Fitness cost of fluctuations in bacterial gene expression
by
Måns Ehrenberg(Uppsala University)
→
Europe/Stockholm
Description
When E. coli bacteria grow in amino acid lacking media, the twenty canonical amino acids are synthesized in twenty, semi-independent metabolic pathways. Constitutive expression of the enzymes in these pathways leads to Poisson distributed messenger RNA (mRNA) and Negative Binomial distributed enzyme copy numbers per cell. The pathway which by random protein copy number fluctuations has the smallest rate of amino acid synthesis in relation to amino acid demand in protein synthesis, will determine the total rate of protein synthesis and thus the growth rate of the cell: the existence of many parallel metabolic pathways in growing bacteria greatly increases the fitness cost of enzyme copy number fluctuations since the “worst” random scenario is always sampled. This suggests that noise taming may be the most important task of intracellular feed-back loops for gene expression, opening the possibility to judge the quality of these control systems by their ability to reduce the fitness cost of intrinsic noise.
Amino acid synthesis is controlled by transcriptional repressors, sensing the current amino acid concentrations, or ribosome dependent transcription attenuators, sensing ribosome speed at amino acid starved codons. Repressor
control reduces the fitness cost of random fluctuations to an extent determined by their amino acid affinity and their sensitivity to amino acid concentration changes. We discuss optimal solutions to amino acid control in terms of minimization of the fitness cost of random fluctuations in gene expression.
