EpiSpiX - Unlocking plant genetic diversity via epi-modification & targeted recombination.

EpiSpiX - 通过表观修饰解锁植物遗传多样性

• 批准号: BB/N007557/1
• 负责人: Ian Henderson
• 金额: $ 68.88万
• 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: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN007557%2F1
• 关键词: EpiSpiX; Unlocking; plant; genetic; diversity

It is vital that we continue to improve and adapt our most important crops to meet the challenges of an increasing global population and the changing climate. A major component of crop improvement is via classical crop breeding. In this approach breeders combine varieties of crops with complementary beneficial characteristics and use the natural process of recombination to recover strains that combine both sets of desirable features from the original parents. Recombination occurs between the generations when plants form sex cells (gametes) and therefore by understanding the processes that occur at this stage we will be able to breed useful strains faster and more effectively. This is important as recombination patterns can severely limit our ability to breed crop species. For example, if we consider the extremely large wheat genome (~16x larger than the human genome), recombination shows a highly skewed distribution and occurs in a minority of the DNA sequence. Despite large parts of the wheat genome being essentially silent for recombination, these regions can contain many important genes and useful variation. Therefore, these patterns can inherently limit the ability of breeders to improve our crops. As one example, the dwarfing gene RhtD1, which contributed to yield increases achieved during the Green Revolution, is located in one such non-recombining region. This has limited the ability of breeders to combine RhtD1 with other useful genes located in proximity, including important disease resistance genes. This problem is known as linkage-drag.We are investigating the hypothesis that a major cause for suppressed recombination in these genomic regions is at the level of organisation that we term epigenetic. This concept describes organisation of the genome beyond the DNA base sequence itself. A well understood example of this is that the cytosine bases in the DNA can be modified with methyl groups and this modification can act as a type of grammar that influences how the DNA is expressed. We have previously shown that epigenetic information can have a major effect on patterns of recombination. In the proposed work we will alter epigenetic information in plant genomes and profile exactly how the recombination process changes. We will undertake this both in the model species Arabidopsis and also directly in the complex wheat genome. This will involve collaboration with the group of Pierre Sourdille (Clermont-Ferrand) who is an expert at mapping recombination in the hexaploid bread wheat genome. This proposal is also an industrial collaboration with Meiogenix who are pioneering advanced technology to direct the recombination machinery to specific locations in the genome. They key idea in this proposal is to combine these targeting technologies with manipulation of chromatin to effectively unlock recombination in silent regions of plant chromosomes. Through this work we will provide knowledge and technology that will allow variation to be accessed in breeding programmes that was previously unavailable, due to restricted distributions of recombination. These ambitious research aims capitalise on the unique knowledge and research experience of the partners and will bring novel approaches to solving the problem of recombination control.

至关重要的是，我们必须继续改进和适应我们最重要的作物，以应对全球人口增长和气候变化的挑战。作物改良的一个主要组成部分是通过传统的作物育种。在这种方法中，育种者将具有互补有益特征的作物品种组合起来，并利用自然的重组过程从原始亲本中恢复具有两组理想特征的品种。当植物形成性细胞（配子）时，重组发生在世代之间，因此通过了解这一阶段发生的过程，我们将能够更快、更有效地培育出有用的菌株。这一点很重要，因为重组模式会严重限制我们培育作物品种的能力。例如，如果我们考虑非常大的小麦基因组（比人类基因组大16倍），重组显示出高度倾斜的分布，并且发生在少数DNA序列中。尽管小麦基因组的大部分对重组基本上是沉默的，但这些区域可能包含许多重要的基因和有用的变异。因此，这些模式从本质上限制了育种者改良作物的能力。例如，在绿色革命期间促成产量增加的矮化基因RhtD1就位于这样一个非重组区域。这限制了育种者将RhtD1与邻近的其他有用基因（包括重要的抗病基因）结合起来的能力。这个问题被称为链接拖动。我们正在研究这样一个假设，即在这些基因组区域中抑制重组的主要原因是在我们称之为表观遗传的组织水平上。这个概念描述了DNA碱基序列本身之外的基因组组织。一个很好的例子是DNA中的胞嘧啶碱基可以用甲基修饰，这种修饰可以作为一种语法，影响DNA的表达方式。我们以前已经表明，表观遗传信息可以对重组模式产生重大影响。在拟议的工作中，我们将改变植物基因组中的表观遗传信息，并准确地描述重组过程如何变化。我们将在模式物种拟南芥和复杂的小麦基因组中直接进行这一研究。这将涉及与Pierre Sourdille （Clermont-Ferrand）小组的合作，他是六倍体面包小麦基因组重组图谱的专家。该提案也是与Meiogenix的工业合作，Meiogenix是领先的先进技术，将重组机器引导到基因组的特定位置。他们提出的关键思想是将这些靶向技术与染色质操纵结合起来，有效地解开植物染色体沉默区域的重组。通过这项工作，我们将提供知识和技术，使以前由于重组分布有限而无法在育种计划中获得的变异得以实现。这些雄心勃勃的研究目标是利用合作伙伴的独特知识和研究经验，并将为解决重组控制问题带来新的方法。

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

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

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

• DOI: 10.1101/160911
• 发表时间: 2017-07
• 期刊: bioRxiv
• 作者: Kyuha Choi;Xiaohui Zhao;Christophe Lambing;C. Underwood;Thomas J. Hardcastle;Heïdi Serra;Andrew J. Tock;Piotr A. Ziolkowski;Nataliya E. Yelina;R. Martienssen;I. Henderson