BTT EAGER: Controlling meiotic recombination in crops by manipulating DNA methylation

减数分裂重组是一个过程，其中两个亲本染色体，一个来自父亲，一个来自母亲，在有性生殖过程中物理交换部分以产生下一代。进化是物种进化和遗传变异背后的主要力量，是几乎所有植物和动物育种的基础。这些关键事件并不是沿着染色体均匀分布的。特别是，在许多具有大基因组的植物物种中，包括大多数作物，重组往往发生在染色体末端附近。相比之下，染色体的中心部分很大程度上缺乏重组，这对作物育种造成了重大障碍。该项目的目标是更好地了解细胞中的DNA修饰如何影响作物的减数分裂重组。在理解重组方面的最新进展表明，染色体上重组事件的分布可以通过减少DNA甲基化来改变，DNA甲基化是一种特殊的天然DNA分子修饰类型。该项目将阐明DNA甲基化如何影响重组。它还将研究是否可以在繁殖过程中人为控制DNA甲基化以改变重组模式，这对植物育种非常有用。获得增加染色体低重组区域重组的能力将允许育种者创造位于这些区域的基因的新组合，并帮助他们生产上级作物品种。该项目是与英国伯明翰大学的Chris富兰克林博士和Eugenio Sanchez-Moran博士合作进行的，作为推进作物育种和功能基因组学（BTT）突破性技术倡议的一部分。因此，由单轮减数分裂重组产生的遗传变异是有限的。此外，在包括大多数作物的具有大基因组的植物中，杂交的分布高度偏向于染色体末端。广泛的间质和近着丝粒染色体区域很少重组。然而，这些大的基因组区域包含了玉米中大约五分之一的基因，在其他一些作物中甚至更大的基因片段，这对植物育种构成了严重的障碍。最近的研究表明，DNA甲基化是控制哪些双链断裂成为交叉位点的关键因素，从而形成交叉景观。然而，重组和DNA甲基化之间的确切关系尚不清楚。该项目旨在阐明DNA甲基化如何在机制水平上影响重组模式，并为通过改变DNA甲基化控制作物交叉景观的方法奠定基础。为了阐明DNA甲基化对减数分裂重组的影响，将开发使用DNA甲基化抑制剂瞬时改变减数分裂中DNA甲基化模式的方案。化学去甲基化的植物和选择的DNA甲基化缺陷突变体将用于确定减数分裂的哪些步骤和过程被DNA甲基化改变。该研究将在玉米和芜菁中进行，以探索单子叶植物和双子叶植物基因组的行为。该奖项反映了NSF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 a process in which two parental chromosomes, one from the father and one from the mother, physically exchange parts to give rise to the next generation during sexual reproduction. Recombination is a major force behind species evolution and genetic variation, and is the basis of nearly all plant and animal breeding. These crucial events are not evenly distributed along chromosomes. In particular, in many plant species with large genomes, including most crops, recombination tends to take place near chromosome ends. In contrast, central portions of chromosomes largely lack recombination, causing a major obstacle to crop breeding. The goal of this project is to better understand how modifying DNA in the cell affects meiotic recombination in crops. Recent advances in understanding recombination suggest that the distribution of recombination events on chromosomes can be altered by reducing DNA methylation, a special, naturally occurring type of modification of DNA molecules. This project will elucidate how exactly DNA methylation affects recombination. It will also examine whether DNA methylation can be artificially controlled during reproduction to change recombination patterns, which will be very useful for plant breeding. Gaining the ability to increase recombination in low-recombination regions of chromosomes will allow breeders to create novel combinations of genes that are located in these regions, and help them produce superior crop varieties. This project is conducted in collaboration with Drs. Chris Franklin and Eugenio Sanchez-Moran at the University of Birmingham, UK, as part of the Breakthrough Technologies to Advance Crop Breeding and Functional Genomics (BTT) initiative.Recombination is initiated by the formation of numerous programmed double-strand breaks in chromosomal DNA, a small proportion of which are processed to form crossovers. Thus, the genetic variation generated by a single round of meiotic recombination is limited. Furthermore, the distribution of crossovers in plants with large genomes, which include most crops, is highly biased towards chromosomes ends. Extensive interstitial and centromere-proximal chromosome regions rarely recombine. Yet, these large genome areas contain roughly one-fifth of the genes in maize and even larger gene fractions in some other crops, which presents a serious impediment to plant breeding. Recent studies indicate that DNA methylation is a critical factor controlling which double-strand breaks become the sites of crossovers, thus shaping crossover landscape. However, the exact relationship between recombination and DNA methylation is not understood. This project seeks to elucidate how DNA methylation affects recombination patterns at the mechanistic level and lay foundations for methods to control crossover landscapes in crops by altering DNA methylation. To elucidate the effect of DNA methylation on meiotic recombination, a protocol to transiently alter DNA methylation patterns in meiosis using DNA methylation inhibitors will be developed. Chemically demethylated plants and selected mutants defective in DNA methylation will be used to determine which steps and processes of meiosis are altered by DNA methylation. The study will be conducted in maize and Brassica rapa, to explore the behavior of both monocot and dicot genomes.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.