Evolution of design principles in biochemical networks

Atauri, Pedro de; Orrell, David; Ramsey, Stephen A.; Bolouri, Hamid

doi:10.1049/sb:20045013

Cited by 31 publications

(41 citation statements)

References 61 publications

(87 reference statements)

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“…Based on our results we suggest that, as the sequestration of Gal80 protein proceeds, GAL7 and GAL10 transcription ensues first, followed by GAL1. This temporal expression pattern ensures that toxicity due to the accumulation of galactose-1-phosphate (De Atauri et al 2004) does not occur at any time during induction.…”

Section: Discussionmentioning

confidence: 99%

Replacement of a conserved tyrosine by tryptophan in Gal3p of Saccharomyces cerevisiae reduces constitutive activity: implications for signal transduction in the GAL regulon

Lakshminarasimhan

Bhat

2005

Mol Genet Genomics

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The ability of Saccharomyces cerevisiae to utilize galactose is regulated by the nucleo-cytoplasmic shuttling of a transcriptional repressor, the Gal80 protein. Gal80 interacts with the transcriptional activator Gal4 in the nucleus and inhibits its function, preventing induction of the GAL genes. In response to galactose, the relative amounts of Gal80 in the cytoplasm and the nucleus are modulated by the action of a signal transducer, Gal3. Although it has been speculated that Gal3 binds galactose, this has not been experimentally demonstrated. In this study, we show that replacement of a conserved tyrosine in Gal3 by tryptophan leads to a reduction of its constitutive activity in the absence of galactose. In addition, this mutant protein was fully functional in vivo only when high concentrations of galactose were present in the medium. When overexpressed, the mutant was found to activate the genes GAL1 and GAL7/10 differentially. The implications of these findings for the fine regulation of GAL genes, and its physiological significance, are discussed.

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Section: Discussionmentioning

confidence: 99%

Replacement of a conserved tyrosine by tryptophan in Gal3p of Saccharomyces cerevisiae reduces constitutive activity: implications for signal transduction in the GAL regulon

Lakshminarasimhan

Bhat

2005

Mol Genet Genomics

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“…The model used is as described in our previous study [38], except as indicated here. For the mutant strain, we modified the fractional saturation for GAL3 and GAL80 to a fixed value of 0.04.…”

Section: Methodsmentioning

confidence: 99%

Feedback control of stochastic noise in the yeast galactose utilization pathway

Orrell

Ramsey

Marelli

et al. 2006

Physica D: Nonlinear Phenomena

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Genetic networks are often affected by stochastic noise, due to the low number of molecules taking part in certain reactions. In complex regulatory networks, noise in any one chemical species may induce noise in the rest of the system. In this paper, we analyse the sources of stochastic noise in the yeast galactose utilization pathway at the level of the complete system, by using both computer simulations, and experimental comparisons 2 between wild-type yeast and a modified strain. A computer model was first used to determine the sources of network noise, as well as mechanisms by which noise is controlled. Results from an estimation tool, confirmed by detailed stochastic simulations, show that noise is caused primarily by fluctuations in mRNA concentrations due to their stochastic creation and decay. The noise is controlled by feedback loops which regulate transcription of certain genes. To test the effect of the feedback loops on the rest of the system, a modified strain of yeast was prepared in which regulation of two key genes is eliminated. As predicted by the model, the mutant strain is induced by galactose in a manner similar to the wild type, but with a higher degree of stochastic noise.

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“…Fig. (2) was derived manually from the literature [15]. Accompanying this figure are biochemical and mathematical descriptions, which uniquely and unambiguously define the nature of the interactions within this system and the resulting dynamic behavior.…”

Section: Higher-level Abstractions Need a Functional Basismentioning

confidence: 99%

Understanding the Dynamic Behavior of Genetic Regulatory Networks by Functional Decomposition

Longabaugh

Bolouri²

2006

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A number of mechanistic and predictive genetic regulatory networks (GRNs) comprising dozens of genes have already been characterized at the level of cis-regulatory interactions. Reconstructions of networks of 100's to 1000's of genes and their interactions are currently underway. Understanding the organizational and functional principles underlying these networks is probably the single greatest challenge facing genomics today. We review the current approaches to deciphering large-scale GRNs and discuss some of their limitations. We then propose a bottom-up approach in which large-scale GRNs are first organized in terms of functionally distinct GRN building blocks of one or a few genes. Biological processes may then be viewed as the outcome of functional interactions among these simple, well-characterized functional building blocks. We describe several putative GRN functional building blocks and show that they can be located within GRNs on the basis of their interaction topology and additional, simple and experimentally testable constraints.

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Evolution of design principles in biochemical networks

Cited by 31 publications

References 61 publications

Replacement of a conserved tyrosine by tryptophan in Gal3p of Saccharomyces cerevisiae reduces constitutive activity: implications for signal transduction in the GAL regulon

Replacement of a conserved tyrosine by tryptophan in Gal3p of Saccharomyces cerevisiae reduces constitutive activity: implications for signal transduction in the GAL regulon

Feedback control of stochastic noise in the yeast galactose utilization pathway

Understanding the Dynamic Behavior of Genetic Regulatory Networks by Functional Decomposition

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