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. Overall design: The goal is to identify genes induced by each of the eight Pho4 orthologs in the S. cerevisiae background, either with or without S. cerevisiae Pho2 (ScPho2) and with the negative regulator of Pho4, Pho80, deleted. Pairwise comparisons such as that between a S. cerevisiae strain carrying Pho4 from C. glabrata (CgPho4) and a pho4? strain, both in the pho80? ScPHO2 background, will identify genes induced by CgPho4 in the presence of ScPho2. For each strain, two biological replicates, i.e. the same genotype grown, collected and processed separately, were analyzed by RNA-seq.

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He BZ, Zhou X, O'Shea EK