Rate and molecular spectrum of spontaneous mutations in the bacterium Escherichia coli as determined by whole-genome sequencing

Rate and molecular spectrum of spontaneous mutations in the bacterium Escherichia coli as determined by whole-genome sequencing
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DOI:
10.1073/pnas.1210309109
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发表时间:
2012-10-09
影响因子:
11.1
通讯作者:
Foster, Patricia L.
Foster, Patricia L.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lee, Heewook;Popodi, Ellen;Foster, Patricia L.

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对自发突变的速度和性质的了解是理解进化和分子过程的基础。在这份报告中,我们分析了野生型大肠杆菌及其衍生的错配修复缺陷(MMR)在数千代中积累的自发突变,错配修复是纠正复制错误的主要途径。主要结论是:(I)野生型菌株的突变率与每代基因组1×10(-3)的突变率相似;(Ii)野生型菌株的突变具有预期的G:C>A:T突变偏向,但在没有MMR的情况下,突变偏向A:T>G:C突变;(Iii)在复制过程中,A:T>G:C转换优先发生,A模板滞后链,T模板前导链,而G:C>答:T转变优先发生,C模板滞后链,G模板领先链;(Iv)有强烈的倾向于发生转换突变发生在5‘ApC3’/3‘TpG5’位点(其中碱基5‘A和3’T发生突变),较小程度地发生在5‘GPC3’/3‘CpG5’位点(其中碱基5‘G和3’C突变);
Knowledge of the rate and nature of spontaneous mutation is fundamental to understanding evolutionary and molecular processes. In this report, we analyze spontaneous mutations accumulated over thousands of generations by wild-type Escherichia coli and a derivative defective in mismatch repair (MMR), the primary pathway for correcting replication errors. The major conclusions are (i) the mutation rate of a wild-type E. coli strain is similar to 1 x 10(-3) per genome per generation; (ii) mutations in the wild-type strain have the expected mutational bias for G:C > A:T mutations, but the bias changes to A:T > G:C mutations in the absence of MMR; (iii) during replication, A:T > G:C transitions preferentially occur with A templating the lagging strand and T templating the leading strand, whereas G:C > A:T transitions preferentially occur with C templating the lagging strand and G templating the leading strand; (iv) there is a strong bias for transition mutations to occur at 5'ApC3'/3'TpG5' sites (where bases 5'A and 3'T are mutated) and, to a lesser extent, at 5'GpC3'/3'CpG5' sites (where bases 5'G and 3'C are mutated); (v) although the rate of small (