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，重组率变异的遗传基础和进化仍然知之甚少。利用最先进的基因组技术，如单细胞测序和CRISPR-Cas9基因编辑，该项目将确定导致重组率变异的基因，并将阐明重组率是否因自然选择而进化。此外，该项目将通过创新的、以探究为基础的本科课程传播尖端基因组知识，吸引不同背景的学生参与研究，并为K-12学生举办公共外联活动。本项目将研究在分化过程中经历强烈分化选择的淡水微型甲壳类物种普氏水蚤和牙根水蚤减数分裂重组率变异的进化和遗传基础。构建遗传图谱的标准程序费时费力，很难扩大到人口调查的规模。该项目将开发一种新的基于组合索引的单精子基因组测序的高通量作图系统。这将使以经济和高效的方式构建数百个遗传图谱成为可能。使用这种方法，该项目将对物种内和物种间的重组率变异进行全面的种群基因组分析。它还将检查适应性与中性重组率进化的基因组特征。这将有助于弥合重组率演化的经验数据和进化理论之间的差距。最后，这个项目将结合关联图谱分析和CRISPR-Cas9基因编辑，识别导致水蚤重组率变异的原因基因和遗传变异，从而增强对减数分裂重组的遗传调控的理解。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。

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.