Feb 3, 2015

A mechanistic link between cellular trade-offs, gene expression and growth

BioRxiv : the Preprint Server for Biology
Andrea Y. WeissePeter S. Swain

Abstract

Intracellular processes rarely work in isolation but continually, interact with the rest of the cell. In microbes, for example, we now know that gene expression across the whole genome typically changes with growth rate. The mechanisms driving such global regulation, however, are not well understood. Here we consider three trade-offs that because of limitations in levels of cellular energy, free ribosomes, and proteins are faced by all living cells and construct a mechanistic model that comprises these trade-offs. Our model couples gene expression with growth rate and growth rate with a growing population of cells. We show that the model recovers Monod's law for the growth of microbes and two other empirical relationships connecting growth rate to the mass fraction of ribosomes. Further, we can explain growth related effects in dosage compensation by paralogs and predict host-circuit interactions in synthetic biology. Simulating competitions between strains, we find that the regulation of metabolic pathways may have evolved not to match expression of enzymes to levels of extracellular substrates in changing environments but rather to balance a trade-off between exploiting one type of nutrient over another. Although coarse-grain...Continue Reading

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Mentioned in this Paper

Energy Transfer
Criminal Law
Genome
Extracellular
Enzymes, antithrombotic
Regulation of Biological Process
Isolation Aspects
Protoplasm
Environment
Gene Dosage Compensation Mechanism

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