Rewiring of Genetic Circuits Regulating Meiosis

当物种进化时，DNA的变化可能导致新的基因功能或现有功能的“重新布线”，即，基因协同工作以实现重要功能的精确方式。这项工作调查了减数分裂的重新布线，这涉及到一个专门的细胞分裂程序，在多个物种的酵母。特别是，一些念珠菌属物种与研究得更好的面包酵母不同，因为减数分裂是由两个物种中的不同基因控制的。 以前的结果表明，蛋白质（Ste 12），这是执行减数分裂无关的功能，在面包酵母，进化到控制减数分裂在至少一个念珠菌属物种。这个项目将研究导致Ste 12功能重新使用的重新布线事件。 该项目将通过在当地高中和大学的学生、教师和教职员工之间建立互动来激发对微生物学和研究的兴趣。这将通过罗得岛学生微生物学学会分会的发展和开发动画微生物学播客等教育工具来实现。将特别鼓励代表性不足的少数民族学生参与这项工作。此外，本研究中研究的许多酵母物种本身与健康和生物技术相关，因此了解它们的生物学具有普遍意义和重要性。该项目将利用比较和功能基因组学来比较多个酵母物种中减数分裂的调节方式。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，这些因子的分子机制将被确定，以及重新布线事件，导致不同的电路配置之间的物种。特别是，Ime 1在几个物种中作为减数分裂的主转录调节因子，而最近的实验发现Ste 12作为其他物种中减数分裂的新调节因子。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确切作用。将确定与Ime 1或Ste 12一起工作并可能促进电路重新布线的潜在辅因子。这些重新布线事件可能赋予的健身优势也将受到测试。总之，这些研究将揭示遗传电路如何通过现有电路的转录重新布线而进化，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.