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，新的生物特征是如何从缺乏这些特征的祖先身上出现的。繁殖的转变是最近动物和植物进化史上最引人注目的变化之一。在小杆线虫中，通过获得有限的精子发生，自能生殖的雌雄同体重复地从雌性祖先进化而来。这种新奇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（生殖系）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有发现，这使得这里学到的教训可能具有更广泛的意义。自育性也值得研究，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。该项目研究了基因和蛋白质的变化，这些变化使两个不同物种能够自我繁殖。通过综合分子生物学，发育遗传学和进化，这项研究的一个影响是使用比较方法识别新的分子机制。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不同职业阶段的持续工作，也包括与教师和转校生的较短互动。几条证据表明，一种名为fog-2的基因的进化是C。雌雄同体它只在C中找到。它的失活突变恢复XX性别的功能女性，必须异交繁殖，像它的祖先。先前的研究发现，FOG-2蛋白与一种古老的RNA结合蛋白GLD-1一起作用，降低了一种关键的女性促进基因tra-2的活性。然而，GLD-1还调节着数百个其他基因，它的缺失会产生一系列复杂的异常，不仅限于性别决定。因此，一个长期存在的谜团是为什么FOG-2的丢失只影响性别决定。最近的研究表明，FOG-2对性别的特异性是由于FOG-2和新形成的TRA-2蛋白之间以前未被认识到的相互作用。第二个自交能育的种C. Briggsae也依赖于最近进化的F-box蛋白（SHE-1）。然而，SHE-1不与C相互作用。Briggsae GLD-1，也不与Cbr-TRA-2。随着XX的出现，C.和秀丽隐杆线虫C.布里格塞说，性适应似乎是基因上灵活的。该项目的核心科学目标是重建FOG-2和SHE-1从一个相关的F-box蛋白大家族中脱颖而出的步骤，成为今天雌雄同体发育的重要调节因子。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。