When is "just right" also "much more than enough"? Surprising lessons on optimality from a bacterium

What rationale explains protein abundances in the cell? Optimizing cell fitness would seem to predict that protein abundances should be “just enough” due to the trade off between achieving function while minimizing the load from the expression of unnecessary protein; however, recent experiments demonstrate order-of-magnitude reductions in essential protein abundances without reductions in cell fitness. How can this observed essential protein overabundance be rationalized? In this talk, I will present an analytically-tractable model for the role of gene expression in cell fitness. The model describes the trade-off between protein function and metabolic load and predicts three novel principles that optimize gene expression, including a prediction that vast overabundance is optimal for low-expression essential proteins. I will present evidence for each of these proposed principles in a range of organisms, including measurements with single-cell resolution as well as a proteome-wide approach that characterizes essential protein overabundance in the emerging model bacterium Acinetobacter baylyi. The observed protein overabundance has important biological implications for understanding the function of many biological processes, including determining which proteins are the most attractive targets for antibacterial drugs.