CAREER: Understanding the evolution and genetic basis of meiotic recombination rate

减数分裂重组是遗传多样性的重要来源，在生物适应中起着关键作用。减数分裂重组率在个体、种群和物种水平上差异很大。然而，对重组率变异的遗传基础和进化仍知之甚少。利用最先进的基因组技术，如单细胞测序和CRISPR-Cas9基因编辑，该项目将确定负责重组率变异的基因，并将阐明重组率是否由于自然选择而进化。此外，该项目将通过创新的、探究式的本科课程传播前沿的基因组知识，吸引不同背景的学生参与研究，并为K-12学生举办公共宣传活动。本项目将研究淡水微甲壳类水蚤（Daphnia pulex）和水蚤（d.p ulicaria）在分化过程中经历了强烈的分化选择的减数分裂重组率变化的进化和遗传基础。构建基因图谱的标准程序是费力的，而且很难扩大规模用于人口调查。本项目将开发一种基于组合索引的单精子基因组测序的新型高通量图谱系统。这将使数以百计的基因图谱的建设在一个经济和有效的方式。利用这种方法，本项目将对种内和种间的重组率变异进行全面的种群基因组分析。它还将研究适应性与中性重组率进化的基因组特征。这将有助于弥合经验数据与重组率进化理论之间的差距。最后，本项目将结合关联作图分析和CRISPR-Cas9基因编辑，鉴定水蚤重组率变异的致病基因和遗传变异，从而加深对减数分裂重组基因调控的认识。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。

Meiotic recombination is an important source of genetic diversity and plays a key role in organismal adaptation. Meiotic recombination rate varies greatly at the individual, population, and species level. However, the genetic basis and evolution of recombination rate variation remains poorly understood. Using state-of-the-art genomic techniques such as single-cell sequencing and CRISPR-Cas9 gene editing, this project will identify the genes responsible for recombination rate variation and will illuminate whether recombination rate evolves due to natural selection. Moreover, this project will disseminate cutting-edge genomic knowledge through an innovative, inquiry-based undergraduate curriculum, engaging students of diverse backgrounds in research, and hosting public outreach events for K-12 students. This project will examine the evolution and genetic basis of meiotic recombination rate variation in the freshwater microcrustacean species Daphnia pulex and D. pulicaria, which experienced strong divergent selection during their divergence. Standard procedures for constructing genetic maps are laborious and difficult to scale up for population surveys. This project will develop a novel high throughput system for mapping based on single-sperm genomic sequencing with combinatorial indexing. This will enable the construction of hundreds of genetic maps in an economical and efficient manner. Using this approach, this project will perform comprehensive population genomic analyses of recombination rate variation both within- and between-species. It will also examine the genomic signatures of adaptive vs. neutral evolution of recombination rate. This will help bridge the gap between empirical data and evolutionary theory on recombination rate evolution. Lastly, this project will identify causal genes and genetic variants for recombination rate variation in Daphnia by combining association mapping analyses and CRISPR-Cas9 gene editing, thereby enhancing understanding of genetic regulation of meiotic recombination.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.