Joint Centers for Systems Biology, Columbia University, New York, New York, United States of America.
PLoS Genet. 2012 May;8(5):e1002744. doi: 10.1371/journal.pgen.1002744. Epub 2012 May 31.
Regulatory networks allow organisms to match adaptive behavior to the complex and dynamic contingencies of their native habitats. Upon a sudden transition to a novel environment, the mismatch between the native behavior and the new niche provides selective pressure for adaptive evolution through mutations in elements that control gene expression. In the case of core components of cellular regulation and metabolism, with broad control over diverse biological processes, such mutations may have substantial pleiotropic consequences. Through extensive phenotypic analyses, we have characterized the systems-level consequences of one such mutation (rho*) in the global transcriptional terminator Rho of Escherichia coli. We find that a single amino acid change in Rho results in a massive change in the fitness landscape of the cell, with widely discrepant fitness consequences of identical single locus perturbations in rho* versus rho(WT) backgrounds. Our observations reveal the extent to which a single regulatory mutation can transform the entire fitness landscape of the cell, causing a massive change in the interpretation of individual mutations and altering the evolutionary trajectories which may be accessible to a bacterial population.
调控网络使生物能够根据其原生栖息地的复杂和动态变化来匹配适应性行为。当突然过渡到新环境时，原生行为与新生态位之间的不匹配为通过控制基因表达的元件的突变提供了适应性进化的选择压力。在细胞调控和代谢的核心组成部分的情况下，由于对多种生物过程具有广泛的控制，这种突变可能会产生大量的多效性后果。通过广泛的表型分析，我们已经描述了大肠杆菌全局转录终止子 Rho 中一个这样的突变 (rho*) 的系统水平后果。我们发现，Rho 中的单个氨基酸变化导致细胞的适应度景观发生巨大变化，在 rho* 与 rho(WT)背景下相同单一位点干扰的适应性后果存在广泛差异。我们的观察结果揭示了单个调控突变可以在多大程度上改变细胞的整个适应度景观，导致对单个突变的解释发生巨大变化，并改变可能对细菌种群可及的进化轨迹。
