Evolution of a Combinatorial Transcriptional Circuit: A Case Study in Yeasts

Book excerpt: Developing new regulation of existing genes is a major source of evolutionary novelty. In this thesis, I examine evolution of transcriptional regulation by dissecting a combinatorial regulatory circuit that governs mating-type in the ascomycete branch of the fungal lineage. I first determine the means by which four conserved transcription factors regulate mating-type in the pathogenic yeast C. albicans. I then closely compare the C. albicans circuit to that of S. cerevisiae, identifying several classes of changes that have arisen since their divergence from a common ancestor. Among the many changes identified, I focus on a group of orthologs, the a-specific genes, that is positively regulated in C. albicans, but is negatively regulated in S. cerevisiae. I demonstrate that positive regulation represents the ancestral form, and that the S. cerevisiae mode of negative regulation is a recently derived innovation. By examining the regulation of asgs in a group of 16 modern yeasts that diverged at successively later times from a common ancestor, I deduce specific, sequential changes in both cis- and trans-regulatory elements that constitute the transition from positive to negative regulation.