Transfer of noncoding DNA drives regulatory rewiring in bacteria
Transfer of noncoding DNA drives regulatory rewiring in bacteria
复制标题
DOI：
10.1073/pnas.1413272111
复制
发表时间：
2014-11-11
影响因子：
11.1
通讯作者：
Pupko, Tal
中科院分区：
文献类型：
--
作者：
Oren, Yaara;Smith, Mark B.;Pupko, Tal
了解产生变异的机制是统一生命科学的共同追求。细菌是一个特别令人震惊的难题，因为密切相关的菌株具有完全不同的代谢和生态能力。基因转移引起的蛋白质组差异目前被认为是细菌表型可塑性的主要机制。虽然细菌编码可塑性在过去的几十年中已经得到了广泛的研究，但对调控可塑性在细菌进化中所起的作用知之甚少。在这里，我们表明，细菌基因可以通过获得功能上不同的非同源启动子区域，在多种调控模式之间迅速转变。通过对247个基因组中的270，000个调控区域的分析，我们证明了向非同源替代物的调控“切换”是普遍存在的，发生在整个细菌结构域中。使用比较转录组学，我们表明，至少有16%的大肠杆菌菌株之间的表达差异可以解释这种监管开关。此外，使用寡核苷酸调控文库，我们建立开关影响细菌启动子结构。我们提供的证据表明，调控开关可以通过水平调控转移发生，这使得调控区域跨菌株，甚至属，独立于他们调节的基因。最后，通过实验表征了调节转移对致病性大肠杆菌的适应性效应。大肠杆菌菌株，我们证明了调节开关elevant重要的表型后果。总之，我们的研究结果揭示了细菌中以前未被重视的调节可塑性，并为理解细菌表型变异和适应提供了一个途径。
Understanding the mechanisms that generate variation is a common pursuit unifying the life sciences. Bacteria represent an especially striking puzzle, because closely related strains possess radically different metabolic and ecological capabilities. Differences in protein repertoire arising from gene transfer are currently considered the primary mechanism underlying phenotypic plasticity in bacteria. Although bacterial coding plasticity has been extensively studied in previous decades, little is known about the role that regulatory plasticity plays in bacterial evolution. Here, we show that bacterial genes can rapidly shift between multiple regulatory modes by acquiring functionally divergent nonhomologous promoter regions. Through analysis of 270,000 regulatory regions across 247 genomes, we demonstrate that regulatory "switching" to nonhomologous alternatives is ubiquitous, occurring across the bacterial domain. Using comparative transcriptomics, we show that at least 16% of the expression divergence between Escherichia coli strains can be explained by this regulatory switching. Further, using an oligonucleotide regulatory library, we establish that switching affects bacterial promoter architecture. We provide evidence that regulatory switching can occur through horizontal regulatory transfer, which allows regulatory regions to move across strains, and even genera, independently from the genes they regulate. Finally, by experimentally characterizing the fitness effect of a regulatory transfer on a pathogenic E. coli strain, we demonstrate that regulatory switching elicits important phenotypic consequences. Taken together, our findings expose previously unappreciated regulatory plasticity in bacteria and provide a gateway for understanding bacterial phenotypic variation and adaptation.