CAREER: Functional and evolutionary analysis of de novo evolved genes in Drosophila male reproduction

职业：果蝇雄性繁殖中从头进化基因的功能和进化分析

• 批准号: 1652013
• 负责人: Geoffrey Findlay
• 金额: $ 78.09万
• 依托单位: College of the Holy Cross
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1652013&HistoricalAwards=false
• 关键词: CAREER; Functional; evolutionary; analysis; de

All species share many genes in common with other organisms, but each species has a handful of new genes that came into existence only recently and are thus either unique to that species or shared only with its closest relatives. In a variety of animal and plant species, many such newly evolved genes are thought to impact the male reproductive system. The goal of this project is to determine how newly evolved genes influence male reproductive success by focusing on those that affect sperm function in the fruit fly model system, Drosophila melanogaster. This research will generate important basic science knowledge about how new genes change reproductive systems to the benefit of their carriers. Its broader implications relate to the potential development of strategies that inhibit the reproduction of insect species that are agricultural pests or that transmit human diseases, such as the mosquitoes that carry malaria and the Zika virus. By establishing the importance of lineage-specific genes for male reproduction, this research may aid in the development of smart pesticides, or genetic manipulation strategies that target genes found only in the problematic insect species and not other beneficial insects in the surrounding environment. This project will also benefit society by increasing the participation of undergraduates in original research and supporting innovative mentoring programs that encourage the persistence of students from groups that are underrepresented in STEM disciplines. The research will be conducted at an exclusively undergraduate institution and will be carried out, in part, by students in an intermediate-level Genetics course and students conducting independent research in a faculty member's lab. The project will also support a program in which first-year college students from underrepresented groups join research labs immediately upon their arrival on campus, providing these students with a sense of community and introducing them to scientific research as they begin college. Finally, the project will support a student-run organization that pairs college students with girls from underserved public high schools for weekly mentoring sessions that include assistance with math and science skills.This project focuses specifically on so-called "de novo" genes that have recently evolved from non-coding DNA sequence. Previous research from a variety of taxa has focused on identifying these genes and studying their emergence within populations, but little is known about their specific molecular and cellular functions. Working in the safe and genetically tractable Drosophila melanogaster model system, this project will begin by using RNA interference to screen all de novo genes expressed in the testes for effects on male fertility. Genes whose expression is required for full fertility will become targets for functional characterization, which will be facilitated by the development of tagged transgenes, antibodies, and CRISPR/Cas9-mediated knockout mutant lines. These tools will be used in cytological experiments to investigate how each gene influences the process of spermatogenesis and/or the function of mature sperm after they are transferred to females. In parallel with these functional genetic analyses, the evolutionary history of each gene will be examined across related Drosophila species in order to understand how the gene arose from non-coding DNA sequence and how the protein it encodes has evolved since its emergence. For de novo genes that show signatures of rapid divergence between species, further genetic experiments will be conducted to determine the functional consequences of divergence. Taken together, these experiments will provide a comprehensive view of how the process of new gene creation can modify reproductive phenotypes.

所有物种都与其他生物体共享许多共同的基因，但每个物种都有少数新基因，这些基因是最近才出现的，因此要么是该物种独有的，要么是与其最近的亲戚共享的。在各种动物和植物物种中，许多新进化的基因被认为会影响雄性生殖系统。该项目的目标是确定新进化的基因如何影响男性生殖成功，重点是那些影响果蝇模型系统，果蝇精子功能。这项研究将产生关于新基因如何改变生殖系统以使其携带者受益的重要基础科学知识。其更广泛的影响涉及可能制定战略，抑制农业害虫或传播人类疾病的昆虫物种的繁殖，如携带疟疾和寨卡病毒的蚊子。通过确定谱系特异性基因对雄性生殖的重要性，这项研究可能有助于开发智能杀虫剂或基因操作策略，这些策略针对仅在有问题的昆虫物种中发现的基因，而不是周围环境中的其他有益昆虫。该项目还将通过增加本科生对原创研究的参与和支持创新的指导计划来造福社会，这些计划鼓励来自STEM学科代表性不足的群体的学生坚持下去。这项研究将在一个专门的本科院校进行，部分将由中级遗传学课程的学生和在教师实验室进行独立研究的学生进行。该项目还将支持一项计划，其中来自代表性不足群体的一年级大学生在抵达校园后立即加入研究实验室，为这些学生提供社区意识，并在他们开始大学时向他们介绍科学研究。最后，该项目将支持一个学生组织，该组织将大学生与来自服务水平低下的公立高中的女孩配对，每周进行一次辅导，包括数学和科学技能方面的帮助。该项目特别关注最近从非编码DNA序列进化而来的所谓“从头”基因。以前的研究集中在识别这些基因并研究它们在种群中的出现，但对它们的特定分子和细胞功能知之甚少。在安全和遗传上易处理的果蝇模型系统中工作，该项目将开始通过使用RNA干扰来筛选睾丸中表达的所有从头基因对雄性生育力的影响。完全生育力所需表达的基因将成为功能表征的目标，这将通过开发标记的转基因，抗体和CRISPR/Cas9介导的敲除突变株系来促进。这些工具将用于细胞学实验，以研究每个基因如何影响精子发生的过程和/或成熟精子转移到雌性后的功能。与这些功能性遗传分析同时进行的是，每个基因的进化历史将在相关的果蝇物种中进行研究，以了解该基因是如何从非编码DNA序列中产生的，以及它编码的蛋白质自出现以来是如何进化的。对于显示物种间快速分化特征的从头基因，将进行进一步的遗传实验以确定分化的功能后果。总之，这些实验将提供一个新的基因创造过程如何改变生殖表型的全面视图。

项目成果

The Goddard and Saturn Genes Are Essential for Drosophila Male Fertility and May Have Arisen De Novo

• DOI: 10.1093/molbev/msx057
• 发表时间: 2017-05-01
• 期刊: MOLECULAR BIOLOGY AND EVOLUTION
• 影响因子: 10.7
• 作者: Gubala, Anna M.;Schmitz, Jonathan F.;Findlay, Geoffrey D.
• 通讯作者: Findlay, Geoffrey D.

A Well-Researched Book in Search of an Audience: Making Sense of Genes by Kostas Kampourakis

• DOI: 10.1187/cbe.18-02-0028
• 发表时间: 2018
• 期刊: CBE Life Sciences Education
• 作者: Findlay GD

Molecular evolution of the sex peptide network in Drosophila

• DOI: 10.1111/jeb.13597
• 发表时间: 2020-02-10
• 期刊: JOURNAL OF EVOLUTIONARY BIOLOGY
• 影响因子: 2.1
• 作者: McGeary, Meaghan K.;Findlay, Geoffrey D.
• 通讯作者: Findlay, Geoffrey D.