article · 26/07/2018
Mutation rates and effects in single cells
Résumé
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.
Citer cet article
Robert, L., Ollion, J., Robert, J., Song, X., Matic, I., & Elez, M. (2018). Mutation rates and effects in single cells. Science, 359(6381), 1283-1286. https://doi.org/10.1126/science.aan0797@article{Robert2018_277,
author = {Robert, Lydia and Ollion, Jean and Robert, Jerome and Song, Xiaohu and Matic, Ivan and Elez, Marina},
year = {2018},
month = {7},
title = {Mutation rates and effects in single cells},
journal = {Science},
volume = {359},
number = {6381},
pages = {1283-1286},
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 \textasciitilde{}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.},
doi = {10.1126/science.aan0797},
}TY - JOUR
AU - Robert, Lydia
AU - Ollion, Jean
AU - Robert, Jerome
AU - Song, Xiaohu
AU - Matic, Ivan
AU - Elez, Marina
PY - 2018
DA - 2018/07/26
TI - Mutation rates and effects in single cells
JO - Science
VL - 359
IS - 6381
AB - 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.
SP - 1283
EP - 1286
DO - 10.1126/science.aan0797
ER -