1. Computational and Systems Biology
  2. Microbiology and Infectious Disease
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Initiation of chromosome replication controls both division and replication cycles in E. coli through a double-adder mechanism

  1. Guillaume Witz  Is a corresponding author
  2. Erik van Nimwegen
  3. Thomas Julou
  1. University of Basel, Switzerland
Research Article
  • Cited 13
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Cite this article as: eLife 2019;8:e48063 doi: 10.7554/eLife.48063


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

Article and author information

Author details

  1. Guillaume Witz

    Biozentrum, University of Basel, Basel, Switzerland
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1562-4265
  2. Erik van Nimwegen

    Biozentrum, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Thomas Julou

    Biozentrum, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.


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.

Reviewing Editor

  1. Michael T Laub, Massachusetts Institute of Technology, United States

Publication history

  1. Received: April 30, 2019
  2. Accepted: November 7, 2019
  3. Accepted Manuscript published: November 11, 2019 (version 1)
  4. Version of Record published: December 3, 2019 (version 2)


© 2019, Witz et al.

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.


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