Rebuilding a kinesin-based meiotic drive system from defined components

从定义的组件重建基于驱动蛋白的减数分裂驱动系统

基本信息

批准号：
1925546
负责人：
R Kelly Dawe
金额：
$ 104.42万
依托单位：
University of Georgia Research Foundation Inc
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1925546&HistoricalAwards=false
关键词：
Rebuilding kinesin based meiotic drive

项目摘要

This project aims to understand how some genes can be transmitted to progeny at higher frequencies than others. The flow of genetic information from parents to offspring is usually a fair process that allows genes from each parent to have an equal likelihood of being passed on. However, in some cases known as meiotic drive, genes cheat the system and have a higher likelihood of being passed on. A classic example of meiotic drive is found in maize, where a family of molecular motor proteins known as kinesins bind to specific chromosome regions and direct them to the egg cells. Work under this award is focused on two kinesin motor proteins known as Kindr and Trkin, which are similar, but cause meiotic drive at different chromosomal regions. Most of the experiments are designed to determine how the two kinesins bind to different regions. The ultimate aim is to engineer new kinesins that will bind to novel DNA sequences on chromosomes to test if they will show the same properties and cause meiotic drive. The project will integrate the research with education by engaging students at a predominantly undergraduate institutions in experiments to test the function of the maize kinesins in brewer's yeast. Together, the research outcomes will yield new insights into chromosome segregation, and in the long term, may allow researchers to control and improve the transmission of valuable traits.Kinesins function to move cargo within cells and organize spindles during mitosis and meiosis, where they help to ensure normal chromosome segregation. Two kinesins encoded on maize Abnormal chromosome 10 (Ab10), called Kindr and Trkin, are remarkable exceptions that evolved as selfish genes to favor their own segregation. To do this they have acquired the novel feature of binding to specialized repeat arrays called knobs and converting them into motile neocentromeres. Genetic evidence suggests that at least one of the kinesins (Kindr) does not bind directly, but through an intermediate factor tentatively called Smd13. A goal of this work is to identify Smd13 and understand how Kindr interacts with it to bind DNA. Other experiments are designed to understand how Trkin binds to DNA and interpret its role in meiotic drive. A final aim is to engineer new versions of Kindr and Trkin that bind to synthetic repeat arrays built into the maize genome and test whether the synthetic components promote meiotic drive. A yeast-based neocentromere system will also be developed to test whether kinesins can be used to move chromosome in a heterologous host. The results will expand our understanding of plant kinesins and their roles in meiosis and explore the utility of using kinesin-mediated chromosome movement to manipulate chromosome segregation.This award was jointly funded by the Genetics Mechanisms, Cellular Dynamics and Function, and Systems and Synthetic Biology Programs in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences.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.

该项目旨在了解如何以比其他基因更高的频率传输到后代。遗传信息从父母到后代的流动通常是一个公平的过程，可以使每个父母的基因都具有同等的可能性。但是，在某些情况下称为减数分裂驱动器，基因欺骗了该系统，并具有更高的传递可能性。在玉米中发现了一个减数分裂驱动的经典例子，其中一个被称为驱动蛋白的分子运动蛋白家族与特定的染色体区域结合，并将其引导到卵细胞。该奖项的工作集中在两个动力蛋白运动蛋白上，称为Kindr和Trkin，它们相似，但在不同的染色体区域引起减数分裂驱动。大多数实验旨在确定两个驱动蛋白如何与不同区域结合。最终目的是设计将与染色体上新型DNA序列结合的新型驱动蛋白测试它们是否会显示出相同的特性并导致减数分裂驱动。该项目将通过让学生在本科机构中吸引学生进行实验，以测试啤酒酵母中玉米驱动素的功能，从而将研究与教育融为一体。总之，研究结果将产生对染色体隔离的新见解，从长远来看，研究人员可以控制和改善有价值的特征的传播和改善有价值的特征。在玉米异常的染色体10（AB10）上编码的两个驱动剂，称为Kindr和Trkin，是显着的例外，它们以自私的基因发展为偏爱自己的隔离。为此，他们获得了与称为旋钮的专用重复阵列结合并将其转换为运动新中心粒子的新颖特征。遗传证据表明，至少一种驱动蛋白（Kindr）不直接结合，而是通过暂定称为SMD13的中间因素结合。这项工作的一个目标是识别SMD13并了解Kindr如何与之相互作用以结合DNA。其他实验旨在了解Trkin如何与DNA结合并解释其在减数分裂驱动中的作用。最终的目的是设计Kindr和Trkin的新版本，这些版本与玉米基因组中内置的合成重复阵列结合并测试合成成分是否促进了减数分裂驱动。还将开发基于酵母的新中心粒系统，以测试是否可以使用驱动蛋白在异源宿主中移动染色体。结果将扩大我们对植物动力蛋白及其在减数分裂中的作用的理解，并探索使用动力蛋白介导的染色体运动来操纵染色体的染色体分离。该奖项由遗传学机制，细胞动力学和功能，系统和系统生物学在分子和蜂窝状生物学的生物学领域共同资助。法定任务，并被认为是值得通过基金会的智力优点和更广泛影响的审查标准来评估的值得支持的。