Evolution of a combinatorial transcriptional circuit: a case study in yeasts.

Developing new regulation of existing genes is likely a key mechanism by which organismal complexity arises in evolution. To examine plasticity of gene regulation over evolutionary timescales, we have determined the transcriptional circuit regulating mating type in the human fungal pathogen Candida albicans, and compared it to that of Saccharomyces cerevisiae. Since the two yeasts last shared an ancestor 100-800 million years ago, several major differences in circuitry have arisen. For example, a positive regulator of mating type was retained in C. albicans but lost in S. cerevisiae; this circuit branch was replaced by the modification of an existing negative regulator, thereby conserving the circuit output. We also characterize a tier of mating type transcriptional regulation that is present only in C. albicans, and likely results from the vastly different environmental selections imposed on the two yeasts--in this case, the pressure on C. albicans to survive in a mammalian host.