Abstract
When yeast cells detect external amino acids via their permease-like Ssy1 sensor, the cytosolic precursor forms of Stp1 and Stp2 transcription factors are activated by endoproteolytic removal of their N-terminal domains, a reaction catalyzed by the Ssy5 endoprotease. The processed Stp factors then migrate into the nucleus, where they activate transcription of several amino acid permease genes including AGP1. We report here that the STP1 and STP2 genes most likely derive from the whole genome duplication that occurred in a yeast ancestor. Although Stp1 and Stp2 have been considered redundant, we provide evidence that they functionally diverged during evolution. Stp2 is the only factor processed when amino acids are present at low concentration, and the transcriptional activation of AGP1 promoted by Stp2 is moderate. Furthermore, only Stp2 can sustain Agp1-dependent utilization of amino acids at low concentration. In contrast, Stp1 is only processed when amino acids are present at high concentration, and it promotes higher level transcriptional activation of AGP1. Domain swapping experiments show that the N-terminal domains of Stp1 and Stp2 are responsible for these proteins being cleaved at different amino acid concentrations. Last, induction of the DIP5 permease gene by amino acids depends on Stp2 but not Stp1. We propose that post-whole genome duplication co-conservation of the STP1 and STP2 genes was favored by functional divergence of their products, likely conferring to cells an increased ability to adapt to various amino acid supply conditions.