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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。从父母到后代的遗传信息流动通常是一个公平的过程，允许来自父母双方的基因有同等的可能性被传递。然而，在一些被称为减数分裂驱动的情况下，基因欺骗了系统，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，在玉米中，一种被称为运动蛋白的分子马达蛋白家族结合到特定的染色体区域，并将它们定向到卵细胞。该奖项的工作重点是两种被称为Kindr和Trkin的动蛋白马达蛋白，它们相似，但在不同的染色体区域引起减数分裂驱动。大多数实验都是为了确定这两种动蛋白如何与不同的区域结合。最终目标是设计新的动蛋白，将其与染色体上的新DNA序列结合，以测试它们是否会显示出相同的特性并导致减数分裂驱动。该项目将把这项研究与教育结合起来，让以本科为主的机构的学生参与实验，测试啤酒酵母中玉米激动素的功能。综上所述，这些研究成果将对染色体分离产生新的见解，从长远来看，可能允许研究人员控制和改善有价值的片段的传递。Kinesins的功能是在细胞内移动货物，并在有丝分裂和减数分裂期间组织纺锤体，在那里它们有助于确保正常的染色体分离。玉米异常10号染色体(AB10)上编码的两个激动素，称为KindR和Trkin，是显著的例外，它们作为自私基因进化而有利于自己的分离。为了做到这一点，他们获得了一种新颖的特征，即结合到称为旋钮的特殊重复序列上，并将它们转化为可移动的新球。遗传证据表明，至少有一种Kinesin(Kindr)不是直接结合的，而是通过一种暂定为Smd13的中间因子结合的。这项工作的一个目标是识别Smd13，并了解Kindr如何与其相互作用以结合DNA。其他实验旨在了解Trkin是如何与DNA结合的，并解释它在减数分裂驱动中的作用。最终目标是设计新版本的Kindr和Trkin，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减数分裂驱动。一种基于酵母的新着丝粒系统也将被开发出来，以测试运动蛋白是否可以用于在异种宿主中移动染色体。这一结果将扩大我们对植物动蛋白及其在减数分裂中的作用的理解，并探索使用动蛋白介导的染色体运动来操纵染色体分离的效用。该奖项由生物科学局分子和细胞生物科学部的遗传学机制、细胞动力学和功能以及系统和合成生物学项目共同资助。该奖项反映了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。