Noise robustness and metabolic load determine the principles of central dogma regulation
Noise robustness and metabolic load determine the principles of central dogma regulation
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DOI：
10.1126/sciadv.ado3095
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发表时间：
2024-08-23
期刊：
影响因子：
13.6
通讯作者：
Wiggins，Paul A.
中科院分区：
文献类型：
--
作者：
Lo，Teresa W.;Choi，H. James;Wiggins，Paul A.
基因表达的过程本质上是随机的，即使对于生长所需的必需基因也是如此。细胞如何在噪音的情况下最大化适应度？为了回答这个问题，我们建立了一个数学模型来探索代谢负荷和生长稳健性之间的权衡。该模型为中心法则调节原理提供了见解：许多基因的最佳蛋白质表达水平都非常丰富。必需基因的转录高于每个细胞周期一条信息的下限。基因表达是通过转录和翻译之间的负载平衡来实现的。我们提供证据证明这些监管原则均得到遵守。这些结果表明，稳健性和代谢负荷决定了控制基因表达过程的全局调控原则，这些原则对细胞功能具有广泛的影响。
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.