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

结构、功能、

• 批准号: 1755379
• 负责人: Eric Haag
• 金额: $ 80万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-11-15 至 2022-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1755379&HistoricalAwards=false
• 关键词: Structure; Function; & Evolution; Novel

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.

生殖方式的转变是最近动植物进化史上最引人注目的事件之一。在小杆蠕虫（线虫）中，自能生殖的雌雄同体通过获得在雌性卵巢中制造精子的能力而从雌性祖先反复进化而来。这种新的发展新奇从根本上改变了基因在种群中的流动方式，大大减少了雄性之间的竞争，并带来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（许多基因在雄性生殖中起作用），并且祖先的生殖特征退化。它检查男性分泌短（mss）基因家族，似乎连接这两个现象。MSS蛋白是小的细胞表面因子，在介导不同雄性精子之间的竞争中具有古老的作用，并且在自交进化时一直丢失。这项研究是对进化中两种相对常见现象的案例研究。一个是简单化和祖先特征的丧失。随着研究的展开，PI将与非正式的科学教育专业人士合作，在两个不同的论坛上向公众介绍这一通常违反直觉的过程。另一个是在生殖中起作用的基因的快速进化。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，这项研究可能最终对医学、农业和人类生育产生影响。来自科学领域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，放松选择，可能是雌雄同体的选择，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功能。四个目标将一起阐明这个有趣的家庭的结构，功能和进化：目标1。描述MSS蛋白的结构-功能关系。MSS蛋白的翻译后修饰将被表征，并且天然等位基因和突变的转基因将被用于推断MSS蛋白的对其功能至关重要的特征。目标二。研究MSS在精子-精子和精子-雌性相互作用中的作用。遗传学、活体染料和活体成像将用于阐明MSS蛋白如何影响精子竞争。还将尝试鉴定可能与MSS相互作用的女性组织和分子因子。目标3。描述雄性不育相关蛋白（MSRP）在自交物种中的生殖作用。MSRP是与MSS结构相似的蛋白质，但在所有小杆线虫中发现，无论交配系统如何。MSRP将从自交物种（自然已经缺乏MSS）中删除，以确定它们是否是正常生育所必需的。目标4。描述雄性不育与交配系统的相互作用。我们将通过使用mss+和mss- C的实验微宇宙来检验这样的假设，即自交物种中mss基因的丢失是由选择驱动的，以实现快速的种群增长。该奖项反映了NSF的法定使命，并被认为是值得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的支持。

项目成果

One Gene Is Not Enough To Explain the Evolution of Homosexuality

一个基因不足以解释同性恋的进化

• DOI: 10.1007/s10508-019-01575-z
• 发表时间: 2021
• 期刊: Archives of Sexual Behavior
• 影响因子: 3.8
• 作者: Haag, Eric S.

Evolution of sex ratio through gene loss

基因丢失导致性别比的演变

• DOI: 10.1073/pnas.1903925116
• 发表时间: 2019
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Yin, Da;Haag, Eric S.
• 通讯作者: Haag, Eric S.

Rudolf A. Raff (1941–2019)

鲁道夫·A·拉夫 (1941 – 2019)

• DOI: 10.1038/s41559-019-0844-z
• 发表时间: 2019
• 期刊: Nature Ecology & Evolution
• 影响因子: 16.8
• 作者: Wray, Gregory A.;Haag, Eric S.
• 通讯作者: Haag, Eric S.