The mechanisms of segregation distortion in Drosophila

果蝇分离扭曲的机制

基本信息

  • 批准号:
    10576909
  • 负责人:
  • 金额:
    $ 30.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-03-15 至 2025-02-28
  • 项目状态:
    未结题

项目摘要

Project Summary Segregation distorters are selfish genetic elements that operate by over-representing themselves in the mature gamete pool, thus fundamentally violating Mendel’s law. The evolutionary arms races triggered between distorter genes and their suppressors have long been recognized as a powerful force that shapes the evolution of genomes, cells, and species. Despite the ubiquity and importance of segregation distorters, we understand very little about the genetic basis and molecular mechanisms of this class of selfish genetic elements. A key barrier in understanding the mechanisms of segregation distorters is that they are present in non-model systems that lack genetic tools, and are almost always associated with chromosomal inversions that thwart traditional genetic approaches to gene discovery. Without characterizing the underlying genetic basis and molecular mechanisms it remains impossible to directly connect the arms race initiated by selfish elements to broader phenomena in the evolution of meiosis and sex chromosome systems. Here, we develop two independent methods to side-step traditional barriers presented by chromosomal inversions to gene discovery, and dissect the genetic basis underlying this selfish behavior in closely related Drosophila species. In our first aim, we develop a mutagenesis approach to identify the genes causing Sex- Ratio distortion in D. pseudoobscura. Through a combination of sequencing, in silico complementation, bulked- segregant mapping, and CRISPR/ Cas9 based editing, we are poised to resolve the complex genetic architecture that underlies distortion and to identify the complete set of genes, including modifiers and enhancers, that drive the selfish behavior of the D. pseudoobscura Sex-Ratio chromosome. In our second aim, we uncover cryptic variation within species for suppressors of distortion. Here, we aim to understand the molecular arms races between distorters and their suppressors through the identification of the genes and mechanisms of suppression of segregation distortion, and suppressors of suppressors-of-distortion. In our third aim, we engineer a synthetic chromosomal inversion to allow recombination mapping of Sex-Ratio distortion in D. persimilis. This approach adapts the Flp/FRT site-specific recombination tools to generate a perfectly collinear non-driving chromosome to allow free recombination in the region containing all necessary and sufficient genes for SR distortion. Once candidate genes are mapped, validated, and organized into a functional pathway for D. persimilis, a comparative analysis of these two systems will test whether SR mechanisms are unique or shared. Together, this work will provide the most complete genetic architecture of sex-linked segregation distorters to date, open the door to understanding the molecular mechanisms of distortion in two Sex-Ratio systems, and for the first time explicitly test independent or shared origins and mechanisms of Sex-Ratio distortion in these closely related species.
项目摘要 分离扭曲者是自私的遗传因素,它们通过在成熟个体中过度表现自己来运作。 配子池,从而从根本上违反孟德尔定律。进化的军备竞赛引发了 扭曲基因及其抑制基因长期以来被认为是塑造进化的强大力量 基因组、细胞和物种。尽管种族隔离扭曲者无处不在,而且很重要,但我们知道, 关于这类自私遗传因子的遗传基础和分子机制的研究很少。一个关键 理解偏析畸变机制的障碍是它们存在于非模型中, 缺乏遗传工具的系统,几乎总是与染色体倒位有关, 传统的基因发现方法。如果不描述潜在的遗传基础, 分子机制,仍然不可能直接连接军备竞赛发起的自私因素, 减数分裂和性染色体系统进化中的更广泛现象。 在这里,我们开发了两种独立的方法,以绕过传统的染色体障碍, 基因发现的逆转,并剖析这种自私行为的遗传基础,在密切相关的 果蝇属。在我们的第一个目标中,我们开发了一种诱变方法来鉴定引起性- D中的比率失真。伪暗通过测序,计算机互补,放大- 分离作图和基于CRISPR/ Cas9的编辑,我们准备解决复杂的遗传问题。 结构的基础扭曲,并确定一套完整的基因,包括修改器和 增强子,驱动D.拟暗纹夜蛾性比染色体。在我们的第二个目标中, 我们揭示了物种内扭曲抑制因子的神秘变异。在这里,我们的目标是了解 通过识别基因,在扭曲者和抑制者之间进行分子军备竞赛, 抑制偏析畸变的机制和畸变抑制剂的抑制剂。在我们的第三 目的是,我们设计了一个合成的染色体倒位,以允许重组映射的性别比失真, D. Persimilis。该方法采用Flp/FRT位点特异性重组工具,以产生完美的 共线的非驱动染色体,以允许在含有所有必需的和 有足够的基因导致SR畸变一旦候选基因被定位、验证并组织成一个 功能途径D. persimilis,这两个系统的比较分析将测试是否SR 机制是唯一的或共享的。总之,这项工作将提供最完整的遗传结构, 迄今为止,性连锁隔离扭曲,打开了理解的分子机制的大门, 在两个性别比例系统的失真,并首次明确测试独立或共享的起源, 在这些密切相关的物种中性别比例扭曲的机制。

项目成果

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Nitin Phadnis其他文献

Nitin Phadnis的其他文献

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{{ truncateString('Nitin Phadnis', 18)}}的其他基金

The mechanisms of segregation distortion in Drosophila
果蝇分离扭曲的机制
  • 批准号:
    10369698
  • 财政年份:
    2021
  • 资助金额:
    $ 30.5万
  • 项目类别:
The mechanisms of segregation distortion in Drosophila
果蝇分离扭曲的机制
  • 批准号:
    10582443
  • 财政年份:
    2021
  • 资助金额:
    $ 30.5万
  • 项目类别:
The mechanisms of segregation distortion in Drosophila
果蝇分离扭曲的机制
  • 批准号:
    10186276
  • 财政年份:
    2021
  • 资助金额:
    $ 30.5万
  • 项目类别:
The molecular basis of speciation in Drosophila
果蝇物种形成的分子基础
  • 批准号:
    8945269
  • 财政年份:
    2015
  • 资助金额:
    $ 30.5万
  • 项目类别:

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