Intrinsic and extrinsic contributions to stochasticity in gene expression.

@article{citeulike:498900, abstract = {Gene expression is a stochastic, or "noisy," process. This noise comes about in two ways. The inherent stochasticity of biochemical processes such as transcription and translation generates "intrinsic" noise. In addition, fluctuations in the amounts or states of other cellular components lead indirectly to variation in the expression of a particular gene and thus represent "extrinsic" noise. Here, we show how the total variation in the level of expression of a given gene can be decomposed into its intrinsic and extrinsic components. We demonstrate theoretically that simultaneous measurement of two identical genes per cell enables discrimination of these two types of noise. Analytic expressions for intrinsic noise are given for a model that involves all the major steps in transcription and translation. These expressions give the sensitivity to various parameters, quantify the deviation from Poisson statistics, and provide a way of fitting experiment. Transcription dominates the intrinsic noise when the average number of proteins made per mRNA transcript is greater than approximately 2. Below this number, translational effects also become important. Gene replication and cell division, included in the model, cause protein numbers to tend to a limit cycle. We calculate a general form for the extrinsic noise and illustrate it with the particular case of a single fluctuating extrinsic variable-a repressor protein, which acts on the gene of interest. All results are confirmed by stochastic simulation using plausible parameters for Escherichia coli.}, address = {Center for Studies in Physics and Biology and Laboratory for Cancer Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. swain@cnd.mcgill.ca}, author = {Swain, P. S. and Elowitz, M. B. and Siggia, E. D. }, citeulike-article-id = {498900}, doi = {10.1073/pnas.162041399}, issn = {0027-8424}, journal = {Proc Natl Acad Sci U S A}, keywords = {fluctuations, gene-expression, noise, stochasticity, theory}, month = {October}, number = {20}, pages = {12795--12800}, posted-at = {2007-01-10 13:52:43}, priority = {0}, title = {Intrinsic and extrinsic contributions to stochasticity in gene expression.}, url = {http://dx.doi.org/10.1073/pnas.162041399}, volume = {99}, year = {2002} }

TY - JOUR ID - citeulike:498900 L3 - citeulike-article-id:498900 TI - Intrinsic and extrinsic contributions to stochasticity in gene expression. JF - Proc Natl Acad Sci U S A VL - 99 IS - 20 SP - 12795 EP - 12800 AD - Center for Studies in Physics and Biology and Laboratory for Cancer Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. swain@cnd.mcgill.ca SN - 0027-8424 N2 - Gene expression is a stochastic, or "noisy," process. This noise comes about in two ways. The inherent stochasticity of biochemical processes such as transcription and translation generates "intrinsic" noise. In addition, fluctuations in the amounts or states of other cellular components lead indirectly to variation in the expression of a particular gene and thus represent "extrinsic" noise. Here, we show how the total variation in the level of expression of a given gene can be decomposed into its intrinsic and extrinsic components. We demonstrate theoretically that simultaneous measurement of two identical genes per cell enables discrimination of these two types of noise. Analytic expressions for intrinsic noise are given for a model that involves all the major steps in transcription and translation. These expressions give the sensitivity to various parameters, quantify the deviation from Poisson statistics, and provide a way of fitting experiment. Transcription dominates the intrinsic noise when the average number of proteins made per mRNA transcript is greater than approximately 2. Below this number, translational effects also become important. Gene replication and cell division, included in the model, cause protein numbers to tend to a limit cycle. We calculate a general form for the extrinsic noise and illustrate it with the particular case of a single fluctuating extrinsic variable-a repressor protein, which acts on the gene of interest. All results are confirmed by stochastic simulation using plausible parameters for Escherichia coli. KW - fluctuations KW - gene-expression KW - noise KW - stochasticity KW - theory AU - Swain, PS AU - Elowitz, MB AU - Siggia, ED PY - 2002/10/01/ UR - http://dx.doi.org/10.1073/pnas.162041399 ER -