Evolution of GRN for Novelty

GRN 的新颖性演变

• 批准号: 1557431
• 负责人: Veronica Hinman
• 金额: $ 64.9万
• 依托单位: Carnegie-Mellon University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1557431&HistoricalAwards=false
• 关键词: Evolution; GRN; Novelty; Evolution; GRN; Novelty

This proposal seeks to understand how genomes (the total DNA sequences of a creature) evolve to generate diversity in animal shapes. Prior to the analysis of genomes of many animals, it was assumed that animals developed differently because they had different protein-coding genes. It is now realized that even very different animals have similar sets of genes, and it is not the genes themselves, but how they are used during embryonic development, that lead to differences. How those genes are used differently during development is poorly understood, however, and is important for understanding the types of changes in animal shape that can occur during evolution. This proposal takes advantage of a clear example of a set of genes that have evolved a new function, i.e. to make a larval skeleton in the sea urchin, while most echinoderms (the group that includes the sea urchins) make a skeleton only in the adult animal. What changes in gene regulation led to this basic new ability? Many community resources will be generated including DNA sequences that will be shared on publically available databases such as NCBI and Echinobase. This proposal will also train postdoctoral researchers, graduate students, and undergraduates, including those from groups that are traditionally underrepresented in science. The broader public will also be engaged in this research through a series of public lectures in Carnegie Mellon's Osher Lifelong Learning Institute and through outreach programs with local K-12 public schools. The gene regulatory network (GRN) for the development of the sea urchin larval skeleton is very well known. Other out-group echinoderm larvae have no or very reduced larval skeletons, yet all echinoderms make a skeleton after metamorphosis. Prior evidence suggests that the sea urchin larval skeleton was co-opted from the GRN for the formation of this adult skeleton. The first objective of this proposal is to determine the set of genes that have been co-opted from the adult skeletogenic program, and are differently expressed in the sea star mesoderm, which does not form a skeleton. Differential RNA-Seq will be used to screen for potential genes in sea urchin, sea cucumbers, and a sea star. Whole-mount in situ hybridization will be used to determine their spatial location. The next objective is to understand how cis-regulatory modules (CRMs) can function in the new larval context and to understand the function of the subcircuits of the co-opted genes in larval sea urchins. ChIP-Seq will identify CRMs and their associated genes. Functional dissection of CRMs and perturbation of identified target genes that are shared targets will determine how these CRMs can function in both the original and new circuit, and also the types of trans environments, and subcircuit topologies that permit cooption. This work will contribute to an understanding of the plasticity and evolvability of GRNs.

该提案试图了解基因组（生物的总DNA序列）如何发展以产生动物形状的多样性。 在分析许多动物基因组之前，假定动物的发展不同，因为它们具有不同的蛋白质编码基因。 现在已经意识到，即使是非常不同的动物也具有相似的基因集，而不是基因本身，而是在胚胎发育过程中使用它们的方式，从而导致差异。 然而，在发育过程中如何使用这些基因的方式不同，但是对于理解进化过程中可能发生的动物形状变化的类型很重要。 该建议利用了一组已经发展出新功能的基因的明确例子，即在海胆中制造幼虫骨骼，而大多数棘皮动物（包括海胆在内的组）仅在成年动物中才能制造骨骼。 基因调节的哪些变化导致了这种基本的新能力？ 将生成许多社区资源，包括将在NCBI和Echinobase等公开可用数据库上共享的DNA序列。 该建议还将培训博士后研究人员，研究生和本科生，包括传统上科学领域不足的团体的研究人员。 更广泛的公众还将通过卡内基·梅隆（Carnegie Mellon）的Osher终身学习研究所以及与当地K-12公立学校的外展计划，参与这项研究。众所周知，用于开发海胆幼虫骨骼的基因调节网络（GRN）。 其他组外的棘皮动物幼虫没有幼虫骨骼，但所有的棘皮动物都在变形后制成骨骼。 先前的证据表明，海胆幼虫骨骼是从GRN中选择的，以形成该成年骨架。 该提案的第一个目的是确定已从成人骨骼发明程序中选择的基因集，并且在海星中胚层中的表达不同，而海星中胚层没有形成骨骼。 差异RNA-Seq将用于筛选海胆，海参和海星中的潜在基因。 整个原位杂交将用于确定其空间位置。 下一个目标是了解顺式调节模块（CRM）如何在新的幼虫环境中起作用，并了解幼体海胆中配置基因的亚电路的功能。 Chip-Seq将识别CRM及其相关基因。 CRM的功能解剖和共享目标的已识别靶基因的扰动将决定这些CRM在原始和新电路以及反式环境的类型以及允许合作的子电路拓扑中的功能。 这项工作将有助于理解GRN的可塑性和发展性。