Transcriptional rewiring generates phenotypic novelty, acting as an important mechanism contributing to evolutionary development, speciation, and adaptation in all organisms. The phenotypic outcomes (functions) of transcription factor (TF) activity are determined by the combined effects of all target genes in the TF’s regulatory network. Plastic rewiring of target genes accumulates during species divergence and ultimately alters phenotypes, indicating a TF functional switch. We define this phenomenon as ‘disruptive rewiring’, where the rewiring process disrupts the link between a TF and its original target genes that determine phenotypes. Here, we investigate if ‘complete’ disruptive rewiring is a prerequisite for a TF functional switch by employing chromatin immunoprecipitation sequencing, RNA expression, and phenotypic assays across yeast species. In yeasts where Sef1 targets TCA (tricarboxylic acid) cycle genes, we demonstrate that Sef1 orthologs can promote and inhibit respiratory growth by modulating the moonlighting function of their conserved target, NDE1. This modulation occurs without changing the overall association of Sef1 with TCA cycle genes. We propose that phenotypic masking by NDE1 promotes ‘deceptive’ disruptive rewiring of the Sef1 regulatory network in Saccharomyces cerevisiae, thereby potentially constraining future evolutionary trajectories.

中文翻译：

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靶基因的蛋白质兼职主导了酵母中 Sef1 转录调控网络的表型分歧


转录重连接产生表型新颖性，是促进所有生物体进化发育、物种形成和适应的重要机制。转录因子 （TF） 活性的表型结果（功能）由 TF 调节网络中所有靶基因的综合效应决定。靶基因的塑料重新布线在物种分化过程中积累，并最终改变表型，表明 TF 功能转换。我们将这种现象定义为“破坏性重新布线”，其中重新布线过程破坏了 TF 与其决定表型的原始靶基因之间的联系。在这里，我们通过对酵母物种采用染色质免疫沉淀测序、RNA 表达和表型测定来研究“完全”破坏性重新布线是否是 TF 功能转换的先决条件。在 Sef1 靶向 TCA （三羧酸） 循环基因的酵母中，我们证明 Sef1 直系同源物可以通过调节其保守靶标 NDE1 的月光功能来促进和抑制呼吸生长。这种调节的发生不会改变 Sef1 与 TCA 循环基因的整体关联。我们提出 NDE1 的表型掩蔽促进了酿酒酵母中 Sef1 调节网络的“欺骗性”破坏性重新布线，从而可能限制未来的进化轨迹。