A Tale of No Tail: Sperm Flagella Loss in Mormyrids

无尾的故事：斑鸠鱼精子鞭毛的丧失

• 批准号: 2243230
• 负责人: Jason Gallant
• 金额: $ 92.63万
• 依托单位: Michigan State University
• 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: 2023-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2243230&HistoricalAwards=false
• 关键词: Tale; No; Tail; Sperm; Flagella

This project investigates genetic and evolutionary factors behind the loss of conserved traits in weakly electric fishes, specifically mormyrids. Mormyrids are a group of over 200 species known for unique traits, including the ability to generate electric signals and the complete absence of flagella in their sperm. The research team recently discovered a partial deletion mutation in a gene that is essential for sperm flagella formation in mormyrids. The project uses gene editing in zebrafish to test whether this single mutation results in the loss of flagella in fishes, and investigates a newly discovered unique morphological trait of mormyrid eggs that may facilitate fertilization when flagella are absent. In addition, several hypotheses about the evolutionary causes of flagella loss in mormyrid sperm will be tested, providing a link between genetic mutations and the evolutionary forces that operate on them. By revealing effects of the mutation on other functional systems dependent upon cilia and flagella, the research may also provide novel insight into human ciliary disease. The project promotes teaching and training by integrating research outcomes into an undergraduate course and through training of a post-doctoral fellow, two graduate students, and several undergraduate student researchers.The objective of the project is to understand the genetic basis of the loss of flagella in sperm in weakly electric mormyrid fishes, a group of over 200 species known for their numerous derived and novel traits, including the evolution of electrogenesis, electroreception, and extreme encephalization. Interestingly, mormyrids are also the only known vertebrate group to completely lack flagella on their sperm. The research focuses on a highly conserved cilia- and flagella-related protein which plays a crucial role in the formation of sperm flagella and ciliary motility; the gene coding for this protein was recently discovered to have a partial deletion within mormyrids. By using CRISPR/Cas9 gene editing to create mutant zebrafish, the investigators will determine whether this deletion leads to flagellar loss, and what pleiotropic consequences of this mutation result for other ciliated cell types. Additionally, the project will examine sperm-egg interaction in mormyrids, test for evidence of sperm competition, and assess the hypothesis that sperm flagellar loss is driven by selection for energetically efficient testes. The study of mormyrids will provide important insights into the evolution of a unique vertebrate mating system and may also have implications for novel therapeutic interventions for primary ciliary dyskinesia in humans. In addition to educational and training impacts, the project also supports continuation of the EFISH Genomics Portal, a resource for the scientific community studying electric fishes.This project was co-funded by the BIO-IOS Physiological Mechanisms and Biomechanics Program and the Animal Developmental Mechanisms Program.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.

该项目调查了弱电鱼类（特别是长颌鱼）保守性状丢失背后的遗传和进化因素。Mormyrids是一个由200多个物种组成的群体，以其独特的特征而闻名，包括产生电信号的能力和精子中完全没有鞭毛。该研究小组最近发现了一个基因的部分缺失突变，该基因是mormyrids精子鞭毛形成所必需的。该项目使用斑马鱼的基因编辑来测试这种单一突变是否会导致鱼类鞭毛的丧失，并研究了一种新发现的独特形态学特征，即当鞭毛缺失时，这种形态学特征可能有助于受精。此外，几个假说的鞭毛损失的进化原因在mormyrid精子将进行测试，提供了一个基因突变和进化的力量，对他们的操作之间的联系。通过揭示突变对依赖于纤毛和鞭毛的其他功能系统的影响，该研究也可能为人类纤毛疾病提供新的见解。该项目通过将研究成果纳入本科课程并通过培训一名博士后研究员、两名研究生和几名本科生研究人员来促进教学和培训。该项目的目的是了解弱电象鼻鱼精子中鞭毛缺失的遗传基础，这是一个拥有200多个物种的群体，以其众多的衍生和新特征而闻名，包括电发生、电感受和极端脑化的进化。有趣的是，食蚁兽也是唯一已知的精子上完全没有鞭毛的脊椎动物。该研究的重点是一种高度保守的纤毛和鞭毛相关蛋白，该蛋白在精子鞭毛和纤毛运动的形成中起着至关重要的作用;最近发现编码这种蛋白的基因在mormyrids中有部分缺失。通过使用CRISPR/Cas9基因编辑来创建突变斑马鱼，研究人员将确定这种缺失是否会导致鞭毛丢失，以及这种突变对其他纤毛细胞类型的多效性后果。此外，该项目还将研究食蚁兽中的精卵相互作用，测试精子竞争的证据，并评估精子鞭毛损失是由能量有效的睾丸选择驱动的假设。对mormyrids的研究将为独特的脊椎动物交配系统的进化提供重要的见解，也可能对人类原发性纤毛运动障碍的新型治疗干预产生影响。除了教育和培训影响，该项目还支持继续EFISH基因组学门户网站，为研究电鱼的科学界提供资源。该项目由BIO共同资助，IOS生理机制和生物力学计划以及动物发育机制计划。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。