Rewiring of Genetic Circuits Regulating Meiosis

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When species evolve, DNA changes can result either in new gene functions or the 'rewiring' of existing functions, i.e., the precise way in which genes work together to enable vital functions to be carried out. This work investigates the rewiring of meiosis, which involves a specialized program of cell division, across multiple species of yeast. In particular, some Candida species are different from the better-studied baker`s yeast in that meiosis is controlled by different genes in the two species. Previous results suggest that a protein (Ste12) which is performing meiosis-unrelated functions in baker's yeast, evolved to control meiosis in at least one Candida species. This project will study the rewiring events that led to this repurposing of Ste12 function. The project will stimulate interest in microbiology and research by establishing interactions between students, teachers, and faculty at local high schools and universities. This will be achieved through the growth of a student microbiology society chapter in Rhode Island and by developing educational tools such as animated microbiology podcasts. Students from underrepresented minorities will be particularly encouraged to be involved in this work. In addition, many of the yeast species investigated in this study are themselves relevant to health and biotechnology, making an understanding of their biology of general interest and importance.The project will utilize comparative and functional genomics to compare how meiosis is regulated in multiple yeast species. Preliminary experiments have established that different transcription factors regulate meiosis in different yeast species, and the molecular mechanisms by which these factors work will be determined, as well as the rewiring events that led to different circuit configurations between species. In particular, Ime1 acts as the master transcriptional regulator of meiosis in several species, while recent experiments have uncovered Ste12 as a novel regulator of meiosis in other species. Experiments will include the use of ChIP-Seq and RNA-Seq to examine the precise role of these master transcription factors in regulating meiosis. Potential co-factors that work with Ime1 or Ste12, and may facilitate circuit rewiring, will be determined. The fitness advantages that these rewiring events may confer will also be tested. Together, these studies will reveal how genetic circuits evolve by transcriptional rewiring of existing circuits, and the consequences of these rewiring events for the lifestyle of the species.