  The processes of gene expression are inherently stochastic, even for
essential genes required for growth. How does the cell maximize fitness in
light of noise? To answer this question, we build a mathematical model to
explore the trade-off between metabolic load and growth robustness. The model
predicts novel principles of central dogma regulation: Optimal protein
expression levels for many genes are in vast overabundance. Essential genes are
transcribed above a lower limit of one message per cell cycle. Gene expression
is achieved by load balancing between transcription and translation. We present
evidence that each of these novel regulatory principles is observed. These
results reveal that robustness and metabolic load determine the global
regulatory principles that govern central dogma function, and these principles
have broad implications for cellular function.
