Reconstructing the evolution of novel developmental regulators

进化过程的核心谜团之一是，新的生物特征是如何从缺乏这些特征的祖先中出现的。在最近的动植物进化史上，繁殖的转变是最引人注目的变化之一。在线虫中，自我可育的两性线虫通过获得有限的精子发生而反复从雌性祖先进化而来。这一新颖性是进化发育生物学研究的一个吸引人的主题。它涉及单个组织的细胞的二元命运变化(从卵子到精子)，即生殖系。在动物中发现了生殖细胞，这使得在这里学到的经验可能会产生更广泛的影响。自我繁殖也值得研究，因为它的出现从根本上改变了群体遗传学和性选择的动态，带来了许多潜在的下游后果。这个项目研究了使两个不同物种自我繁殖的基因和蛋白质的变化。通过综合分子生物学、发育遗传学和进化论，这项研究的一个影响是使用比较方法识别新的分子机制。该项目也是一个很好的跨学科科学培训平台。这既包括研究实习生在不同职业阶段的持续工作，也包括与教师和转学学生的较短互动。几条证据表明，一种名为FOG-2的基因的进化是线虫两性人进化的关键一步。它只在线虫中发现，通过突变使其失活，将XX性别恢复为功能正常的雌性，必须像它的祖先一样，通过异种繁殖。之前的研究发现，FOG-2蛋白与一种古老的RNA结合蛋白GLD-1一起工作，以降低关键的促进女性基因tra-2的活性。然而，GLD-1还调控着数百个其他基因，它的缺失会产生一系列复杂的异常，而不仅仅限于性别决定。因此，一个长期存在的谜团是，为什么雾-2的消失只会影响性别决定。最近的研究表明，FOG-2的性别特异性是由于FOG-2和新形成的TRA-2蛋白之间的一种以前未知的相互作用。另一种自我繁殖的物种--布里奇萨毛虫，也依赖于最近进化出的一种F-box蛋白(SHE-1)。然而，SHE-1不与桥链球菌GLD-1相互作用，也不与CBR-TRA-2相互作用。随着XX精子发生在线虫和桥线虫中趋同地进化，性适应似乎在遗传上是灵活的。该项目的核心科学目标是重建使FOG-2和SHE-1从相关的F-box蛋白大家族中脱颖而出的步骤，成为它们今天两性发育的基本调节因素。这一奖项反映了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。

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.