的范围。缺失构成了最大的非热点类别（37%）。它们可分为两个亚类，这取决于它们是否包含lac操纵序列；发现后者是缺失终点的首选位点。lacI基因内部的大多数缺失与能够解释其终点的正向或反向重复序列的存在有关。碱基替换占非热点事件的34%。与通过无义突变获得的碱基替换谱不同，G.C→A.T转换并不占主导。在lac操纵子的+6位置发现了一个新的碱基替换热点；其强度可能反映了操纵子DNA的特定特征。IS1插入突变占非热点突变的12%，并且以两种方向分散在整个基因中。由于lacI基因并非富含A+T，一般来说IS1插入对自发突变的贡献可能被低估。单碱基移码突变很少被发现。一般来说，它们不会出现在同一碱基的连续排列中。相反，它们的出现似乎基于局部DNA序列中正向或反向重复的“完美性”。我们发现了三个（串联）重复事件。没有发现可能决定其终点的重复序列。
