Evolution of Reduced Co-Activator Dependence Led to Target Expansion of a Starvation Response Pathway [Scer RNA-seq]

In S. cerevisiae, the phosphate starvation (PHO) responsive transcription factors Pho4 and Pho2 are jointly required for induction of phosphate response genes and survival in phosphate starvation conditions. In the related human commensal and pathogen C. glabrata, Pho4 is required but Pho2 is dispensable for survival in phosphate-limited conditions and is only partially required for inducing the phosphate response genes. This reduced dependence on Pho2 evolved in C. glabrata and closely related species. Pho4 orthologs that are less dependent on Pho2 induce more genes when introduced into the S. cerevisiae background, and Pho4 in C. glabrata both binds to more sites and induces more genes with expanded functional roles compared to Pho4 in S. cerevisiae. We used RNA-seq to profile the transcriptome of wild type and mutants of Pho4 / Pho2, or Pho4 ortholog swap in S. cerevisiae, to identify genes induced by Pho4 or its orthologs in S. cerevisiae background.在酿酒酵母（S. cerevisiae）中，磷酸盐饥饿（PHO）响应转录因子Pho4与Pho2二者共同为磷酸盐响应基因的诱导表达以及磷酸盐饥饿条件下的细胞存活所必需。在与之亲缘关系相近的人类共生致病菌光滑念珠菌（C. glabrata）中，仅需Pho4即可在磷酸盐限制条件下维持细胞存活，而Pho2并非必需，且仅部分参与磷酸盐响应基因的诱导过程。这种对Pho2依赖性降低的特征，是在光滑念珠菌及其近缘物种中演化而来的。那些对Pho2依赖性更低的Pho4直系同源蛋白，当被引入酿酒酵母背景菌株中时，能够诱导更多基因的表达；且相较于酿酒酵母中的Pho4，光滑念珠菌中的Pho4既能结合更多的基因组位点，诱导更多基因表达，还具备更广泛的功能作用。本研究通过RNA测序（RNA-seq）对酿酒酵母中野生型、Pho4/Pho2突变体以及Pho4同源基因替换菌株的转录组进行分析，以鉴定在酿酒酵母背景下由Pho4及其同源蛋白所诱导表达的基因。