Slow-growing cells within isogenic populations have increased RNA polymerase error rates and DNA damage

David van Dijk, Riddhiman Dhar, Alsu M. Missarova, Lorena Espinar, William R. Blevins, Ben Lehner and Lucas B. Carey ()
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David van Dijk: Columbia University
Riddhiman Dhar: EMBL-CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG)
Alsu M. Missarova: Universitat Pompeu Fabra
Lorena Espinar: Universitat Pompeu Fabra
William R. Blevins: Universitat Pompeu Fabra
Ben Lehner: EMBL-CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG)
Lucas B. Carey: Universitat Pompeu Fabra

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: Abstract Isogenic cells show a large degree of variability in growth rate, even when cultured in the same environment. Such cell-to-cell variability in growth can alter sensitivity to antibiotics, chemotherapy and environmental stress. To characterize transcriptional differences associated with this variability, we have developed a method—FitFlow—that enables the sorting of subpopulations by growth rate. The slow-growing subpopulation shows a transcriptional stress response, but, more surprisingly, these cells have reduced RNA polymerase fidelity and exhibit a DNA damage response. As DNA damage is often caused by oxidative stress, we test the addition of an antioxidant, and find that it reduces the size of the slow-growing population. More generally, we find a significantly altered transcriptome in the slow-growing subpopulation that only partially resembles that of cells growing slowly due to environmental and culture conditions. Slow-growing cells upregulate transposons and express more chromosomal, viral and plasmid-borne transcripts, and thus explore a larger genotypic—and so phenotypic — space.

Date: 2015
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DOI: 10.1038/ncomms8972

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