The Genetic Basis of Cytoplasmic Incompatibility

细胞质不相容的遗传基础

基本信息

  • 批准号:
    9366789
  • 负责人:
  • 金额:
    $ 38.16万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-05-24 至 2022-04-30
  • 项目状态:
    已结题

项目摘要

Project Summary Wolbachia offer a pesticide-free alternative to curb arbovirus transmission. Current pilot studies release infected mosquitoes to either crash the resident population size or spread mosquitoes with reduced vectorial capacity in the local population. Both efforts rely upon Wolbachia's adaptation to cause cytoplasmic incompatibility (CI) - a sperm modification that causes embryonic arrest in crosses between infected males and uninfected females (unidirectional CI) or between males and females harboring different Wolbachia strains (bidirectional CI). However, infected females with the same strain rescue the sperm modification, giving them a large fitness advantage over uninfected females that in turn enables rapid spread of Wolbachia through host populations. Despite four decades of intense research and current applications to vector control, the underlying genetic basis of CI has not been reported. However, we recently identified two prophage WO gene candidates in the released strain of wMel Wolbachia that natively infects Drosophila melanogaster. These genes are hereafter referred to as cytoplasmic incompatibility factor A (cifA) and cytoplasmic incompatibility factor B (cifB). cifA and cifB exhibit enhanced expression in infected host testes, as expected for genes involved in CI. Expression of cifA and cifB transgenes in uninfected D. melanogaster testes recapitulates induction of CI, while expression in Wolbachia- infected testes enhances the wild type CI. Importantly, wMel-infected females rescue the transgene-associated CI, thereby implicating these candidates as likely CI genes. Phylogenies specify divergent clades of cifA and cifB homologs that covary with bidirectional incompatibility relationships between Wolbachia strains. Additionally, recent genome sequencing and comparisons reveal candidate rescue genes that exhibit parallel phylogenies to those of cifA and cifB and preferential expression in early embryos. As these findings represent a potential breakthrough in the search for CI genes, the central hypothesis of the proposed research is that the candidate modification and rescue genes determine unidirectional and bidirectional CI. In Aim 1, we will use transgenic expression of genetically divergent cifA and cifB variants to broadly test the essential cif gene regions for inducing CI and whether extant homologs of these genes retain the ability to induce CI. In Aim 2, we will investigate candidate rescue genes from wMel using transgenic expression in females and crosses with an array of males with CI-inducing Wolbachia or transgene cif homologs. This aim will also explicitly test the presumption that divergence in modification and rescue genes underlies bidirectional CI. Examinations thus far have yet to yield a comprehensive genetic advance for both sides of CI, and the rising interest in deploying Wolbachia to curb arbovirus transmission necessitates an explanation of Wolbachia's drive system. If successful, this research will pioneer genetic studies of bacteria-induced reproductive parasitism, inform Wolbachia's efficacy and delivery as a tool to control diverse zoonotic diseases, and provide multiple lines of evidence for the discovery of genes that underlie CI.
项目概要 沃尔巴克氏菌提供了一种不含杀虫剂的替代品来遏制虫媒病毒的传播。目前的试点研究释放了感染者 蚊子要么会破坏常住人口规模,要么会在媒介能力降低的情况下传播蚊子 当地人口。这两项努力都依赖于沃尔巴克氏体的适应引起细胞质不相容性(CI)——a 精子修饰导致受感染的雄性和未受感染的雌性杂交时胚胎停滞 (单向 CI)或携带不同沃尔巴克氏体菌株的男性和女性之间(双向 CI)。 然而,具有相同菌株的受感染雌性挽救了精子的变异,使它们具有很大的适应性 与未感染的女性相比具有优势,这反过来又使沃尔巴克氏体能够在宿主群体中快速传播。 尽管对媒介控制进行了四十年的深入研究和当前应用,但潜在的遗传基础 CI 尚未见报道。然而,我们最近在发布的报告中发现了两个前噬菌体 WO 基因候选物 天然感染黑腹果蝇的 wMel Wolbachia 菌株。这些基因在下文中被称为 如细胞质不相容因子 A (cifA) 和细胞质不相容因子 B (cifB)。 cifA和cifB展览 与 CI 相关基因的预期一样,受感染宿主睾丸中的表达增强。 cifA和cifB的表达 未感染的黑腹果蝇睾丸中的转基因概括了 CI 的诱导,而在沃尔巴克氏体中的表达 受感染的睾丸增强了野生型 CI。重要的是,感染 wMel 的雌性拯救了与转基因相关的 CI,从而暗示这些候选基因可能是 CI 基因。系统发育指定 cifA 和 cifB 的不同分支 与沃尔巴克氏菌菌株之间双向不相容关系共变的同源物。此外, 最近的基因组测序和比较揭示了候选拯救基因,这些基因表现出与 cifA 和 cifB 的那些以及在早期胚胎中的优先表达。由于这些发现代表了潜在的 在寻找 CI 基因方面取得突破,本研究的中心假设是候选基因 修饰和拯救基因决定单向和双向CI。在目标 1 中,我们将使用转基因 表达遗传上不同的 cifA 和 cifB 变体,以广泛测试诱导的必需 cif 基因区域 CI 以及这些基因的现有同源物是否保留诱导 CI 的能力。在目标 2 中,我们将调查 使用雌性转基因表达并与一系列雄性杂交从 wMel 中拯救候选基因 与 CI 诱导的沃尔巴克氏体或转基因 cif 同源物。这一目标还将明确检验以下假设: 修饰和拯救基因的分歧是双向 CI 的基础。考试至今尚未有结果 CI 双方的全面基因进展,以及部署沃尔巴克氏体来遏制的兴趣日益浓厚 虫媒病毒的传播需要对沃尔巴克氏体的驱动系统进行解释。如果成功的话,这项研究将 对细菌引起的生殖寄生的开创性遗传学研究,揭示了沃尔巴克氏菌的功效和传递方式 控制多种人畜共患疾病的工具,并为发现基因提供多方面的证据 CI 的基础。

项目成果

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SETH R BORDENSTEIN其他文献

SETH R BORDENSTEIN的其他文献

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{{ truncateString('SETH R BORDENSTEIN', 18)}}的其他基金

The Mechanism of Cytoplasmic Incompatibility
细胞质不相容的机制
  • 批准号:
    10078245
  • 财政年份:
    2020
  • 资助金额:
    $ 38.16万
  • 项目类别:
The Mechanism of Cytoplasmic Incompatibility
细胞质不相容的机制
  • 批准号:
    9885060
  • 财政年份:
    2020
  • 资助金额:
    $ 38.16万
  • 项目类别:
The Mechanism of Cytoplasmic Incompatibility
细胞质不相容的机制
  • 批准号:
    10322407
  • 财政年份:
    2020
  • 资助金额:
    $ 38.16万
  • 项目类别:
The Mechanism of Cytoplasmic Incompatibility
细胞质不相容的机制
  • 批准号:
    10738499
  • 财政年份:
    2020
  • 资助金额:
    $ 38.16万
  • 项目类别:
The Genetic Basis of Cytoplasmic Incompatibility
细胞质不相容的遗传基础
  • 批准号:
    9901416
  • 财政年份:
    2017
  • 资助金额:
    $ 38.16万
  • 项目类别:
Molecular Evolution and Life Cycle of Wolbachia Bacteriophage
沃尔巴克氏菌噬菌体的分子进化和生命周期
  • 批准号:
    7848059
  • 财政年份:
    2008
  • 资助金额:
    $ 38.16万
  • 项目类别:
Molecular Evolution and Life Cycle of Wolbachia Bacteriohage
沃尔巴克氏菌噬菌体的分子进化和生命周期
  • 批准号:
    8098728
  • 财政年份:
    2008
  • 资助金额:
    $ 38.16万
  • 项目类别:
Molecular Evolution and Life Cycle of Wolbachia Bacteriohage
沃尔巴克氏菌噬菌体的分子进化和生命周期
  • 批准号:
    8288780
  • 财政年份:
    2008
  • 资助金额:
    $ 38.16万
  • 项目类别:
Molecular Evolution and Life Cycle of Wolbachia Bacteriohage
沃尔巴克氏菌噬菌体的分子进化和生命周期
  • 批准号:
    7506517
  • 财政年份:
    2008
  • 资助金额:
    $ 38.16万
  • 项目类别:
Molecular Evolution and Life Cycle of Wolbachia Bacteriohage
沃尔巴克氏菌噬菌体的分子进化和生命周期
  • 批准号:
    7676743
  • 财政年份:
    2008
  • 资助金额:
    $ 38.16万
  • 项目类别:

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