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Mutation dynamics and fitness effects followed in single cells

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Science  16 Mar 2018:
Vol. 359, Issue 6381, pp. 1283-1286
DOI: 10.1126/science.aan0797

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Mutation rates and effects in single cells

Understanding the dynamics of mutations and the distribution of fitness effects is critical for most evolutionary models. Robert et al. used a single-cell technology to visualize the accumulation of new mutations. The method identifies DNA sequences with mispaired bases and small insertions or deletions caused by DNA replication errors in living Escherichia coli cells. Following the fates of cells after mutation allowed for a precise quantification of the effects of new mutations. A smaller fraction of mutations were found to be deleterious than predicted previously from indirect observations.

Science, this issue p. 1283

Abstract

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 ~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.

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