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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.

该项目旨在了解某些基因如何以比其他基因更高的频率传递给后代。遗传信息从父母到后代的流动通常是一个公平的过程，允许来自每个父母的基因有相同的可能性被传递。然而，在某些被称为减数分裂驱动的情况下，基因欺骗了系统，并有更高的可能性被传递。减数分裂驱动的一个经典例子是在玉米中发现的，其中一个被称为驱动蛋白的分子马达蛋白家族与特定的染色体区域结合，并将它们引导到卵细胞。该奖项下的工作集中在两个驱动蛋白马达蛋白称为Kindr和Trkin，这是相似的，但在不同的染色体区域引起减数分裂驱动。大多数实验的目的是确定这两种驱动蛋白如何结合到不同的区域。最终目标是设计新的驱动蛋白，使其与染色体上的新DNA序列结合，以测试它们是否会显示相同的特性并引起减数分裂驱动。该项目将把研究与教育结合起来，让主要是本科院校的学生参与实验，以测试啤酒酵母中玉米驱动蛋白的功能。这些研究成果将为染色体分离提供新的见解，从长远来看，可能使研究人员能够控制和改善有价值性状的传递。驱动蛋白的功能是在有丝分裂和减数分裂期间移动细胞内的货物并组织纺锤体，帮助确保正常的染色体分离。在玉米异常染色体10（Ab10）上编码的两种驱动蛋白，称为Kindr和Trkin，是显着的例外，它们作为自私基因进化，以支持它们自己的分离。为了做到这一点，它们获得了一种新的特性，即与称为旋钮的专门重复序列结合，并将其转化为能动的新着丝粒。遗传学证据表明，至少有一种驱动蛋白（Kindr）不直接结合，而是通过一种暂时称为Smd 13的中间因子结合。这项工作的目标是识别Smd 13并了解Kindr如何与它相互作用以结合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。最后一个目标是设计新版本的Kindr和Trkin，与玉米基因组中构建的合成重复序列结合，并测试合成成分是否促进减数分裂驱动。基于酵母的新着丝粒系统也将被开发，以测试驱动蛋白是否可以用于在异源宿主中移动染色体。该结果将扩大我们对植物驱动蛋白及其在减数分裂中作用的了解，并探索利用驱动蛋白介导的染色体运动来操纵染色体分离的实用性。该奖项由遗传学机制、细胞动力学和功能联合资助，以及生物科学理事会分子和细胞生物科学部的系统和合成生物学项目。该奖项反映了NSF的法定使命，通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。