Friedlander Tamar, Prizak Roshan, Barton Nicholas H, Tkačik Gašper
Institute of Science and Technology Austria, Am Campus 1, A-3400, Klosterneuburg, Austria.
The Robert H. Smith Institute of Plant Sciences and Genetics in Agriculture, Faculty of Agriculture Hebrew University of Jerusalem, P.O. Box 12, Rehovot, 7610001, Israel.
Nat Commun. 2017 Aug 9;8(1):216. doi: 10.1038/s41467-017-00238-8.
Gene expression is controlled by networks of regulatory proteins that interact specifically with external signals and DNA regulatory sequences. These interactions force the network components to co-evolve so as to continually maintain function. Yet, existing models of evolution mostly focus on isolated genetic elements. In contrast, we study the essential process by which regulatory networks grow: the duplication and subsequent specialization of network components. We synthesize a biophysical model of molecular interactions with the evolutionary framework to find the conditions and pathways by which new regulatory functions emerge. We show that specialization of new network components is usually slow, but can be drastically accelerated in the presence of regulatory crosstalk and mutations that promote promiscuous interactions between network components.Gene networks evolve by transcription factor (TF) duplication and divergence of their binding site specificities, but little is known about the global constraints at play. Here, the authors study the coevolution of TFs and binding sites using a biophysical-evolutionary approach, and show that the emerging complex fitness landscapes strongly influence regulatory evolution with a role for crosstalk.
基因表达受调控蛋白网络的控制，这些调控蛋白与外部信号和DNA调控序列特异性相互作用。这些相互作用促使网络组件共同进化，从而持续维持功能。然而，现有的进化模型大多关注孤立的遗传元件。相比之下，我们研究调控网络生长的关键过程：网络组件的复制及随后的特化。我们将分子相互作用的生物物理模型与进化框架相结合，以找出新调控功能出现的条件和途径。我们表明，新网络组件的特化通常很缓慢，但在存在调控串扰和促进网络组件间混杂相互作用的突变时，特化过程可被大幅加速。基因网络通过转录因子（TF）的复制及其结合位点特异性的分化而进化，但对于其中起作用的全局限制却知之甚少。在此，作者们使用生物物理-进化方法研究了转录因子与结合位点的共同进化，并表明新出现的复杂适应度景观通过串扰作用对调控进化产生强烈影响。
