Evolution of a developmental gene regulatory network during a life history switch in Heliocidaris

多细胞生物表现出惊人的生活史策略的多样性，包括广泛的寿命、第一次繁殖的时间、一生的繁殖力和母体投资。生活史特征通常独立于成虫形态而进化，并对生物体如何相互作用和适应环境产生重大影响。动物生活史上一个特别引人注目的变化是胚胎发育加速，这在包括高度捕食和有限资源在内的各种条件下都是有利的。一套成熟的理论为这些生活史上的变化提供了洞察力，但人们对这些变化是如何演变的知之甚少。这个项目的中心目标是确定在生活史的实质性转变过程中特定特征变化的遗传和分子基础。该研究系统是一组海胆物种，它们的生活史特征非常接近，但却高度不同，包括繁殖力、幼体形态和早期发育速度的显著差异。该项目使用尖端技术，包括表观遗传分析、单细胞测序和基因组编辑，以确定导致一系列生活史特征的基因功能变化。这些研究将提供对生活史和发育机制如何演变的基本见解。了解分子机制的改变如何影响性状和适应，是在医学、农业和生物技术中有重要应用的基础科学。生活史性状是生物多样性的主要组成部分，构成多细胞生物体适应的基本集合，但它们的发育和遗传基础仍然知之甚少，特别是在形态学和生理学方面。该项目旨在确定在海胆属中产生戏剧性生活史转变的基因组和发育机制的变化，即从浮游到营养(小卵子，高繁殖力，摄食幼虫)和卵磷脂营养(大卵子，低繁殖力，不取食幼虫)。该属非常适合于解决激发动机的问题，因为它包含了尽管系统发育关系非常近但生活史截然不同的物种，并且因为海胆的祖先发育基因调控网络(GRN)已经被详细描述。该项目的目标是了解在进化过程中早期发育的关键分子机制是如何改变的，以加速卵磷脂的预变性，以及它们如何在不干扰其他特征的情况下做到这一点。这些目标将通过以下方式实现：全面描述发育过程中的调控状态，以确定在卵磷脂营养起源期间被保守或改变的候选调控分子和相互作用；通过实验干扰候选蛋白质(GRN中的节点)以了解它们的发育功能、可能的交互作用以及对卵磷脂营养起源的贡献；以及识别和干扰可能调节改变相互作用的候选基因调控元件(GRN中的边缘)，以了解它们的分子功能和对卵巢营养不良起源的贡献。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Multicellular organisms exhibit an astonishing diversity of life history strategies, including a wide range of lifespan, time to first reproduction, lifetime fecundity, and maternal investment. Life history traits often evolve independently of adult morphology and are a major influence on how organisms interact with each other and adapt to their environment. A particularly striking life history change in animals is accelerated embryonic development, which is favored under a variety of conditions including high predation and limited resources. A mature body of theory provides insights into why such changes in life histories evolve, but far less is known about how. The central objective of this project is to identify the genetic and molecular basis for changes in specific traits during a substantive shift in life history. The study system is a group of sea urchin species that are very closely related yet highly divergent in terms of life history traits, including striking differences in fecundity, larval form, and rate of early development. This project uses cutting-edge technologies, including epigenetic assays, single-cell sequencing, and genome editing to identify changes in gene function that contributed to a suite of life history traits. These studies will provide basic insights into how life histories and developmental mechanisms evolve. Understanding how alterations in molecular mechanisms contribute to traits and to adaptation is fundamental science that has important applications in medicine, agriculture, and biotechnology.Life history traits are a major component of biological diversity and constitute a fundamental set of adaptations in multicellular organisms, but their developmental and genetic basis remains poorly understood, particularly in relation to morphology and physiology. This project seeks to identify changes in the genome and in developmental mechanisms that produced a dramatic life history transformation within the sea urchin genus Heliocidaris, namely from planktotrophy (small eggs, high fecundity, feeding larvae) and lecithotrophy (large eggs, low fecundity, nonfeeding larvae). This genus is well suited to addressing the motivating questions because it contains species with dramatically divergent life histories despite very close phylogenetic relationships, and because the ancestral developmental gene regulatory network (GRN) of sea urchins has been characterized in detail. The goals of the project are to learn how critical molecular mechanisms of early development were altered during the course of evolution so as to accelerate premetamorphic the lecithotroph, and how they did so without perturbing other traits. These goals will be achieved by comprehensively characterizing regulatory states during development to identify candidate regulatory molecules and interactions that have been conserved or altered during the origin of lecithotrophy; experimentally perturbing candidate proteins (nodes in the GRN) to learn about their developmental function, likely interactors, and contributions to the origin of lecithotrophy; and identifying and perturbing candidate gene regulatory elements that may mediate altered interactions (edges in the GRN) to understand their molecular function and contributions to the origin of lecithotrophy.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.