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

这个项目试图了解自私的遗传因素如何在分子水平上改变遗传模式。在宝石黄蜂Nasonia vitriennis中，一种特殊的所谓B染色体可以导致从父本继承的所有基因的消除，产生的后代只包含来自母亲基因组的基因，以及B染色体本身。目前还不清楚这是如何发生的，但这项研究应该会提供重要的线索，可能会揭示自私的DNA元素如何在这个系统和其他系统中促进自己的繁殖。该项目将为本科生和博士后研究员提供培训机会。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并入他的发育生物学课程；新课程将为学生提供生物信息学和荧光显微镜方法方面的经验。该课程模块还将被纳入洛杉矶地区两年制大学的生物学课程。这些课程的学生集体努力的一个科学成果将是为研究社区建立一个新的基因表达资源。让学生参与研究的教育成果预计将包括：提高学生对科学探究的兴趣和概念理解；更高的生物专业保留率；两年制大学生在随后的高级生物学课程中的更高学习成绩；以及提高学生从两年制院校到四年制院校的转化率。正常情况下，真核生物基因组的所有部分都一致地发挥作用，以确保正常的生物功能。然而，在某些情况下，个别染色体区域甚至整个染色体可以改变正常的生殖过程，以便以异常高的水平传递给新的后代，而损害整个基因组。目前，人们对这种称为基因组内冲突的情况在分子水平上是如何发生的知之甚少。这个项目将使用现代分子和细胞学方法来研究额外的B染色体如何完全破坏宝石黄蜂Nasonia vitriennis的父系基因组，从而实现近乎完美的B染色体传递。初步数据表明，基因组消除是通过一种机制来实现的，该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)确定当父亲的基因组经历消除时，B染色体和父亲基因组的染色质状态如何不同；(2)确定B染色体最初是否以及如何改变父亲基因组的染色质状态；以及(3)探索新的B染色体表达的非编码RNA作为父亲基因组消除的潜在效应者的作用。这项研究将提供对染色质动力学未知方面的见解，解决自私B元件的基因组消除是否在机械上有别于其他生物中的基因组消除事件，并有助于区分功能统一的基因组如何引起基因组内冲突。

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.