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Codon-dependent noise dictates cell-to-cell variability in nutrient poor environments

Enrique Balleza, Lisa F. Marshall, J. Mark Kim, View ORCID ProfilePhilippe Cluzel
doi: https://doi.org/10.1101/492207
Enrique Balleza
Department of Molecular and Cellular Biology, SEAS, Harvard University, Cambridge, Massachusetts, USA
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Lisa F. Marshall
Department of Molecular and Cellular Biology, SEAS, Harvard University, Cambridge, Massachusetts, USA
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J. Mark Kim
Department of Molecular and Cellular Biology, SEAS, Harvard University, Cambridge, Massachusetts, USA
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Philippe Cluzel
Department of Molecular and Cellular Biology, SEAS, Harvard University, Cambridge, Massachusetts, USA
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  • ORCID record for Philippe Cluzel
  • For correspondence: cluzel@mcb.harvard.edu
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Abstract

Under nutrient-rich conditions, stochasticity of transcription drives protein expression noise. However, by shifting the environment to amino acid-limited conditions, we identified in E. coli a source of noise whose strength is dictated by translational processes. Specifically, we discovered that cell-to-cell variations in fluorescent protein expression depend on codon choice, with codons yielding lower mean expression after amino acid downshift also resulting in greater noise. We propose that ultra-sensitivity in the tRNA charging/discharging cycle shapes the strength of the observed noise by amplifying fluctuations in global intracellular parameters, such as the concentrations of amino acid, synthetase, and tRNA. We hypothesize that this codon-dependent noise may allow bacteria to selectively optimize cell-to-cell variability in poor environments without relying on low molecular numbers.

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Posted December 10, 2018.
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Codon-dependent noise dictates cell-to-cell variability in nutrient poor environments
Enrique Balleza, Lisa F. Marshall, J. Mark Kim, Philippe Cluzel
bioRxiv 492207; doi: https://doi.org/10.1101/492207
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Codon-dependent noise dictates cell-to-cell variability in nutrient poor environments
Enrique Balleza, Lisa F. Marshall, J. Mark Kim, Philippe Cluzel
bioRxiv 492207; doi: https://doi.org/10.1101/492207

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