Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel.
Nat Commun. 2019 Jan 8;10(1):68. doi: 10.1038/s41467-018-07391-8.
Steady-state protein abundance is set by four rates: transcription, translation, mRNA decay and protein decay. A given protein abundance can be obtained from infinitely many combinations of these rates. This raises the question of whether the natural rates for each gene result from historical accidents, or are there rules that give certain combinations a selective advantage? We address this question using high-throughput measurements in rapidly growing cells from diverse organisms to find that about half of the rate combinations do not exist: genes that combine high transcription with low translation are strongly depleted. This depletion is due to a trade-off between precision and economy: high transcription decreases stochastic fluctuations but increases transcription costs. Our theory quantitatively explains which rate combinations are missing, and predicts the curvature of the fitness function for each gene. It may guide the design of gene circuits with desired expression levels and noise.
转录、翻译、mRNA 降解和蛋白质降解。给定的蛋白质丰度可以通过这些速率的无限组合获得。这就提出了一个问题，即每个基因的自然速率是源于历史偶然，还是存在一些规则赋予某些组合选择性优势？我们使用来自不同生物的快速生长细胞中的高通量测量来解决这个问题，发现大约一半的速率组合不存在：高转录与低翻译相结合的基因被强烈耗尽。这种消耗是由于精度和经济性之间的权衡：高转录降低了随机波动，但增加了转录成本。我们的理论定量解释了哪些速率组合缺失，并预测了每个基因的适应性函数的曲率。它可以指导具有所需表达水平和噪声的基因电路的设计。
