The Escherichia coli system of Cairns and Foster employs a lac frameshift mutation that reverts rarely (10^-9/cell/division) during unrestricted growth. However, when 10⁸ cells are plated on lactose medium, the nongrowing lawn produces ∼50 Lac⁺ revertant colonies that accumulate linearly with time over 5 days. Revertants carry very few associated mutations. This behavior has been attributed to an evolved mechanism ("adaptive mutation" or "stress-induced mutagenesis") that responds to starvation by preferentially creating mutations that improve growth. We describe an alternative model, "selective inbreeding," in which natural selection acts during intercellular transfer of the plasmid that carries the mutant lac allele and the dinB gene for an error-prone polymerase. Revertant genome sequences show that the plasmid is more intensely mutagenized than the chromosome. Revertants vary widely in their number of plasmid and chromosomal mutations. Plasmid mutations are distributed evenly, but chromosomal mutations are focused near the replication origin. Rare, heavily mutagenized, revertants have acquired a plasmid tra mutation that eliminates conjugation ability. These findings support the new model, in which revertants are initiated by rare pre-existing cells (10⁵) with many copies of the F'lac plasmid. These cells divide under selection, producing daughters that mate. Recombination between donor and recipient plasmids initiates rolling-circle plasmid over-replication, causing a mutagenic elevation of DinB level. A lac⁺ reversion event starts chromosome replication and mutagenesis by accumulated DinB. After reversion, plasmid transfer moves the revertant lac⁺ allele into an unmutagenized cell, and away from associated mutations. Thus, natural selection explains why mutagenesis appears stress-induced and directed.

中文翻译：

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选择性近亲繁殖：基因杂交驱动大肠杆菌凯恩斯-福斯特系统中明显的适应性突变。


凯恩斯和福斯特的大肠杆菌系统采用了lac移码突变，在不受限制的生长过程中很少恢复（10 ^-9 /细胞/分区）。然而，当 10 ^{8 个}细胞铺在乳糖培养基上时，非生长草坪会产生约 50 个 Lac ⁺回复体菌落，这些菌落在 5 天内随时间线性累积。回复突变体携带很少的相关突变。这种行为归因于一种进化机制（“适应性突变”或“应激诱导突变”），该机制通过优先产生促进生长的突变来应对饥饿。我们描述了另一种模型，“选择性近交”，其中自然选择在携带突变lac等位基因和易错聚合酶的dinB基因的质粒的细胞间转移过程中起作用。回复体基因组序列表明，质粒比染色体受到更强烈的诱变。回复突变体的质粒和染色体突变数量差异很大。质粒突变分布均匀，但染色体突变集中在复制起点附近。罕见的、经过严重诱变的回复突变体已经获得了质粒tra突变，从而消除了接合能力。这些发现支持了新模型，其中回复体是由具有许多 F' lac质粒拷贝的稀有预先存在的细胞 (10 ⁵ ) 启动的。这些细胞在选择下分裂，产生交配的子细胞。供体和受体质粒之间的重组启动滚环质粒过度复制，导致 DinB 水平诱变升高。 lac ⁺回复事件通过积累的 DinB 启动染色体复制和诱变。回复后，质粒转移将回复的lac ⁺等位基因转移到未诱变的细胞中，并远离相关突变。因此，自然选择解释了为什么诱变似乎是由应激诱导和定向的。