Reconstructing the evolution of novel developmental regulators

重建新型发育调节因子的进化

• 批准号: 2308465
• 负责人: Eric Haag
• 金额: $ 100万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2308465&HistoricalAwards=false
• 关键词: Reconstructing; evolution; novel; developmental; regulators

One of the central mysteries of the evolutionary process is how new organismal features emerge from ancestors lacking them. Shifts in reproduction are some of the most striking changes in the recent evolutionary histories of animals and plants. In Caenorhabditis nematodes, self-fertile hermaphrodites have repeatedly evolved from female ancestors by acquiring limited spermatogenesis. This novelty is an appealing subject of evolutionary developmental biology research. It involves a binary fate change (from egg to sperm) in the cells of a single tissue, the germ line. Germ cells are found across animals, making lessons learned here likely to have broader implications. Self-fertility also merits study because its appearance radically alters population genetics and the dynamics of sexual selection, with many potential downstream consequences. This project examines the changes to genes and proteins that enable self-fertility in two different species. By synthesizing molecular biology, developmental genetics, and evolution, one impact of this research is the identification of new molecular mechanisms using a comparative approach. The project is also an excellent platform for training in interdisciplinary science. This includes both the sustained work by research trainees at various career stages, as well as shorter interactions with teachers and transfer students.Several lines of evidence point to the evolution of a gene called fog-2 as a key step in the evolution of the C. elegans hermaphrodite. It is only found in C. elegans, and its inactivation by mutation reverts the XX sex to a functional female that must outcross to reproduce, like its ancestors. Previous research has found that the FOG-2 protein works with an ancient RNA-binding protein, GLD-1, to reduce the activity of a key female-promoting gene, tra-2. However, GLD-1 also regulates hundreds of other genes, and its loss produces a complex set of abnormalities not restricted to sex determination. A long-standing mystery has thus been why loss of FOG-2 only impacts sex determination. Recent studies indicate the specificity of FOG-2 for sex is due to a previously unrecognized interaction between FOG-2 and the newly formed TRA-2 protein. A second self-fertile species, C. briggsae, also relies on a recently evolved F-box protein (SHE-1). However, SHE-1 does not interact with C. briggsae GLD-1, nor with Cbr-TRA-2. As XX spermatogenesis evolved convergently in C. elegans and C. briggsae, sexual adaptation appears to be genetically flexible. The core scientific goal of this project is to reconstruct the steps that allowed FOG-2 and SHE-1 to emerge from a large family of related F-box proteins to become the essential regulators of hermaphrodite development they are today.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.

进化过程的核心奥秘之一是新的有机体特征是如何从缺乏它们的祖先那里出现的。在动物和植物的近代进化史上，繁殖的变化是最引人注目的变化之一。在隐杆线虫中，通过获得有限的精子发生，自育的雌雄同体反复从雌性祖先进化而来。这种新奇的事物是进化发育生物学研究的一个吸引人的主题。它涉及到一个单一组织，即生殖系的细胞的二元命运变化（从卵子到精子）。生殖细胞在动物身上都能找到，这使得我们在这里学到的经验可能具有更广泛的意义。自我生育也值得研究，因为它的出现从根本上改变了种群遗传学和性选择的动态，并带来了许多潜在的下游后果。这个项目研究了两个不同物种的基因和蛋白质的变化，这些基因和蛋白质使它们能够自我生育。通过综合分子生物学、发育遗传学和进化，本研究的一个影响是使用比较方法确定新的分子机制。该项目也是跨学科科学培训的良好平台。这既包括研究受训者在不同职业阶段的持续工作，也包括与老师和转学生的短期互动。几条线索的证据表明，一种名为fog-2的基因的进化是秀丽隐杆线虫雌雄同体进化的关键一步。它只存在于秀丽隐杆线虫中，通过突变使其失活，使XX性别恢复为有功能的雌性，必须像其祖先一样异交才能繁殖。先前的研究发现，fog2蛋白与一种古老的rna结合蛋白GLD-1一起作用，降低了一种关键的雌性促进基因tra-2的活性。然而，GLD-1也调节数百个其他基因，它的缺失会产生一系列复杂的异常，而不仅仅局限于性别决定。因此，一个长期存在的谜团是，为什么失去fog2只会影响性别决定。最近的研究表明，fog2的性别特异性是由于fog2和新形成的TRA-2蛋白之间先前未被认识到的相互作用。另一种自交生殖物种C. briggsae也依赖于最近进化的F-box蛋白（SHE-1）。然而，SHE-1不与C. briggsae GLD-1和Cbr-TRA-2相互作用。由于秀丽隐杆线虫和秀丽隐杆线虫的XX精子发生进化趋同，性适应在遗传上似乎是灵活的。该项目的核心科学目标是重建允许fog2和SHE-1从相关的F-box蛋白大家族中出现的步骤，从而成为雌雄同体发育的重要调节因子。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。