Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
G3 (Bethesda). 2021 Feb 9;11(2). doi: 10.1093/g3journal/jkab016.
Gene regulatory variations accumulate during evolution and alter gene expression. While the importance of expression variation in phenotypic evolution is well established, the molecular basis remains largely unknown. Here, we examine two closely related yeast species, Saccharomyces cerevisiae and Saccharomyces paradoxus, which show phenotypical differences in morphology and cell cycle progression when grown in the same environment. By profiling the cell cycle transcriptome and binding of key transcription factors (TFs) in the two species and their hybrid, we show that changes in expression levels and dynamics of oscillating genes are dominated by upstream trans-variations. We find that multiple cell cycle regulators show both cis- and trans-regulatory variations, which alters their expression in favor of the different cell cycle phenotypes. Moreover, we show that variations in the cell cycle TFs, Fkh1, and Fkh2 affect both the expression of target genes, and the binding specificity of an interacting TF, Ace2. Our study reveals how multiple variations accumulate and propagate through the gene regulatory network, alter TFs binding, contributing to phenotypic changes in cell cycle progression.
基因调控变异在进化过程中积累，并改变基因表达。虽然表达变异在表型进化中的重要性已得到充分证实，但分子基础在很大程度上仍不清楚。在这里，我们研究了两种密切相关的酵母物种，酿酒酵母和毕赤酵母，它们在相同环境中生长时表现出形态和细胞周期进程的表型差异。通过对两种酵母及其杂种的细胞周期转录组和关键转录因子 (TF) 的结合进行分析，我们表明振荡基因的表达水平和动态变化主要由上游跨变异主导。我们发现多个细胞周期调控因子既表现出顺式调节变异，也表现出反式调节变异，这会改变它们的表达，有利于不同的细胞周期表型。此外，我们还发现细胞周期 TFs（Fkh1 和 Fkh2）的变异会影响靶基因的表达以及相互作用的 TF（Ace2）的结合特异性。我们的研究揭示了多种变异如何在基因调控网络中积累和传播，改变 TF 结合，从而导致细胞周期进程表型变化。
