Protein overabundance is driven by growth robustness

Abstract: 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 depleted by dilution from wild-type expression 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. 

Biosketch: Paul A. Wiggins, Ph.D., Associate Professor of Physics, Bioengineering and Microbiology. Dr. Wiggins studied Applied and Engineering Physics at Cornell University, before receiving a PhD in Physics at the California Institute of Technology. Dr. Wiggins took a Fellows position at the Whitehead Institute of Biomedical Research for five years where he led an independent research lab, before accepting an assistant professorship in 2010 and moving his lab to the University of Washington in the Physics, Bioengineering and Microbiology Departments. Dr. Wiggins became an associate professor in 2016. The primary focus of the Wiggins Lab is biophysics and quantitative biology, particularly focused on bacterial ultrastructure, chromosome structure and replication. The lab has expertise in imaging, experimental biophysics as well as modeling and theory. In recent years the lab has forged collaborations with the Dove, Mougous, Manoil, Traxler and Merrikh labs to focus on quantitative approaches to wide range of microbiology problems.