Evolution of the Transcriptional Vocabulary

转录词汇的演变

• 批准号: 1518060
• 负责人: Michael Lynch
• 金额: $ 102.88万
• 依托单位: Indiana University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2018-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1518060&HistoricalAwards=false
• 关键词: Evolution; Transcriptional; Vocabulary

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.

该项目将结合分子和计算生物学，以研究基因表达多样性的演变。 在所有生物体中，基因表达均通过称为转录因子的蛋白质和DNA中的特定小区域之间的串扰来控制或调节，这些蛋白质结合了转录因子（转录因子结合位点）。了解这种串扰的关键是学习“调节性词汇”的确切性质。 该项目将着重于在单细胞原生动物Pragecium的多种物种中解密调节语言，这是细胞生物学中建立的模型系统。整个项目将推进对本科生，研究生和博士后研究员的正式培训，同时还为国际研究界建立了一组分子资源。正在做出具体的努力，将所有基因组和基因表达结果整合到Web存储库中，该结果将使用户很容易查询数据中的数十种甲状腺丙烷物种，以获取有关所有已知基因的状态和进化史的信息。该项目的科学和培训结果将有助于促进进化细胞生物学领域的增长，从而扩大我们对生命之树细胞功能多样性的理解。生物多样性的含义归功于其基因重复和基因调节模式的修饰。 黑兆系统非常适合研究基因重复的影响，因为该属的演变包括两个完整的基因组重复，这些重复导致建立了远距离相关但几乎形态上相同的物种的进化枝。这种情况引起了广泛的兴趣，因为还认为两轮基因组重复是在主要脊椎动物谱系的出现和多样化之前。现在，对于大多数甲虫物种，现在都可以使用完整的序列，并且每个基因的进化史已知，下一个目标是确定负责差异基因表达的细胞机制以及与差异基因存活相关的进化机制。使用一组有效的方法来发现转录因子结合位点，该项目将阐明基因调节词汇的进化历史，这些历史是在阿拉比属的十亿年历史上。在大规模基因重复时，发生或不经历完全基因组重复的谱系的比较将有助于确定进化动力学的变化程度。 Pramecium与动物具有一些关键特征，例如具有转录静音种系基因组以及活跃的体细胞核，都在单个高度复杂的细胞的范围内。因此，这些研究的结果非常易于操纵，可能会阐明其他生物体在实验上无法实验易于处理的调节多样性的演变。