CAREER: The genetic mechanisms of sex-ratio meiotic drive and resistance

人们普遍认为寄生虫是寄主的主要负担，但许多人没有意识到寄生虫的大部分负担来自寄主自己的基因组。这项建议旨在了解一种这种基因组内寄生虫的遗传基础。基因组内寄生虫与一般生物学过程有关，如新物种的创造和基因组的染色体组成，以及不孕不育等人类健康问题。最近，研究人员致力于采用基因组寄生虫来控制蚊子等害虫种群。因此，了解这些寄生虫的遗传基础可能有助于a)我们对基本生物学过程的理解，b)与不孕不育有关的问题，以及c)基因组内寄生虫在生物防治措施中的应用。该项目的一部分将包括为最近转学的学生提供研究机会，试图提高这一历史上脆弱群体的留存和满意度。该项目专门研究性别比减数分裂驱动，这种现象是携带特定基因或X染色体突变的男性产生女性偏见的性别比例，因为父亲的X染色体以某种方式能够干扰携带Y的精子的发育。方法是使用基因表达、细胞学和基因组技术，然后进行基因组编辑，以开发和测试涉及性别比减数分裂驱动的基因的假设。该项目的第二部分将使用类似的技术剖析Y连锁抗性对性别比减数分裂驱动的遗传基础。该提案的第三个目标是了解这些基因组内寄生虫如何导致自然选择实际上有利于减数分裂过程中不正确的染色体分离，从而导致配子缺失性染色体。该奖项由分子和细胞生物科学部门的遗传机制小组和环境生物学部门的进化过程小组共同资助。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。

It is widely recognized that parasites are a major burden for their hosts, but many people don’t recognize that much of the parasite burden comes from within the host’s own genome. This proposal aims to understand the genetic basis of one such intragenomic parasite. Intragenomic parasites are associated with general biological processes such as the creation of new species and the chromosomal makeup of the genome as well as human health issues like infertility. Recently, researchers have worked to adopt genomic parasites to control pest populations such as mosquitoes. Thus, understanding the genetic basis of these parasites may inform a) our understanding of basic biological processes, b) issues related to infertility, and c) applications of intragenomic parasites for biocontrol measures. Part of the project will involve providing research opportunities to recent transfer students in an attempt to improve retention and satisfaction of this historically vulnerable population.This project specifically examines sex-ratio meiotic drive, a phenomenon where males carrying a specific gene or mutation on the X chromosome produce female-biased sex ratios because the paternal X chromosome is somehow able to interfere with the development of Y-bearing sperm. The approach is to use gene expression, cytology and genomic techniques followed by genome editing to develop and test hypotheses about the genes involved in sex-ratio meiotic drive. The second part of the project will dissect the genetic basis of Y-linked resistance to sex-ratio meiotic drive using similar techniques. The third goal of the proposal is to understand how these intragenomic parasites might cause natural selection to actually favor improper segregation of chromosomes during meiosis leading to gametes missing sex chromosomes. This award was co-funded by the Genetic Mechanisms Cluster in the Division of Molecular and Cellular Biosciences and the Evolutionary Processes Cluster in the Division of Environmental Biology.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.