Løvdok Linda, Bentele Kajetan, Vladimirov Nikita, Müller Anette, Pop Ferencz S, Lebiedz Dirk, Kollmann Markus, Sourjik Victor
Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Heidelberg, Germany.
PLoS Biol. 2009 Aug;7(8):e1000171. doi: 10.1371/journal.pbio.1000171. Epub 2009 Aug 18.
Chemotaxis allows bacteria to colonize their environment more efficiently and to find optimal growth conditions, and is consequently under strong evolutionary selection. Theoretical and experimental analyses of bacterial chemotaxis suggested that the pathway has been evolutionarily optimized to produce robust output under conditions of such physiological perturbations as stochastic intercellular variations in protein levels while at the same time minimizing complexity and cost of protein expression. Pathway topology in Escherichia coli apparently evolved to produce an invariant output under concerted variations in protein levels, consistent with experimentally observed transcriptional coupling of chemotaxis genes. Here, we show that the pathway robustness is further enhanced through the pairwise translational coupling of adjacent genes. Computer simulations predicted that the robustness of the pathway against the uncorrelated variations in protein levels can be enhanced by a selective pairwise coupling of individual chemotaxis genes on one mRNA, with the order of genes in E. coli ranking among the best in terms of noise compensation. Translational coupling between chemotaxis genes was experimentally confirmed, and coupled expression of these genes was shown to improve chemotaxis. Bioinformatics analysis further revealed that E. coli gene order corresponds to consensus in sequenced bacterial genomes, confirming evolutionary selection for noise reduction. Since polycistronic gene organization is common in bacteria, translational coupling between adjacent genes may provide a general mechanism to enhance robustness of their signaling and metabolic networks. Moreover, coupling between expression of neighboring genes is also present in eukaryotes, and similar principles of noise reduction might thus apply to all cellular networks.
趋化作用使细菌能够更有效地在其环境中定殖并找到最佳生长条件，因此受到强烈的进化选择。对细菌趋化作用的理论和实验分析表明，该信号通路在进化过程中得到了优化，以便在诸如蛋白质水平的随机细胞间差异等生理扰动条件下产生稳健的输出，同时将蛋白质表达的复杂性和成本降至最低。大肠杆菌中的信号通路拓扑结构显然是在蛋白质水平协同变化的情况下进化而来，以产生不变的输出，这与实验观察到的趋化作用基因的转录偶联一致。在这里，我们表明，通过相邻基因的成对翻译偶联，信号通路的稳健性进一步增强。计算机模拟预测，通过单个趋化作用基因在一个信使核糖核酸上的选择性成对偶联，可以增强信号通路对蛋白质水平不相关变化的稳健性，就噪声补偿而言，大肠杆菌中基因的排列顺序是最佳的之一。实验证实了趋化作用基因之间的翻译偶联，并且这些基因的偶联表达被证明可以改善趋化作用。生物信息学分析进一步表明，大肠杆菌的基因顺序与已测序细菌基因组中的共识一致，证实了为降低噪声而进行的进化选择。由于多顺反子基因组织在细菌中很常见，相邻基因之间的翻译偶联可能提供一种普遍机制来增强其信号和代谢网络的稳健性。此外，真核生物中也存在相邻基因表达之间的偶联，因此类似的噪声降低原理可能适用于所有细胞网络。
