Data from: Gene duplication and co-evolution of G1/S transcription factors specificity in fungi are essential for optimizing cell fitness

Transcriptional regulatory networks play a central role in optimizing cell survival. How DNA binding domains and cis-regulatory DNA binding sequences have co-evolved to allow the expansion of transcriptional networks and how this contributes to cellular fitness remains unclear. Here we experimentally explore how the complex G1/S transcriptional network evolved in the budding yeast Saccharomyces cerevisiae by examining different chimeric transcription factor (TF) complexes. Over 300 G1/S genes are regulated by either one of the two TF complexes, SBF and MBF, which bind to specific DNA binding sequences, SCB and MCB, respectively. Our data suggests that whilst SBF is the likely ancestral regulatory complex, the ancestral DNA binding element is more MCB-like. G1/S network expansion took place by both cis- and trans- co-evolutionary changes in closely related but distinct regulatory sequences. Replacement of the endogenous SBF DNA-binding domain (DBD) with that from more distantly related fungi leads to a contraction of the G1/S network in budding yeast, which also correlates with increased defects in cell growth, cell size, and proliferation. This indicates that expansion of the G1/S network in budding yeast may represent an evolutionary product of selection for cell cycle fitness.

转录调控网络在优化细胞存活过程中发挥核心作用。目前尚不明确DNA结合结构域与顺式调控DNA结合序列如何协同进化以促成转录网络的扩张，以及这一过程如何影响细胞适应性。本研究通过分析不同嵌合转录因子（transcription factor, TF）复合物，实验探究了酿酒酵母（Saccharomyces cerevisiae）中复杂的G1/S转录网络的演化历程。超过300个G1/S期基因受两种转录因子复合物——SBF与MBF——的调控，二者分别结合特异性DNA结合序列SCB与MCB。我们的研究数据表明，尽管SBF大概率是祖先调控复合物，但其祖先DNA结合元件更偏向MCB型序列。G1/S转录网络的扩张通过顺式与反式协同进化改变，在密切相关但存在差异的调控序列中得以实现。将酿酒酵母内源SBF的DNA结合结构域（DNA-binding domain, DBD）替换为亲缘关系更远的真菌的对应结构域后，会导致酿酒酵母的G1/S转录网络收缩，这一现象同时与细胞生长、细胞体积及增殖过程中的缺陷加剧相关。这表明酿酒酵母的G1/S转录网络扩张，或许是细胞周期适应性选择下的进化产物。