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首页> 美国卫生研究院文献>Genome Biology and Evolution >Evolutionary Potential of Cis-Regulatory Mutations to Cause Rapid Changes in Transcription Factor Binding
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Evolutionary Potential of Cis-Regulatory Mutations to Cause Rapid Changes in Transcription Factor Binding

机译：顺式调控突变的进化潜能导致转录因子结合的快速变化

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Transcriptional regulation is crucial for all biological processes and well investigated at the molecular level for a wide range of organisms. However, it is quite unclear how innovations, such as the activity of a novel regulatory element, evolve. In the case of transcription factor (TF) binding, both a novel TF and a novel-binding site would need to evolve concertedly. Since promiscuous functions have recently been identified as important intermediate steps in creating novel specific functions in many areas such as enzyme evolution and protein–protein interactions, we ask here how promiscuous binding of TFs to TF-binding sites (TFBSs) affects the robustness and evolvability of this tightly regulated system. Specifically, we investigate the binding behavior of several hundred TFs from different species at unprecedented breadth. Our results illustrate multiple aspects of TF-binding interactions, ranging from correlations between the strength of the interaction bond and specificity, to preferences regarding TFBS nucleotide composition in relation to both domains and binding specificity. We identified a subset of high A/T binding motifs. Motifs in this subset had many functionally neutral one-error mutants, and were bound by multiple different binding domains. Our results indicate that, especially for some TF–TFBS associations, low binding specificity confers high degrees of evolvability, that is that few mutations facilitate rapid changes in transcriptional regulation, in particular for large and old TF families. In this study we identify binding motifs exhibiting behavior indicating high evolutionary potential for innovations in transcriptional regulation.
机译：转录调节对于所有生物过程都是至关重要的，并且已经在分子水平上针对广泛的生物进行了深入研究。但是，目前还不清楚创新如何发展，例如新型监管要素的活动。在转录因子（TF）结合的情况下，新的TF和新的结合位点都需要协调一致地进化。由于最近发现混杂功能是在许多领域（例如酶进化和蛋白质-蛋白质相互作用）中创建新的特定功能的重要中间步骤，因此我们在此询问TF与TF结合位点（TFBS）的混杂结合如何影响鲁棒性和可进化性严格监管的制度具体来说，我们调查了来自不同物种的数百种TF在前所未有的广度下的结合行为。我们的结果说明了TF结合相互作用的多个方面，范围从相互作用键的强度和特异性之间的相关性，到关于与结构域和结合特异性有关的TFBS核苷酸组成的偏好。我们确定了高A / T绑定基序的子集。该子集中的基序具有许多功能中性的一错误突变体，并被多个不同的结合域结合。我们的结果表明，特别是对于某些TF-TFBS关联，低的结合特异性赋予了高度的进化性，即很少有突变会促进转录调控的快速变化，特别是对于大的和老的TF家族。在这项研究中，我们确定了表现出行为的结合基序，这些行为表明在转录调控方面的创新具有很高的进化潜力。

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