RUI: Role of the haploidizer gene in genome elimination by a selfish B chromosome

这个项目旨在阐明自私的遗传因素如何扰乱正常的遗传模式。一类自私的元素--B染色体--在动植物中普遍存在。在某些情况下，B染色体会对生殖造成有害影响，并导致极端的性别比扭曲。在宝石黄蜂Nasonia vitriennis中，一条这样的B染色体会破坏来自父亲的部分基因组，导致全部雄性后代只携带来自母亲和B染色体的遗传物质。最近的研究发现了一种由B染色体表达的类似毒素的基因；该基因是B染色体基因组消除活动所必需的，使其成为已知的唯一在任何生物体中支撑自私染色体行为的基因。这项研究旨在揭示该基因如何在分子水平上发挥作用，为其他自私的遗传因素如何改变遗传模式提供洞察力。该项目将为不同群体的本科生和博士后研究员提供严格的研究培训机会。将围绕提案的目标之一开发一门新的基于实验室的课程；在这门课程中，学生将进行研究，通过动手实验学习科学实践。来自两年制大学水平的学生将参与这项研究，有助于提高他们在STEM的保留率，并增加他们继续进入四年制学位授予机构的可能性。总的来说，这项工作将有助于培养正在崛起的STEM劳动力。遗传学的一个隐含的假设是，基因组的元素为了有机体的适应而协同工作。然而，某些遗传因素不会以这种方式表现出来。这些被认为自私的基因违背了正常的遗传学规则，以获得遗传优势。自私的遗传因素带来的好处和有机体造成的伤害之间的这种对立，代表了一种鲜为人知的情况，称为基因组内冲突。这个项目将利用现代基因组学、遗传学、分子和细胞学的方法来研究一种名为单倍体的B染色体表达基因是如何导致宝石黄蜂Nasonia vitriennis的基因组消除的。主要活动包括：(1)使用转基因和其他基因操作方法来测试单倍化基因是单独发挥作用，还是与其他B染色体表达基因一起发挥作用；(2)使用高分辨率荧光显微镜在亚细胞水平上了解单倍化基因编码蛋白的特性；(3)利用遗传学方法确定单倍化蛋白的蛋白质相互作用；以及(4)使用基因组学方法来确定不同物种的类似B染色体是否也表达单倍化病毒样毒素基因，以导致基因组消除。这项研究将对B染色体如何通过单个基因的表达改变遗传遗传提供详细的调查。总的来说，这项研究将有助于阐明B染色体的行为如何与基因组中的标准染色体如此不同，并可能有助于努力建立更有效的人工基因表达系统，旨在控制携带疾病的害虫。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。

This project aims to elucidate how selfish genetic elements disrupt normal genetic inheritance patterns. A certain class of selfish elements – B chromosomes – are pervasive among plants and animals. In certain cases, B chromosomes cause harmful effects to reproduction and extreme sex ratio distortion. In the jewel wasp, Nasonia vitripennis, one such B chromosome destroys the part of the genome that comes from the father, resulting in all-male broods of progeny carrying hereditary material only from the mother and the B chromosome. Recent work has revealed a toxin-like gene expressed by this B chromosome; this gene is needed for the B chromosome’s genome elimination activity, making it the only gene known to underlie selfish chromosome behavior in any organism. This research aims to uncover how this gene functions at the molecular level, providing insights into how other selfish genetic elements alter inheritance patterns. The project will facilitate rigorous research training opportunities for a diverse group of undergraduate students and a postdoctoral researcher. A new laboratory-based course will be developed around one of the proposal’s aims; in this course, students will perform the research, learning the practice of science through hands-on experimentation. Students from the two-year college level will be involved in the research, helping to enhance their retention in STEM and the likelihood of their continuation to 4-year degree-granting institutions. Collectively, this work will help to train the rising STEM workforce.An implicit assumption of genetics is that elements of the genome function cooperatively for organismal fitness. However, certain genetic elements do not behave in this manner. Such elements, deemed selfish, disobey the normal rules of genetics to gain a transmission advantage. This opposition between the benefits gained by a selfish genetic element and the harm incurred by the organism represents a poorly understood condition known as intragenomic conflict. This project will utilize a combination of modern genomic, genetic, molecular, and cytological methods to study how a B chromosome-expressed gene called haploidizer causes genome elimination in the jewel wasp Nasonia vitripennis. The main activities include: (1) using transgenesis and other gene manipulation approaches to test if the haploidizer gene functions alone or instead with other B-chromosome expressed genes; (2) using high-resolution fluorescence microscopy to understand the properties of haploidizer’s encoded protein at the sub-cellular level; (3) using genetics to identify protein interactors of the haploidizer protein; and (4) using genomics approaches to determine if a similar B chromosome in a different wasp species also expresses a haploidizer-like toxin gene to cause genome elimination. This study will provide a detailed investigation of how B chromosomes alter genetic inheritance through the expression of individual genes. Broadly, the study will help to elucidate how B chromosomes behave so differently from the standard chromosomes in the genome, and it may facilitate efforts to build more effective artificial gene expression systems aimed at controlling disease-carrying insect pests.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.