Initiation of chromosome replication controls both division and replication cycles in E. coli through a double-adder mechanism

Abstract
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Abstract

Living cells proliferate by completing and coordinating two cycles, a division cycle controlling cell size, and a DNA replication cycle controlling the number of chromosomal copies. It remains unclear how bacteria such as E. coli tightly coordinate those two cycles across a wide range of growth conditions. Here, we used time-lapse microscopy in combination with microfluidics to measure growth, division and replication in single E. coli cells in slow and fast growth conditions. To compare different phenomenological cell cycle models, we introduce a statistical framework assessing their ability to capture the correlation structure observed in the data. In combination with stochastic simulations, our data indicate that the cell cycle runs from one initiation event to the next rather than from birth to division and is controlled by two adder mechanisms: the added volume since the last initiation event determines the timing of both the next division and replication initiation events.

Data availability

Images of growth channels and MoMA segmentations have been deposited on Zenodo.

The following data sets were generated

(2019) Analysis of division and replication cycles in E. coli using time-lapse microscopy, microfluidics and the MoMA software
Zenodo, doi:10.5281/zenodo.3149097.

https://doi.org/10.5281/zenodo.3149097

Article and author information

Author details

Guillaume Witz

Biozentrum, University of Basel, Basel, Switzerland

For correspondence
guillaume.witz@math.unibe.ch

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1562-4265
Erik van Nimwegen

Biozentrum, University of Basel, Basel, Switzerland

Competing interests
The authors declare that no competing interests exist.
Thomas Julou

Biozentrum, University of Basel, Basel, Switzerland

Competing interests
The authors declare that no competing interests exist.

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (PZ00P3_161467)

Guillaume Witz

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_159673)

Erik van Nimwegen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.