CAREER: Evolution and Genetic Control of Variation in Meiotic Recombination

减数分裂产生的精子和卵细胞的DNA含量恰好是身体其他细胞的一半。在减数分裂期间，具有相似DNA序列的染色体在物理上结合并交换其DNA片段。这个过程被称为重组，它产生新的DNA组合，可以推动进化变化。重组还确保DNA被正确地分割成精子和卵细胞。重组缺陷会导致精子或卵子的DNA过少或过多。这种基因错误会导致不孕、流产，并导致人类发育障碍。染色体重组事件的频率和位置在男性和女性之间、个体之间和物种之间都有惊人的差异。这项研究计划旨在确定重组中自然变异的原因。所发现的重组变异机制可能对育性有普遍影响。因此，这项工作的发现可能会导致发现新的靶点，以改善具有农业和经济重要性的物种，并为确定不孕不育遗传机制的患者进行临床试验。该项目还将通过支持一系列协调的教育活动来造福社会，这些活动将在缅因州创造新的进化基因组学教育和研究机会。该项目将结合进化定量基因组方法和细胞遗传学方法，在种群和亚种水平上剖析雄性和雌性个体重组率变化的根本原因。计划中的研究将利用家鼠（小家鼠）中已建立的工具和资源来绘制在多个水平上导致重组变异的基因。提出的实验将测试关于形成重组变异的进化力量的新假设，并将探索重组与生育之间的关系。这些研究活动将为博士后培训提供一个平台，并将与大量的教学、指导和推广工作协同工作。具体而言，拟议的项目将(1)开发新的课程内容和材料，以提高缅因州高中基因组学教育的水平；(2)为本科生创造受指导的研究机会；(3)支持PI开发一门新的进化和种群基因组学研究生课程。总体而言，该职业发展计划将培养早期女性研究者，通过原创研究、指导和教育为科学做出重大的终身贡献。该奖项反映了美国国家科学基金会的法定使命，并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。

Meiosis gives rise to sperm and egg cells with precisely half the amount of DNA as other cells of the body. During meiosis, chromosomes with similar DNA sequence become physically joined and swap pieces of their DNA. This process is called recombination, and it produces new DNA combinations and can drive evolutionary change. Recombination also assures that the DNA is correctly partitioned into sperm and egg cells. Defects in recombination can result in sperm or eggs with too little or too much DNA. Such genetic errors can cause infertility, lead to miscarriage, and contribute to developmental disability in humans Both the frequency and the placement of recombination events along chromosomes are surprisingly variable between males and females, between individuals, and between species. This research program aims to identify the causes of natural variation in recombination. The discovered mechanisms of recombination variation may have general effects on fertility. Consequently, findings from this work could lead to the discovery of new targets for improving species of agricultural and economic importance as well as clinical tests for identifying patients with genetic mechanisms of infertility. This project will also benefit society by supporting a coordinated series of educational activities that will create new evolutionary genomics education and research opportunities in Maine. This project will combine evolutionary quantitative genomic methods and cytogenetic approaches to dissect the root causes of recombination rate variation in male and female individuals, and at the population and subspecies levels. The planned research will take advantage of established tools and resources in house mice (Mus musculus) to map genes that contribute to variation in recombination at multiple levels. The proposed experiments will test new hypotheses about the evolutionary forces that shape variation in recombination and will explore the relationship between recombination and fertility. These research activities will provide a platform for postdoctoral training and will synergize with substantial teaching, mentoring, and outreach efforts. Specifically, the proposed project will (1) develop new course content and materials to advance the state of genomics education in Maine high schools; (2) create mentored research opportunities for undergraduate students; and (3) support the PI’s development of a new graduate-level course in evolutionary and population genomics. Overall, this career development program will prepare an early-stage female investigator to make substantial life-long contributions to science through original research, mentoring, and education.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.