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The juxtaposition of variability and stability in the HYP effectors of globally important plant-parasites.

全球重要植物寄生虫的 HYP 效应器的变异性和稳定性并存。

基本信息

批准号：
BB/S006397/1
负责人：
Sebastian Eves-Van Den Akker
金额：
$ 70.18万
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：
2019
资助国家：
英国
起止时间：
2019 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FS006397%2F1
关键词：
juxtaposition variability stability HYP effectors

项目摘要

Plant-parasitic nematodes threaten current and future global food security, and are estimated to cost world agriculture over $100 billion per year. In the UK, the most economically important species are the "potato cyst nematodes", which cause over £50 million of damages to the potato industry each year. Given that potato cyst nematodes are already present in every major potato growing region of the world, including emerging markets, a strong case can be made for exploring any area of parasite biology that may lead to new control measures. One area of parasite biology of increasing interest is "effectors" - nematode-derived molecules injected into the plant to cause disease.In this proposal we will focus our efforts on an unusual group of effectors called "HYPs", for two main reasons: Firstly, the genetics underlying HYPs are academically fascinating; Secondly, disrupting HYPs could lead to robust nematode control.Understanding the unusual genetics of HYP effectors: All of the 75 unique HYP genes identified to date share two continuous strings of coding sequence that are near identical between genes: together, these "conserved regions" make up approximately half of the total gene length. What is remarkable about HYPs is that between these two near-identical conserved regions lies a "hyper-variable domain". This hyper-variable domain can encode several "motifs" of variable sequence and organisation with almost no observable patterns. To add to the complexity, no one individual nematode genome encodes all HYPs, and no two individuals tested encode the same repertoire of HYPs. To the best of our knowledge, there is no known mechanism that can account for both the hyper-variable domain organisations and the gene number variation between sisters of the same population.To understand the combination of HYP genetic variability and stability, we need to know where HYPs are in the genomes of individuals, and how they are arranged. To do this we will use recent advances in technology to sequence HYP-containing ultra-long DNA molecules from individual nematodes. While we will not be able to determine whether any two molecules came from the same individual (even if they are identical), we can be absolutely certain that each read came from an individual. We can use these ultra-long DNA sequences, in combination with a high-quality consensus genome of the population, to explore the genetic basis of HYP genetic variability and stability.Disrupting HYP function: We know that the sequence of HYP genes are "evolutionarily constrained". The species which contain HYP effectors diverged from one another approximately 30 million years ago, and yet, since that time, the conserved regions of their HYP genes have remained almost unchanged. It stands to reason that there must be some explanation why the nucleotide sequence is so highly conserved, in spite of the tremendous diversity of the variable domain. Given the evolutionary constraint on HYPs, targeting the conserved regions in all HYP genes, in all potato cyst nematode species, may produce strong, durable, and broad spectrum resistance.To disrupt HYP function we propose to use a targeted approach called RNA interference. RNA interference can disrupt the function of a gene based on its sequence. By targeting RNA interference to the near-identical conserved regions, we can disrupt the function of all HYP genes, in all potato cyst nematodes. To deliver RNA interference to nematodes during infection, we will create transgenic potato plants that encode an RNA interference gene which targets the nematode HYPs. When the nematode feeds on the plant, they eat the interfering RNA, and their corresponding HYP genes are disrupted.This proposal thus combines interesting how/what/why pure science questions (about the genomic evolution of this system) with real potential for an agricultural impact.

植物寄生线虫威胁着当前和未来的全球粮食安全，据估计每年给世界农业造成超过1000亿美元的损失。在英国，经济上最重要的物种是“马铃薯胞囊线虫”，每年对马铃薯产业造成超过5000万英镑的损失。鉴于马铃薯胞囊线虫已经存在于世界上每个主要的马铃薯种植地区，包括新兴市场，因此可以充分利用探索可能导致新的控制措施的任何寄生虫生物学领域。寄生虫生物学的一个领域是越来越感兴趣的“效应物”--线虫衍生的分子注入植物中引起疾病。在本提案中，我们将把我们的努力集中在一组称为“HYPs”的不寻常的效应物上，主要有两个原因：首先，HYPs背后的遗传学在学术上很吸引人;其次，破坏HYPs可能导致强大的线虫控制。了解HYP效应物的不寻常遗传学：迄今为止，所有75个独特的HYP基因都有两个连续的编码序列，这些序列在基因之间几乎相同：这些“保守区域”共同构成了基因总长度的大约一半。关于HYPs的值得注意的是，在这两个几乎相同的保守区域之间存在一个“超变结构域”。这种超变结构域可以编码几个可变序列和组织的“基序”，几乎没有可观察到的模式。为了增加复杂性，没有一个单独的线虫基因组编码所有HYP，并且没有两个测试的个体编码相同的HYP库。据我们所知，没有已知的机制可以解释同一种群姐妹篇之间的高变结构域组织和基因数量变异。为了了解HYP遗传变异性和稳定性的组合，我们需要知道HYP在个体基因组中的位置，以及它们是如何排列的。为了做到这一点，我们将利用最新的技术进展，从单个线虫中测序含有HYP的超长DNA分子。虽然我们无法确定任何两个分子是否来自同一个个体（即使它们是相同的），但我们可以绝对肯定每个读数来自一个个体。我们可以利用这些超长的DNA序列，结合高质量的群体共有基因组，探索HYP遗传变异性和稳定性的遗传基础。破坏HYP功能：我们知道HYP基因的序列是“进化上受限制的”。含有HYP效应子的物种在大约3000万年前彼此分化，然而，从那时起，它们HYP基因的保守区域几乎保持不变。尽管可变结构域具有巨大的多样性，但核苷酸序列如此高度保守，这是理所当然的。鉴于HYPs的进化限制，靶向所有HYP基因的保守区域，在所有马铃薯孢囊线虫物种，可能会产生强大的，持久的，广谱的resistance.To破坏HYP功能，我们建议使用一种靶向的方法称为RNA干扰。RNA干扰可以根据基因的序列破坏基因的功能。通过将RNA干扰靶向到几乎相同的保守区域，我们可以破坏所有马铃薯胞囊线虫中所有HYP基因的功能。为了在感染过程中向线虫提供RNA干扰，我们将创建编码靶向线虫HYPs的RNA干扰基因的转基因马铃薯植物。当线虫以植物为食时，它们会吃掉干扰RNA，它们相应的HYP基因就会被破坏。因此，这个提议将有趣的如何/什么/为什么纯科学问题（关于这个系统的基因组进化）与农业影响的真实的潜力结合起来。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Genome Expression Dynamics Reveal the Parasitism Regulatory Landscape of the Root-Knot Nematode Meloidogyne incognita and a Promoter Motif Associated with Effector Genes.

DOI：
10.3390/genes12050771
发表时间：
2021-05-18
期刊：
Genes
影响因子：
3.5
作者：
Da Rocha M;Bournaud C;Dazenière J;Thorpe P;Bailly-Bechet M;Pellegrin C;Péré A;Grynberg P;Perfus-Barbeoch L;Eves-van den Akker S;Danchin EGJ
通讯作者：
Danchin EGJ

Nematode integrated management

线虫综合治理