Zaslaver Alon, Kaplan Shai, Bren Anat, Jinich Adrian, Mayo Avi, Dekel Erez, Alon Uri, Itzkovitz Shalev
Division of Biology, California Institute of Technology, Pasadena, California, United States of America.
PLoS Comput Biol. 2009 Oct;5(10):e1000545. doi: 10.1371/journal.pcbi.1000545. Epub 2009 Oct 23.
Cells need to allocate their limited resources to express a wide range of genes. To understand how Escherichia coli partitions its transcriptional resources between its different promoters, we employ a robotic assay using a comprehensive reporter strain library for E. coli to measure promoter activity on a genomic scale at high-temporal resolution and accuracy. This allows continuous tracking of promoter activity as cells change their growth rate from exponential to stationary phase in different media. We find a heavy-tailed distribution of promoter activities, with promoter activities spanning several orders of magnitude. While the shape of the distribution is almost completely independent of the growth conditions, the identity of the promoters expressed at different levels does depend on them. Translation machinery genes, however, keep the same relative expression levels in the distribution across conditions, and their fractional promoter activity tracks growth rate tightly. We present a simple optimization model for resource allocation which suggests that the observed invariant distributions might maximize growth rate. These invariant features of the distribution of promoter activities may suggest design constraints that shape the allocation of transcriptional resources.
细胞需要分配其有限的资源来表达各种各样的基因。为了了解大肠杆菌如何在其不同启动子之间分配转录资源，我们采用了一种机器人检测方法，使用一个针对大肠杆菌的综合报告菌株文库，以高时间分辨率和准确性在基因组规模上测量启动子活性。这使得我们能够在细胞在不同培养基中从指数生长期转变为稳定期时持续追踪启动子活性。我们发现启动子活性呈重尾分布，启动子活性跨越几个数量级。虽然分布的形状几乎完全独立于生长条件，但不同水平表达的启动子的身份确实取决于生长条件。然而，翻译机制基因在不同条件下的分布中保持相同的相对表达水平，并且它们的启动子活性分数与生长速率紧密相关。我们提出了一个简单的资源分配优化模型，该模型表明观察到的不变分布可能使生长速率最大化。启动子活性分布的这些不变特征可能暗示了塑造转录资源分配的设计限制。
