Mutations in budding yeast occur in meiosis at higher frequencies than in cells grown vegetatively. In contrast to mutations that occur in somatic cells, meiotic mutations have a special, long-range impact on evolution, because they are transferred to the following generations through the gametes. Understanding the mechanistic basis of meiotic mutagenicity is still lacking, however. Here, we report studies of mutagenicity in the reporter gene CAN1, in which forward mutation events in meiosis are sevenfold higher than in mitotic cells, as determined by fluctuation analysis. Meiotic mutations appear approximately at the same time as heteroallelic-recombination products and as meiotic DSBs. Recombination-associated timing of meiotic mutagenicity is further augmented by the absence of meiotic mutations in cells arrested after pre-meiotic DNA synthesis. More than 40% of the mutations generated in meiosis in CAN1 are found on chromosomes that have recombined in the 2.2 kb covering the reporter, implying that the mutations have resulted from recombination events and that meiotic recombination is mutagenic. The induced expression in yeast meiosis of low-fidelity DNA polymerases coded by the genes REV1, REV3, RAD30, and POL4 makes them attractive candidates for introducing mutations. However, in our extensive experiments with polymerase-deleted strains, these polymerases do not appear to be the major source of meiotic mutagenicity. From the connection between meiotic mutagenicity and recombination, one may conclude that meiotic recombination has another diversification role, of introducing new mutations at the DNA sequence level, in addition to reshuffling of existing variation. The new, rare meiotic mutations may contribute to long-range evolutionary processes and enhance adaptation to challenging environments.

中文翻译：

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酵母减数分裂期间新突变出现的时间及其与重组的关系。

减数分裂中发芽酵母中的突变发生的频率高于无性生长中的细胞。与体细胞中发生的突变相反，减数分裂突变对进化有特殊的长期影响，因为减数分裂突变通过配子转移到了后代。但是，仍然缺乏对减数分裂诱变机理的了解。在这里，我们报道了报告基因CAN1中的致突变性研究，其中减数分裂中的正向突变事件比有丝分裂细胞高7倍。减数分裂突变与异源等位基因重组产物和减数分裂DSB几乎同时出现。与减数分裂致突变性的重组相关的时机由于在减数分裂前DNA合成后被捕的细胞中不存在减数分裂突变而进一步增加。在CAN1减数分裂中产生的突变中，有超过40％的突变是在覆盖报道基因的2.2 kb染色体上发现的，这表明该突变是由重组事件引起的，并且减数分裂重组是诱变的。REV1，REV3，RAD30和POL4基因编码的低保真DNA聚合酶在酵母减数分裂中的诱导表达使其成为引入突变的诱人候选物。但是，在我们对缺失聚合酶的菌株进行的广泛实验中，这些聚合酶似乎不是减数分裂诱变的主要来源。从减数分裂诱变性和重组之间的联系，可以得出结论，减数分裂重组除了改变现有变异之外，还具有另一种多样化的作用，即在DNA序列水平上引入新的突变。新的，