Structure, Function, & Evolution of a Novel Sperm Competition Protein

繁殖方式的转变是动植物近代进化史上最引人注目的事件之一。在线虫(线虫)中，自我能育的两性人通过获得在其他雌性卵巢中产生精子的能力，反复从女性祖先进化而来。这种发育的新颖性从根本上改变了基因在种群中流动的方式，并极大地减少了男性与男性之间的竞争，从而产生了许多潜在的下游后果。这个项目的动机是观察到自我繁殖的物种已经失去了数千个基因(其中许多基因在男性生殖中发挥了作用)，以及祖先的生殖特征退化了。它研究了男性分泌短基因(MSS)家族，这些基因似乎将这两种现象联系在一起。MSS蛋白是一种小的细胞表面因子，在调节不同男性精子之间的竞争方面发挥着古老的作用，随着自交的进化，MSS蛋白一直在丢失。这项研究是对进化中两种相对常见的现象的个案研究。其一是祖先特征的简化和丧失。随着研究的展开，PI将与非正式的科学教育专业人员合作，在两个不同的论坛上将这一经常违反直觉的过程带给公众。另一个原因是生殖功能基因的快速进化。由于寄生线虫和人类的精子表面都有类似的快速进化的蛋白质，这项研究可能最终会对医学、农业和人类生育能力产生影响。来自科学方面代表性不足的群体的本科生将参与该项目的研究和教育目标。PI和他的同事们假设，宽松的选择，以及可能的两性偏向比率的选择，促进了自我繁殖物种中以前重要的生殖相关基因的丢失。他们还假设，MSS糖蛋白通过其翻译后碳水化合物修饰与女性组织之间的相互作用发挥作用。四个目的一起将阐明这个有趣的家族的结构、功能和进化：目的1.表征MSS蛋白的结构-功能关系。将描述MSS蛋白的翻译后修饰，并将使用自然等位基因和突变的转基因来推断对其功能至关重要的MSS蛋白的特征。目的2.探讨MSS在精子-精子和精子-雌性相互作用中的作用。遗传学、活性染料和活体成像将被用来阐明MSS蛋白如何影响精子竞争。还将尝试确定可能与MSS相互作用的女性组织和分子因素。目的3.研究MSS相关蛋白(MSRPs)在自交物种中的生殖作用。MSRP在结构上与MSS相似，但在所有线虫中都存在，与交配系统无关。MSRP将从自交物种(自然已经缺乏MSS)中删除，以确定它们是否对正常生育是必要的。目的4.描述MSS适合度与交配系统的相互作用。我们将通过使用MSS+和MSS-C的实验微观世界来测试这一假设，即自交物种中MSS基因的丢失是通过选择快速种群增长来驱动的。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。

Shifts in reproductive mode are among the most striking events in the recent evolutionary history of animals and plants. In Caenorhabditis round worms (nematodes), self-fertile hermaphrodites have repeatedly evolved from female ancestors by acquiring the ability to make sperm in an otherwise female ovary. This developmental novelty radically alters how genes flow through populations, and greatly reduces male-male competition, with many potential downstream consequences. This project is motivated by the observations that self-fertile species have lost thousands of genes (many with roles in male reproduction), and that ancestral reproductive traits are degraded. It examines the male secreted short (mss) gene family, which appear to connect these two phenomena. MSS proteins are small, cell surface factors with an ancient role in mediating competition between sperm of different males, and were consistently lost when selfing evolved. This research serves as a case study for two relatively common phenomena in evolution. One is simplification and loss of ancestral traits. As the research unfolds, the PI will partner with informal science education professionals to bring this often counter-intuitive process to the public in two different forums. The other is the rapid evolution of genes that function in reproduction. As the sperm of both parasitic nematodes and of humans have analogous, fast-evolving proteins on their surface, the research may have eventual implications for medicine, agriculture, and human fertility. Undergraduates from groups underrepresented in science will be involved in the research and educational goals of the project. The PI and his colleagues hypothesize that relaxed selection, and possibly selection for a hermaphrodite-biased ratio, promote the loss of formerly important reproduction-related genes in self-fertile species. They also hypothesize that the MSS glycoproteins function via interactions between their post-translational carbohydrate modifications and female tissues. Four aims together will clarify the structure, function, and evolution of this intriguing family:Aim 1. Characterize the structure-function relationships of MSS proteins. Post-translational modifications of MSS proteins will be characterized, and both natural alleles and mutated transgenes will be used to infer the features of MSS proteins that are essential for their function. Aim 2. Investigate the role of MSS in sperm-sperm and sperm-female interactions. Genetics, vital dyes, and live imaging will be used to clarify how MSS proteins influence sperm competition. Attempts will also be made to identify female tissues and molecular factors that may interact with MSS. Aim 3. Characterize reproductive roles of MSS-related proteins (MSRPs) in selfing species. MSRPs are structurally similar proteins to MSS, but are found in all Caenorhabditis, regardless of mating system. MSRPs will be deleted from selfing species (which naturally already lack MSS) to determine whether they are necessary for normal fertility. Aim 4. Characterize how mss fitness interacts with mating system. We will test the hypothesis that loss of mss genes in selfing species is driven by selection for rapid population growth through experimental microcosms employing mss+ and mss- C. briggsae.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.