Evolutionary Rewiring of a Developmental Gene Regulatory Network

发育基因调控网络的进化重新布线

• 批准号: 1457305
• 负责人: Gregory Wray
• 金额: $ 50万
• 依托单位: Duke University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1457305&HistoricalAwards=false
• 关键词: Evolutionary; Rewiring; Developmental; Gene; Regulatory

This project examines how changes in gene regulation contribute to modifications in key life history traits, such as fecundity, lifespan, and age-specific mortality. Knowing more about how life history traits vary within populations, and how they change over evolutionary time will elucidate fundamental biological processes. The approach involves a detailed analysis of gene interactions during key stages of the life cycle in three species of sea urchins. The experiments involve manipulating the operation of key regulatory genes with known functions during the early phase of the life cycle. The impact of these experimental manipulations will then be assayed using several 'big data' approaches that measure the expression of tens of thousands of genes and thousands of proteins and metabolites during subsequent stages of the life history. These results will reveal how differences in the function of key genes impact the function of other genes, thereby influencing anatomy and health. The broader impacts from this project fall into four areas. First, the novel computational methods for analysis of the very large gene expression datasets will have broad utility for basic and applied research. Second, the large datasets will be made freely available to other researchers who work with the same species. Third, there will be significant contributions to the training young scientists, including undergraduate and graduate students. Finally, this project will extend an innovative educational outreach program to middle school students developed by the PI in partnership with the North Carolina Museum of Science.The objective of this project is to identify evolutionary changes in a well defined gene regulatory network (GRN) that contribute to an ecologically significant shift in developmental mode from planktotrophic (feeding) to lecithotrophic (nonfeeding) larvae in sea urchins. The project is identifing maternal changes underlying GRN activation and egg provisioning, and identify zygotic changes in GRN sub-circuits and assess their impact on larval traits. Changes in the energy content of eggs are essential for the evolution of lecithotrophy. The eggs of H. erythrogramma are larger than those of H. tuberculata and other planktotrophs and are packed with prominent lipid droplets. Interestingly, the amount of vitellogenin (yolk protein) per egg is not elevated, but triglycerides and long chain fatty acids are vastly more abundant. Thus, this project focuses on changes in lipid metabolism that may have contributed to the evolution of lecithotrophy in H. erythrogramma to identify specific metabolites that support lecithotrophic development and to understand how those changes might have evolved.

该项目研究了基因调控的变化如何有助于改变关键的生活史特征，如生殖力，寿命和年龄特异性死亡率。了解更多关于生活史特征如何在种群内变化，以及它们如何随着进化时间而变化，将阐明基本的生物学过程。该方法涉及详细分析基因相互作用的关键阶段的生命周期在三种海胆。这些实验涉及在生命周期的早期阶段操纵具有已知功能的关键调控基因的操作。这些实验操作的影响将使用几种“大数据”方法进行分析，这些方法测量了生命史后续阶段数万个基因和数千种蛋白质和代谢物的表达。这些结果将揭示关键基因功能的差异如何影响其他基因的功能，从而影响解剖学和健康。该项目的更广泛影响分为四个领域。首先，用于分析非常大的基因表达数据集的新计算方法将在基础和应用研究中具有广泛的实用性。其次，大型数据集将免费提供给研究同一物种的其他研究人员。第三，将为培训青年科学家，包括本科生和研究生作出重大贡献。最后，这个项目将扩大创新的教育推广计划，以中学生开发的PI与北卡罗来纳州科学博物馆合作，这个项目的目标是确定一个明确的基因调控网络（GRN）的进化变化，有助于一个生态显着转变的发展模式，从营养（喂养）lecithotrophic（非喂养）的海胆幼虫。该项目是确定潜在的GRN激活和卵子供应的母体变化，并确定GRN子电路的合子变化，并评估其对幼虫性状的影响。 卵能量含量的变化对卵营养的进化是必不可少的。H. erythrogramma比H. tuberculata和其他营养型生物，并充满了突出的脂滴。有趣的是，每个鸡蛋的卵黄蛋白原（蛋黄蛋白）的含量并没有升高，但甘油三酯和长链脂肪酸的含量却大大增加。因此，本项目的重点是在脂质代谢的变化，可能有贡献的进化，卵磷脂在H。红细胞计数，以确定特定的代谢物，支持lecithotrophic发展，并了解这些变化可能已经演变。