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Noise robustness and metabolic load determine the principles of central dogma regulation.

ABSTRACT: The processes of gene expression are inherently stochastic, even for essential genes required for growth. How does the cell maximize fitness in light of noise? To answer this question, we build a mathematical model to explore the trade-off between metabolic load and growth robustness. The model provides insights for principles of central dogma regulation: Optimal protein expression levels for many genes are in vast overabundance. Essential genes are transcribed above a lower limit of one message per cell cycle. Gene expression is achieved by load balancing between transcription and translation. We present evidence that each of these regulatory principles is observed. These results reveal that robustness and metabolic load determine the global regulatory principles that govern gene expression processes, and these principles have broad implications for cellular function.

SUBMITTER: Lo TW

PROVIDER: S-EPMC11343026 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Noise robustness and metabolic load determine the principles of central dogma regulation.

Lo Teresa W TW Choi H James HJ Huang Dean D Wiggins Paul A PA

Science advances 20240823 34

The processes of gene expression are inherently stochastic, even for essential genes required for growth. How does the cell maximize fitness in light of noise? To answer this question, we build a mathematical model to explore the trade-off between metabolic load and growth robustness. The model provides insights for principles of central dogma regulation: Optimal protein expression levels for many genes are in vast overabundance. Essential genes are transcribed above a lower limit of one message ...[more]

PMID: 39178264

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Noise robustness and metabolic load determine the principles of central dogma regulation.

Project description:The processes of gene expression are inherently stochastic, even for essential genes required for growth. How does the cell maximize fitness in light of noise? To answer this question, we build a mathematical model to explore the trade-off between metabolic load and growth robustness. The model predicts novel principles of central dogma regulation: Optimal protein expression levels are vastly overabundant. Essential genes are transcribed above a lower limit of one message per cell cycle. Gene expression is achieved by load balancing between transcription and translation. We show that each of these novel regulatory principles is observed. These results reveal that robustness and metabolic load determine the global regulatory principles that govern central dogma processes, and these principles have broad implications for cellular function.

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Beyond the Central Dogma: Model-Based Learning of How Genes Determine Phenotypes.

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Teaching the Central Dogma of Molecular Biology using Jewelry.

Project description: Not available

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Revisiting the central dogma one molecule at a time.

Project description:The faithful relay and timely expression of genetic information depend on specialized molecular machines, many of which function as nucleic acid translocases. The emergence over the last decade of single-molecule fluorescence detection and manipulation techniques with nm and Å resolution and their application to the study of nucleic acid translocases are painting an increasingly sharp picture of the inner workings of these machines, the dynamics and coordination of their moving parts, their thermodynamic efficiency, and the nature of their transient intermediates. Here we present an overview of the main results arrived at by the application of single-molecule methods to the study of the main machines of the central dogma.

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Large-scale 13C-flux analysis reveals mechanistic principles of metabolic network robustness to null mutations in yeast.

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