Pilpel Yitzhak
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Methods Mol Biol. 2011;759:407-25. doi: 10.1007/978-1-61779-173-4_23.
Genetic regulatory circuits are often regarded as precise machines that accurately determine the level of expression of each protein. Most experimental technologies used to measure gene expression levels are incapable of testing and challenging this notion, as they often measure levels averaged over entire populations of cells. Yet, when expression levels are measured at the single cell level of even genetically identical cells, substantial cell-to-cell variation (or "noise") may be observed. Sometimes different genes in a given genome may display different levels of noise; even the same gene, expressed under different environmental conditions, may display greater cell-to-cell variability in specific conditions and more tight control in other situations. While at first glance noise may seem to be an undesired property of biological networks, it might be beneficial in some cases. For instance, noise will increase functional heterogeneity in a population of microorganisms facing variable, often unpredictable, environmental changes, increasing the probability that some cells may survive the stress. In that respect, we can speculate that the population is implementing a risk distribution strategy, long before genetic heterogeneity could be acquired. Organisms may have evolved to regulate not only the averaged gene expression levels but also the extent of allowed deviations from such an average, setting it at the desired level for every gene under each specific condition. Here we review the evolving understanding of noise, its molecular underpinnings, and its effect on phenotype and fitness--when it can be detrimental, beneficial, or neutral and which regulatory tools eukaryotic cells may use to optimally control it.
基因调控回路通常被视为精确的机器，能够准确地决定每种蛋白质的表达水平。大多数用于测量基因表达水平的实验技术都无法检验和挑战这一概念，因为它们通常测量的是整个细胞群体的平均水平。然而，当在即使是基因相同的细胞的单细胞水平上测量表达水平时，可能会观察到显著的细胞间差异（或“噪音”）。有时，给定基因组中的不同基因可能表现出不同程度的噪音；即使是同一个基因，在不同的环境条件下表达，在特定条件下可能表现出更大的细胞间变异性，而在其他情况下则受到更严格的控制。乍一看，噪音似乎是生物网络的一个不良特性，但在某些情况下可能是有益的。例如，在面对多变且往往不可预测的环境变化的微生物群体中，噪音会增加功能异质性，从而增加一些细胞在压力下存活的概率。在这方面，我们可以推测，早在获得遗传异质性之前，群体就已经在实施一种风险分布策略。生物体可能已经进化到不仅可以调节平均基因表达水平，还可以调节与这种平均水平允许的偏差程度，并将其设定为每种特定条件下每个基因的期望水平。在这里，我们回顾了对噪音不断演变的理解、其分子基础以及它对表型和适应性的影响——何时它可能是有害的、有益的或中性的，以及真核细胞可能使用哪些调控工具来最佳地控制它。
