CAREER: Targeted genome elimination by a selfish B chromosome in the jewel wasp Nasonia vitripennis

该项目旨在了解自私的遗传元素如何在分子水平上改变遗传模式。在珠宝黄蜂（Nasonia vitripennis）中，一种特殊的所谓B染色体可以诱导消除从父本遗传的所有基因，产生只包含母亲基因组基因的后代，以及B染色体本身。这是如何发生的尚不清楚，但这项研究应该提供重要的线索，可能阐明自私的DNA元素如何促进自己在这个和其他系统中的繁殖。该项目将为本科生和一名博士后提供培训机会。该项目产生的数据将用于一个新模块的原始研究，该模块将由PI纳入其发育生物学课程；新课程将为学生提供生物信息学和荧光显微镜方法的经验。该课程模块也将被纳入洛杉矶地区两年制大学的生物学课程。学生在这些课程中共同努力的一个科学成果将是为研究界建立一个新的基因表达资源。期望学生参与研究的教育成果包括：提高学生对科学探究的兴趣和概念理解；生物专业的留校率更高；两年制大学生在后续高级生物学课程中的学习成绩更高；提高了两年制大学到四年制大学的学生转学率。正常情况下，真核生物基因组的所有部分协同工作以确保正常的机体功能。然而，在某些情况下，单个染色体区域甚至整个染色体可以改变正常的生殖过程，以牺牲整个基因组为代价，以异常高的水平遗传给新的后代。目前，人们对这种被称为基因组内冲突的情况是如何在分子水平上发生的知之甚少。该项目将采用现代分子和细胞学方法来研究一个多余的（“额外的”）B染色体是如何完全破坏珠宝黄蜂的父系基因组的，从而实现近乎完美的B染色体传播。初步数据表明，基因组消除是通过一种机制来实现的，这种机制涉及与父系和母系基因组相关的染色质配置的差异。实验方法将验证这一假设如下：(1)定义当父系基因组被消除时，B染色体和父系基因组在染色质状态上的差异；(2)确定B染色体是否以及如何改变父系基因组的染色质状态；(3)探索新的B染色体表达的非编码rna作为父本基因组消除的潜在效应物的作用。这项研究将为染色质动力学的未知方面提供见解，解决自私B元件的基因组消除是否在机制上不同于其他生物体的基因组消除事件，并有助于辨别基因组内冲突如何从功能统一的基因组中产生。

This project seeks to understand how selfish genetic elements can alter patterns of genetic inheritance at the molecular level. In the jewel wasp, Nasonia vitripennis, a special so-called B chromosome can induce elimination of all the genes inherited from the paternal parent, producing progeny that contain genes just from the mother's genome, along with the B chromosome itself. How this happens is not clear, but this research should provide important clues that might shed light on how selfish DNA elements promote their own propagation in this and other systems. The project will provide training opportunities for undergraduate students and a postdoctoral researcher. Data generated by the project will be used for original research in a new module to be incorporated by the PI into his developmental biology course; the new course will provide the students with experience in both bioinformatics and fluorescence microscopy approaches. The course module will also be incorporated into the biology curricula of two-year colleges in the Los Angeles area. A scientific outcome of the collective efforts of students in these courses will be to establish a new gene expression resource for the research community. Educational outcomes of engaging students in research are expected to include: increased student interest and conceptual understanding of scientific inquiry; higher rates of retention as biology majors; higher academic performance of two-year college students in subsequent upper-level biology courses; and enhanced rates of transfer of students from two- to four-year institutions. Normally, all parts of the eukaryotic genome function in unison to insure normal organismal function. However, in some cases, individual chromosome regions and even whole chromosomes can alter normal reproductive processes in order to become transmitted at abnormally high levels to new progeny at the expense of the genome as a whole. Currently little is known about how this condition, known as intragenomic conflict, occurs at the molecular level. This project will employ modern molecular and cytological methods to investigate how a supernumerary ("extra") B chromosome completely destroys the paternal genome in the jewel wasp Nasonia vitripennis, thereby achieving near-perfect B chromosome transmission. Preliminary data suggest that genome elimination is targeted through a mechanism involving differences in the configuration of chromatin associated with the paternal vs. maternal genomes. Experimental approaches will test this hypothesis as follows: (1) define how the B chromosome and the paternal genome differ in their chromatin states when the paternal genome undergoes elimination; (2) determine whether and how the B chromosome initially alters the chromatin state of the paternal genome; and (3) explore the role of novel B chromosome-expressed non-coding RNAs as potential effectors of paternal genome elimination. This research will provide insights into unknown aspects of chromatin dynamics, address whether genome elimination by the selfish B element is mechanistically distinct from genome elimination events in other organisms, and help to discern how intragenomic conflict can arise from a functionally unified genome.