Medical and Biological Physics(DMBP)
Physique médicale et biologique (DPMB)

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Peter S. SWAIN
McGill University

Stochastic Gene Expression in Single Cells

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Generation of variability in populations of cells, all of which have the same genome, is essential for many biological processes. Such heterogeneity is conjectured to arise from stochasticity, or noise, in gene expression. We show theoretically that noise can be decomposed into an intrinsic piece, particular to a given gene, and an extrinsic term, common to all genes in a cell, but variable from one cell to another. Using specially constructed strains of Escherichia coli, we are able to discriminate between, and measure, both types of noise. We demonstrate that intrinsic noise indeed exists in vivo and accounts for a substantial portion of cell-cell variation. An analytical description of gene expression is also presented, which contains all the major biochemical steps in transcription and translation. As transcription rate is varied, this model confirms experimental findings that the amplitudes of both noise components vary over a wide range. These results reveal how low intracellular copy numbers can fundamentally limit the precision of gene expression.