Rewiring of Genetic Circuits Regulating Meiosis

当物种进化时，DNA的变化要么导致新的基因功能，要么导致现有功能的“重新布线”，即基因协同工作以实现重要功能的精确方式。这项工作研究了减数分裂的重新布线，这涉及到一个特殊的细胞分裂程序，跨多种酵母。特别是，一些念珠菌种类与研究得更好的面包酵母不同，因为减数分裂是由两种不同的基因控制的。先前的研究结果表明，一种在面包酵母中执行减数分裂无关功能的蛋白质（Ste12）进化到控制至少一种念珠菌的减数分裂。该项目将研究导致Ste12功能重新利用的重新布线事件。该项目将通过在当地高中和大学建立学生、教师和教职员工之间的互动，激发人们对微生物学和研究的兴趣。这将通过罗德岛州学生微生物学会分会的发展和开发动画微生物播客等教育工具来实现。特别鼓励来自代表性不足的少数民族的学生参与这项工作。此外，本研究中调查的许多酵母物种本身与健康和生物技术有关，因此了解它们的生物学具有普遍的意义和重要性。该项目将利用比较和功能基因组学来比较多种酵母物种的减数分裂是如何调节的。初步的实验已经确定了不同的转录因子在不同的酵母物种中调控减数分裂，这些因子工作的分子机制将被确定，以及导致物种之间不同电路配置的重新布线事件。特别是，在一些物种中，Ime1是减数分裂的主要转录调控因子，而最近的实验发现Ste12是其他物种减数分裂的新调控因子。实验将包括使用ChIP-Seq和RNA-Seq来检查这些主转录因子在调节减数分裂中的精确作用。将确定与Ime1或Ste12一起工作并可能促进电路重新布线的潜在辅助因子。这些重新布线事件可能带来的适应性优势也将得到检验。总之，这些研究将揭示遗传回路是如何通过现有回路的转录重新布线而进化的，以及这些重新布线事件对物种生活方式的影响。

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.