Rewiring of Genetic Circuits Regulating Meiosis

当物种进化时，DNA的变化可能会导致新的基因功能或现有功能的“重新连接”，即基因协同工作以实现重要功能的确切方式。这项工作研究了跨多种酵母的减数分裂的重新布线，这涉及到一个专门的细胞分裂程序。特别是，一些念珠菌与研究得更好的面包师酵母不同，因为这两个物种的减数分裂是由不同的基因控制的。先前的结果表明，在面包酵母中，一种执行减数分裂无关功能的蛋白质(STE12)进化为控制至少一个念珠菌的减数分裂。本项目将研究导致STE12功能改变用途的重新布线事件。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来激发人们对微生物学和研究的兴趣。这将通过在罗德岛建立学生微生物学协会分会和开发动画微生物学播客等教育工具来实现。将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，这项研究中调查的许多酵母物种本身都与健康和生物技术有关，从而了解它们普遍感兴趣和重要的生物学。该项目将利用比较基因组学和功能基因组学来比较多种酵母物种减数分裂是如何调节的。初步实验已经确定，不同的转录因子调节不同酵母物种的减数分裂，这些因子发挥作用的分子机制将被确定，以及导致不同物种之间不同电路配置的重新连接事件。特别是，Ime1在几个物种中作为减数分裂的主要转录调节因子，而最近的实验发现STE12在其他物种中是一个新的减数分裂调节因子。实验将包括使用ChIP-Seq和RNA-Seq来检查这些主要转录因子在调节减数分裂中的确切作用。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素。这些重新布线活动可能带来的健身优势也将得到测试。总之，这些研究将揭示基因电路是如何通过对现有电路进行转录重新布线来进化的，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.