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，被称为转录因子的蛋白质和DNA中结合转录因子的特定小区域(转录因子结合部位)之间的串扰控制或调节着基因的表达。理解这种串扰的关键是了解转录因子结合位点的“调控词汇”的确切性质，这可能在不同的生物体中有所不同。这个项目将专注于破译单细胞原生动物草履虫的多个物种的调控语言，草履虫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、研究生和博士后研究员的正规培训，同时还将为国际研究界建立一套分子资源。正在作出具体努力，将所有基因组和基因表达结果组织和整合到一个网络储存库中，使用户能够方便地查询数十个草履虫物种的数据，以获得有关所有已知基因的状态和进化历史的信息。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上细胞功能多样性的理解。许多生物多样性的起源是基因复制和基因调控模式的修改。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全基因组复制，这导致了一个远亲但在形态上几乎相同的物种分支的建立。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是在主要脊椎动物谱系出现和多样化之前发生的。随着大多数草履虫物种的完整序列的获得，以及每个基因的进化历史已知，下一个目标是确定导致差异基因表达的细胞机制和与差异基因生存相关的进化机制。使用一套发现转录因子结合位点的有效方法，该项目将阐明草履虫属数十亿年历史中基因调控词汇的进化历史。对进行或没有进行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，进化动态发生了多大程度的改变。草履虫与动物有一些共同的关键特征，例如拥有转录沉默的生殖系基因组以及活跃的体细胞核，所有这些都在单个高度复杂的细胞内。因此，草履虫的这些研究结果非常容易操作，可能会揭示其他生物中调控多样性的进化，这些生物在实验上不是那么容易驯化的。

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.