1. Evolutionary Biology
  2. Genetics and Genomics
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The evolutionary plasticity of chromosome metabolism allows adaptation to constitutive DNA replication stress

  1. Marco Fumasoni  Is a corresponding author
  2. Andrew W Murray
  1. Harvard University, United States
Research Article
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Cite this article as: eLife 2020;9:e51963 doi: 10.7554/eLife.51963

Abstract

Many biological features are conserved and thus considered to be resistant to evolutionary change. While rapid genetic adaptation following the removal of conserved genes has been observed, we often lack a mechanistic understanding of how adaptation happens. We used the budding yeast, Saccharomyces cerevisiae, to investigate the evolutionary plasticity of chromosome metabolism, a network of evolutionary conserved modules. We experimentally evolved cells constitutively experiencing DNA replication stress caused by the absence of Ctf4, a protein that coordinates the enzymatic activities at replication forks. Parallel populations adapted to replication stress, over 1000 generations, by acquiring multiple, concerted mutations. These mutations altered conserved features of two chromosome metabolism modules, DNA replication and sister chromatid cohesion, and inactivated a third, the DNA damage checkpoint. The selected mutations define a functionally reproducible evolutionary trajectory. We suggest that the evolutionary plasticity of chromosome metabolism has implications for genome evolution in natural populations and cancer.

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Author details

  1. Marco Fumasoni

    Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    For correspondence
    marcofumasoni@fas.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4507-7824
  2. Andrew W Murray

    Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0868-6604

Funding

Human Frontier Science Program (LT000786/2016-L)

  • Marco Fumasoni

European Molecular Biology Organization (ALTF 485-2015)

  • Marco Fumasoni

Fondazione AIRC per la ricerca sul cancro (iCARE 17957)

  • Marco Fumasoni

National Institute of General Medical Sciences (RO1-GM43987)

  • Andrew W Murray

NSF-Simons Center for Mathematical and Statistical Analysis of Biology at Harvard (#1764269)

  • Andrew W Murray

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

Reviewing Editor

  1. Kevin J Verstrepen, VIB-KU Leuven Center for Microbiology, Belgium

Publication history

  1. Received: September 17, 2019
  2. Accepted: February 11, 2020
  3. Accepted Manuscript published: February 11, 2020 (version 1)

Copyright

© 2020, Fumasoni & Murray

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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