Genome-wide mapping of recombination hotspots in Arabidopsis

拟南芥重组热点的全基因组图谱

• 批准号: BB/K007882/1
• 负责人: Ian Henderson
• 金额: $ 43.27万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FK007882%2F1
• 关键词: Genome; wide; mapping; recombination; hotspots

Harnessing natural genetic variation through breeding and genetic recombination is a cornerstone of crop improvement. During domestication crops pass through genetic bottlenecks, meaning that wild progenitor species contain abundant variation that is useful to reintroduce. One limitation to breeding is that recombination rate is highly variable along chromosomes. For example, large regions of wheat, barley and maize chromosomes are non-recombining, despite containing useful genetic variation. We are investigating the mechanistic basis of recombination control, with the aim of rationally manipulating this process to accelerate crop breeding. As the core recombination process is highly conserved between plants, our work focuses on the model species Arabidopsis thaliana, which has extensive genetic and genomic resources. Using a novel experimental technique termed pollen-typing we have recently discovered that A.thaliana chromosomes have narrow hotspot regions with a highly elevated chance of recombination. These hotspots are located in gene promoters, where open chromatin packaging allows access to the DNA, and we hypothesize that this also allows access to the recombination machinery. Hotspots in other species are controlled by a combination of chromatin structure and primary DNA sequence, and we will investigate these relationships in A.thaliana. First we will use population genetics methods to generate a genome-wide hotspot map using patterns of natural genetic polymorphism between A.thaliana populations. As recombination breaks up blocks of linked genetic variation, this effect can be used to measure recombination rate and identify hotspot locations. The A.thaliana genome is well annotated with chromatin maps and this will allow us to determine which aspects of chromosome organisation correlate with hotspot locations. In addition we will test whether hotspots associate with specific DNA sequences, to resolve the extent to which plant hotspots are genetically versus epigenetically determined. Using pollen-typing we will then experimentally validate a subset of the most active hotspots in the A.thaliana genome. To directly test the role of chromatin on hotspot activity we will repeat pollen-typing in mutant backgrounds with altered epigenetic organization. The hotspots we have already observed are located in gene promoters and we will use mutants with altered promoter chromatin to test for effects on recombination. We will also directly target chromatin modifications associated with gene silencing to hotspots and investigate whether this is sufficient to suppress recombination. Knowledge of hotspot control will provide novel insight into manipulating recombination in crop genomes. Our strategic goal is to modulate hotspot activity in crops, for example by boosting, suppressing or relocating them, and thereby facilitating breeding of high-yielding strains.

通过育种和遗传重组来利用自然遗传变异是作物改良的基石。在驯化过程中，作物会通过遗传瓶颈，这意味着野生祖先物种含有丰富的变异，这些变异对重新引入有用。育种的一个限制是重组率沿染色体沿着高度可变。例如，小麦、大麦和玉米染色体的大部分区域是非重组的，尽管含有有用的遗传变异。我们正在研究重组控制的机制基础，目的是合理地操纵这一过程，以加速作物育种。由于核心重组过程在植物之间高度保守，我们的工作集中在具有广泛遗传和基因组资源的模式物种拟南芥上。利用一种新的实验技术，称为花粉分型，我们最近发现，拟南芥染色体具有狭窄的热点区域，重组的机会非常高。这些热点位于基因启动子中，开放的染色质包装允许进入DNA，我们假设这也允许进入重组机制。在其他物种的热点控制的染色质结构和初级DNA序列的组合，我们将调查这些关系在拟南芥。首先，我们将使用群体遗传学的方法来生成一个全基因组的热点图，利用模式的自然遗传多态性之间的拟南芥种群。由于重组打破了连锁遗传变异的块，这种效应可以用来测量重组率和确定热点位置。拟南芥基因组被染色质图谱很好地注释，这将使我们能够确定染色体组织的哪些方面与热点位置相关。此外，我们还将测试热点是否与特定的DNA序列相关，以解决植物热点在多大程度上是遗传与表观遗传决定的。使用花粉分型，我们将通过实验验证拟南芥基因组中最活跃的热点的子集。为了直接测试染色质对热点活性的作用，我们将在表观遗传结构改变的突变背景中重复花粉分型。我们已经观察到的热点位于基因启动子中，我们将使用具有改变的启动子染色质的突变体来测试对重组的影响。我们还将直接将与基因沉默相关的染色质修饰靶向热点，并研究这是否足以抑制重组。热点控制的知识将为操纵作物基因组中的重组提供新的见解。我们的战略目标是调节作物中的热点活动，例如通过提高、抑制或重新定位它们，从而促进高产菌株的育种。

项目成果

Nucleosomes and DNA methylation shape meiotic DSB frequency in Arabidopsis thaliana transposons and gene regulatory regions.

核小体和 DNA 甲基化塑造拟南芥转座子和基因调控区减数分裂 DSB 频率。

• DOI: 10.17863/cam.23795
• 发表时间: 2018
• 作者: Choi K

Massive crossover elevation via combination of HEI10 and recq4a recq4b during Arabidopsis meiosis.

在拟南芥减数分裂过程中，HEI10 和 recq4a、recq4b 的组合导致大量交叉升高。

• DOI: 10.17863/cam.25792
• 发表时间: 2018
• 作者: Henderson I

Contrasted patterns of crossover and non-crossover at Arabidopsis thaliana meiotic recombination hotspots.

• DOI: 10.1371/journal.pgen.1003922
• 发表时间: 2013-11
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Drouaud J;Khademian H;Giraut L;Zanni V;Bellalou S;Henderson IR;Falque M;Mézard C
• 通讯作者: Mézard C

Arabidopsis meiotic crossover hot spots overlap with H2A.Z nucleosomes at gene promoters.

• DOI: 10.1038/ng.2766
• 发表时间: 2013-11
• 期刊: NATURE GENETICS
• 影响因子: 30.8
• 作者: Choi, Kyuha;Zhao, Xiaohui;Kelly, Krystyna A.;Venn, Oliver;Higgins, James D.;Yelina, Nataliya E.;Hardcastle, Thomas J.;Ziolkowski, Piotr A.;Copenhaver, Gregory P.;Franklin, F. Chris H.;McVean, Gil;Henderson, Ian R.
• 通讯作者: Henderson, Ian R.

Recombination Rate Heterogeneity within Arabidopsis Disease Resistance Genes.

拟南芥抗病基因重组率异质性

• DOI: 10.1371/journal.pgen.1006179
• 发表时间: 2016-07
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Choi K;Reinhard C;Serra H;Ziolkowski PA;Underwood CJ;Zhao X;Hardcastle TJ;Yelina NE;Griffin C;Jackson M;Mézard C;McVean G;Copenhaver GP;Henderson IR
• 通讯作者: Henderson IR