The evolutionary plasticity of chromosome metabolism allows adaptation to constitutive DNA replication stress
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.
Data availability
A major dataset, containing the sequencing data used in the manuscript has been made publicly available at the EBI European Nucleotide Archive (Accession no: PRJEB34641)
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Sequences from The evolutionary plasticity of chromosome metabolism allows adaptation to constitutive DNA replication stressEBI European Nucleotide Archive, PRJEB34641.
Article and author information
Author details
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.
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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