School of Computer Science and Engineering, Hebrew University, Jerusalem, Israel.
Mol Syst Biol. 2012;8:619. doi: 10.1038/msb.2012.50.
Evolutionary rewiring of regulatory networks is an important source of diversity among species. Previous evidence suggested substantial divergence of regulatory networks across species. However, systematically assessing the extent of this plasticity and its functional implications has been challenging due to limited experimental data and the noisy nature of computational predictions. Here, we introduce a novel approach to study cis-regulatory evolution, and use it to trace the regulatory history of 88 DNA motifs of transcription factors across 23 Ascomycota fungi. While motifs are conserved, we find a pervasive gain and loss in the regulation of their target genes. Despite this turnover, the biological processes associated with a motif are generally conserved. We explain these trends using a model with a strong selection to conserve the overall function of a transcription factor, and a much weaker selection over the specific genes it targets. The model also accounts for the turnover of bound targets measured experimentally across species in yeasts and mammals. Thus, selective pressures on regulatory networks mostly tolerate local rewiring, and may allow for subtle fine-tuning of gene regulation during evolution.
调控网络的进化重连是物种多样性的一个重要来源。先前的证据表明，调控网络在物种间存在显著的分歧。然而，由于实验数据有限和计算预测的噪声性质，系统评估这种可塑性的程度及其功能意义一直具有挑战性。在这里，我们引入了一种研究顺式调控进化的新方法，并利用它来追踪 23 种子囊菌真菌中 88 个转录因子 DNA 基序的调控历史。虽然基序是保守的，但我们发现它们对靶基因的调控普遍存在增益和损失。尽管存在这种更替，但与基序相关的生物学过程通常是保守的。我们使用一个模型来解释这些趋势，该模型对转录因子的整体功能有很强的保守选择，而对其靶向的特定基因的选择则较弱。该模型还解释了在酵母和哺乳动物中跨物种测量的结合靶标的周转率。因此，对调控网络的选择压力大多容忍局部重连，并可能允许在进化过程中对基因调控进行微妙的微调。
