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; 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.

进化过程的中心奥秘之一是祖先缺乏新的有机物特征是如何出现的。繁殖的变化是动物和植物最近进化史上最引人注目的变化。在线虫性炎，在女性祖先中，通过获得有限的精子发生来反复演变出来的雌雄同体。这种新颖性是进化发展生物学研究的吸引人的主题。它涉及单个组织细胞中的细胞中的二元命运变化（从卵到精子）。生殖细胞在跨动物中发现，从而使这里学到的经验教训可能具有更广泛的影响。自我育性也值得研究，因为它的外观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。该项目研究了基因和蛋白质的变化，这些基因和蛋白质能够在两个不同的物种中产生自育。通过综合分子生物学，发育遗传学和进化，这项研究的影响是使用比较方法鉴定新的分子机制。该项目也是跨学科科学培训的绝佳平台。这既包括研究学员在各个职业阶段的持续工作，以及与教师和转学学生的互动较短。几个证据表明，一个名为Fog-2的基因的演变是C. elegrans Hermaphrodite演变的关键一步。它仅在秀丽隐杆线虫中发现，而突变的失活才使XX性别恢复为必须像祖先一样脱落的功能性女性。先前的研究发现，FOG-2蛋白与古老的RNA结合蛋白GLD-1一起使用，以降低关键女性促进基因的活性Tra-2。但是，GLD-1还调节了数百个其他基因，其损失会产生一组复杂的异常，而不仅限于性别确定。因此，长期以来的谜团就是为什么FOG-2损失仅影响性别决定的原因。最近的研究表明，FOG-2对性别的特异性是由于先前无法识别的FOG-2与新形成的Tra-2蛋白之间的相互作用所致。第二种自我肉种的物种也依赖于最近进化的F-box蛋白（SHE-1）。但是，She-1与Briggsae Gld-1不相互作用，也不与CBR-TRA-2相互作用。随着XX的精子发生在秀丽隐杆线虫和briggsae中趋同演变，性适应似乎是遗传柔性的。该项目的核心科学目标是重建允许Fog-2和She-1从大型相关F-box蛋白家族中出现的步骤，以成为他们今天所成为的雌雄同体开发的基本调节者。该奖项反映了NSF的法定任务，并通过使用该基金会的知识优点和广泛的影响来评估NSF的法定任务，并被认为是值得通过评估来支持的。