Evolutionary Transition of GAL Regulatory Circuit from Generalist to Specialist Function in Ascomycetes

The Gal4 transcription factor (TF) controls gene expression by binding the DNA sequence motif CGG(N₁₁)CCG. Well studied versions regulate metabolism of glucose in Candida albicans and galactose in Saccharomyces cerevisiae. Gal4 is also found within Aspergillus species and shows a wide range of potential binding targets. Members of the CTG clade that reassigned CUG codons from leucine to serine lack the Gal80 binding domain of Gal4, and they use the TF to regulate only glycolytic genes. In this clade, the galactose catabolic pathway (also known as the Leloir pathway) genes are regulated by Rtg1/Rtg3. In the WGD species, the complete Gal4/Gal80 module is limited to regulation of the Leloir pathway, while glycolysis is controlled by Gcr1/Gcr2. This shows a switch of Gal4 from a generalist to a specialist within the ascomycetes, and the split of glucose and galactose metabolism into distinct regulatory circuits.