1. Computational and Systems Biology
  2. Microbiology and Infectious Disease
Download icon

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 3
  • Views 2,421
  • Annotations
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.

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.


  • 2,421
    Page views
  • 393
  • 3

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Computational and Systems Biology
    Lucile Megret et al.
    Research Article

    Loss of cellular homeostasis has been implicated in the etiology of several neurodegenerative diseases (NDs). However, the molecular mechanisms that underlie this loss remain poorly understood on a systems level in each case. Here, using a novel computational approach to integrate dimensional RNA-seq and in vivo neuron survival data, we map the temporal dynamics of homeostatic and pathogenic responses in four striatal cell types of Huntington’s disease (HD) model mice. This map shows that most pathogenic responses are mitigated and most homeostatic responses are decreased over time, suggesting that neuronal death in HD is primarily driven by the loss of homeostatic responses. Moreover, different cell types may lose similar homeostatic processes, for example, endosome biogenesis and mitochondrial quality control in Drd1-expressing neurons and astrocytes. HD relevance is validated by human stem cell, genome-wide association study, and post-mortem brain data. These findings provide a new paradigm and framework for therapeutic discovery in HD and other NDs.

    1. Cell Biology
    2. Computational and Systems Biology
    Taraneh Zarin et al.
    Research Advance

    In previous work, we showed that intrinsically disordered regions (IDRs) of proteins contain sequence-distributed molecular features that are conserved over evolution, despite little sequence similarity that can be detected in alignments (Zarin et al. 2019). Here, we aim to use these molecular features to predict specific biological functions for individual IDRs and identify the molecular features within them that are associated with these functions. We find that the predictable functions are diverse. Examining the associated molecular features, we note some that are consistent with previous reports, and identify others that were previously unknown. We experimentally confirm that elevated isoelectric point and hydrophobicity, features that are positively associated with mitochondrial localization, are necessary for mitochondrial targeting function. Remarkably, increasing isoelectric point in a synthetic IDR restores weak mitochondrial targeting. We believe feature analysis represents a new systematic approach to understand how biological functions of IDRs are specified by their protein sequences.