Evolution of major metabolic regulatory circuits in the fungal lineage. The conservation of a regulatory motif in the ascomycetes lineage is depicted as a colored bar. The enrichment of TF-binding sites in each metabolic function in each species was tested with a hypergeometric distribution and a simplified representation of the data was created. (a–d) Heatmap display of various transcription factor-binding motifs in seven functional categories. Orthologous gene sets involved in phospholipid biosynthesis (Lipid), beta-oxidation and peroxisome (Perox), galactolysis (Galacto), glycolysis (Glyco), tRNA-aminoacyl-transfer (tRNA), amino-acid biosynthesis (AA) and nucleolar genes (Nucleolus) from 15 completely sequenced fungal genomes were tested for enrichment of the Ctf1, Ino4, Gal4, GalX, Gcn4 and PAC-Pbf1/2 motifs. Color saturation follows log₁₀ enrichment p-values given by the hypergeometric distribution starting with faint color (p = 10⁻²) to saturation (p = 10E⁻⁶). (e) Transcription factors involved in the rewiring of the different biological functions reviewed here.

Evolution of transcription factor connections with metabolic sensors and intracellular cellular signaling. (a) Reorganization of the galactose-sensing co-regulators and their co-evolution with the Gal4 DNA-binding transcription factor. (b) The translational control of the GCN4 mRNA is highly stringent in S. cerevisiae and depends on the eIF2α kinase Gcn2. This post-transcriptional mechanism of Gcn4 regulation seems to have been lost in C. albicans. (c) The ribosomal transcriptional regulatory complex is connected to TOR and PKA signaling through the Fhl1-Ifh1 heterodimer in both S. cerevisiae and C. albicans even though the central DNA-binding regulators have been exchanged between species.

Reutilization of regulatory switches in C. albicans and S. cerevisiae. Possible scenarios of evolutionary tinkering with transcriptional regulatory switches in ascomycetes connecting related biological processes situated within the lipid (green), hexose (cyan), amino acid (red) and protein synthesis (orange) ‘regulatory fields’.