Evolution of the Transcriptional Vocabulary

这个项目将结合分子生物学和计算生物学来研究基因表达多样性的进化。在所有生物体中，基因的表达都是由转录因子蛋白质和DNA中结合转录因子的特定小区域（转录因子结合位点）之间的串扰控制或调节的。理解这种串音的关键是了解转录因子结合位点的“调节词汇”的确切性质，这些“调节词汇”在生物体之间可能存在差异。该项目将专注于破译多种单细胞原生动物草履虫的调节语言，这是细胞生物学中一个成熟的模型系统。整个项目将推进本科生、研究生和博士后的正式培养，同时也为国际研究界建立一套分子资源。目前正在努力将所有的基因组和基因表达结果组织和整合到一个网络存储库中，这样用户就可以方便地查询几十种草履虫的数据，以获取所有已知基因的状态和进化史信息。该项目的科学和培训成果将有助于促进进化细胞生物学领域的发展，从而拓宽我们对生命之树中细胞功能多样性的理解。许多生物多样性的起源要归功于基因复制和基因调控模式的改变。草履虫系统非常适合研究基因复制的影响，因为这个属的进化包括两个完整的基因组复制，导致建立了一个远亲但几乎形态相同的物种的分支。这种情况引起了广泛的兴趣，因为两轮基因组复制也被认为先于主要脊椎动物谱系的出现和多样化。随着大多数草履虫物种的完整序列和每个基因的进化史的已知，下一个目标是确定负责差异基因表达的细胞机制和与差异基因存活相关的进化机制。利用一套有效的方法发现转录因子结合位点，本项目将阐明草履虫属数十亿年的基因调控词汇的进化史。对经历过或没有经历过全基因组复制的谱系进行比较，将有助于确定面对大规模基因复制时进化动力学改变的程度。草履虫与动物有一些共同的关键特征，比如拥有一个转录沉默的生殖系基因组和一个活跃的体细胞核，所有这些都在一个高度复杂的细胞内。因此，在草履虫这种特别容易操作的生物中进行的这些研究结果，可能会揭示其他生物在实验上不容易处理的调节多样性的进化。

This project will combine molecular and computational biology to study the evolution of diversity in gene expression. In all organisms, gene expression is controlled, or regulated, by crosstalk between proteins called transcription factors and specific small regions in the DNA that bind the transcription factors (transcription factor binding sites.) A key to understanding this crosstalk is learning the precise nature of the "regulatory vocabulary" of transcription factor binding sites which potentially varies among organisms. This project will focus on deciphering the regulatory language in multiple species of the single-celled protozoan Paramecium, a well-established model system in cell biology. The overall project will advance the formal training of undergraduates, graduate students and postdoctoral fellows, while also establishing a set of molecular resources for the international research community. Specific efforts are being made to organize and integrate all genomic and gene-expression results into a web repository that will allow users to readily query data for dozens of Paramecium species to acquire information about status and evolutionary history of all known genes. The scientific and training results from this project will help promote the growth of the field of evolutionary cell biology, thereby broadening our understanding of the diversity of cellular functions across the Tree of Life.Much of biological diversity owes its origin to gene duplication and modifications in gene regulatory patterns. The Paramecium system is well-suited to studying the impacts of gene duplication because the evolution of this genus included two complete-genome duplications that led to the establishment of a clade of distantly related but nearly morphologically identical species. This situation is of broad interest because two rounds of genome duplication are also thought to have preceded the emergence and diversification of the major vertebrate lineages. With complete sequences now available for most Paramecium species, and the evolutionary history of each gene known, the next goal is to determine the cellular mechanisms responsible for differential gene expression and the evolutionary mechanisms associated with differential gene survival. Using a set of efficient methods for discovering transcription factor binding sites, this project will elucidate the evolutionary history of the gene-regulation vocabulary over the billion-year history of the genus Paramecium. Comparisons among lineages that did or did not undergo complete-genome duplications will help define the extent to which evolutionary dynamics are altered in the face of massive gene duplication. Paramecium shares some key features with animals, such as harboring a transcriptionally silent germline genome as well as an active somatic nucleus, all within the confines of a single, highly complex cell. Thus, results of these studies in the Paramecium, which is exceptionally easy to manipulate, may shed light on the evolution of regulatory diversity in other organisms that are not as experimentally tractable.