Protein overabundance is driven by growth robustness

Protein expression levels optimize cell fitness: Too low an expression level of essential proteins will slow growth by compromising essential processes; whereas overexpression slows growth by increasing the metabolic load. This trade-off naively predicts that cells maximize their fitness by sufficie...

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Bibliographic Details
Published inarXiv.org
Main Authors Choi, H James, Lo, Teresa W, Cutler, Kevin J, Huang, Dean, W Ryan Will, Wiggins, Paul A
Format Paper
LanguageEnglish
Published Ithaca Cornell University Library, arXiv.org 21.08.2024
Subjects
Gene expression
Predictions
Proteins
Robustness
Tradeoffs
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Summary:Protein expression levels optimize cell fitness: Too low an expression level of essential proteins will slow growth by compromising essential processes; whereas overexpression slows growth by increasing the metabolic load. This trade-off naively predicts that cells maximize their fitness by sufficiency, expressing just enough of each essential protein for function. We test this prediction in the naturally-competent bacterium Acinetobacter baylyi by characterizing the proliferation dynamics of essential-gene knockouts at a single-cell scale (by imaging) as well as at a genome-wide scale (by TFNseq). In these experiments, cells proliferate for multiple generations as target protein levels are diluted from their endogenous levels. This approach facilitates a proteome-scale analysis of protein overabundance. As predicted by the Robustness-Load Trade-Off (RLTO) model, we find that roughly 70% of essential proteins are overabundant and that overabundance increases as the expression level decreases, the signature prediction of the model. These results reveal that robustness plays a fundamental role in determining the expression levels of essential genes and that overabundance is a key mechanism for ensuring robust growth.
ISSN:2331-8422