Mutation dynamics and fitness effects followed in single cells
Mutation dynamics and fitness effects followed in single cells
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DOI：
10.1126/science.aan0797
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发表时间：
2018-03-16
期刊：
影响因子：
56.9
通讯作者：
Elez, Marina
中科院分区：
文献类型：
--
作者：
Robert, Lydia;Ollion, Jean;Elez, Marina
突变的研究已经有一个多世纪了，但仍然很难在单细胞中直接观察，这限制了其动态和适应性效应的表征。通过结合微流体、延时成像和大肠杆菌错配修复系统的荧光标签，我们可视化了单细胞中突变的出现，揭示了泊松动力学。与此同时，我们追踪了单细胞的生长和寿命，在数百代的时间里在全基因组范围内积累了大约 20,000 个突变。该分析表明，1% 的突变是致命的；非致死突变表现出适应度效应的重尾分布，并且以准中性突变为主，平均成本为 0.3%。我们的方法使得能够研究单细胞个体在突变率、突变适应度成本和突变相互作用方面的研究。
Mutations have been investigated for more than a century but remain difficult to observe directly in single cells, which limits the characterization of their dynamics and fitness effects. By combining microfluidics, time-lapse imaging, and a fluorescent tag of the mismatch repair system in Escherichia coli, we visualized the emergence of mutations in single cells, revealing Poissonian dynamics. Concomitantly, we tracked the growth and life span of single cells, accumulating similar to 20,000 mutations genome-wide over hundreds of generations. This analysis revealed that 1% of mutations were lethal; nonlethal mutations displayed a heavy-tailed distribution of fitness effects and were dominated by quasi-neutral mutations with an average cost of 0.3%. Our approach has enabled the investigation of single-cell individuality in mutation rate, mutation fitness costs, and mutation interactions.