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.

生殖模式的变化是最近动物和植物进化史上最引人注目的事件之一。在Caenorhabditis圆形蠕虫（线虫）中，通过获得在原本女性卵巢中制作精子的能力，可以从女性祖先中反复演变自雌雄同体。这种发展的新颖性从根本上改变了基因流入人群的流动，并大大减少了男性竞争，并带来了许多潜在的下游后果。该项目的动机是由观察到自我硬脂物种损失了数千个基因（许多在男性繁殖中的作用），并且祖先的生殖特征被降解。它检查了男性分泌的短（MSS）基因家族，这似乎连接了这两种现象。 MSS蛋白很小，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，并且在自我发展时会持续失去。这项研究是对进化中两个相对常见现象的案例研究。一种是简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员合作，将这一经常违反直觉的过程在两个不同的论坛中向公众带给公众。另一个是在繁殖中起作用的基因的快速演变。由于寄生线虫和人类的精子在其表面上都具有类似的，快速发展的蛋白质，因此该研究可能对医学，农业和人类的生育具有最终影响。来自科学领域不足的小组的本科生将参与该项目的研究和教育目标。 PI和他的同事假设选择了轻松的选择，并可能选择了雌雄同体偏置的比例，可以促进自肥物种中以前重要的繁殖相关基因的丧失。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。四个目标将阐明这个有趣的家庭的结构，功能和演变：目标1。表征MSS蛋白的结构功能关系。 MSS蛋白的翻译后修饰将被表征，并且将使用天然等位基因和突变的转基因来推断MSS蛋白的特征，这对于其功能至关重要。 AIM 2。研究MSS在精子和精子女性相互作用中的作用。遗传学，重要染料和实时成像将用于阐明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素。 AIM 3。表征MSS相关蛋白（MSRP）在自我物种中的生殖作用。 MSRP在结构上与MSS相似，但在所有Caenorhabditis中都发现，无论交配系统如何。 MSRP将从自变化物种（自然已经缺乏MS）中删除，以确定它们是否需要正常生育能力。 AIM 4。表征MSS健身与交配系统相互作用的方式。我们将检验以下假设：自我物种中MSS基因的丧失是由通过使用MSS+和MSS-C。Briggsae的实验缩影选择快速人口增长的。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的智力功能和更广泛影响的评估来通过评估来支持的，这是值得的。

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.

Still Searching for Specialized Ribosomes

• DOI: 10.1016/j.devcel.2019.03.005
• 发表时间: 2019-03-25
• 期刊: DEVELOPMENTAL CELL
• 影响因子: 11.8
• 作者: Haag, Eric S.;Dinman, Jonathan D.
• 通讯作者: Dinman, Jonathan D.

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.