Causes and consequences of microbe-mediated asexuality

微生物介导的无性繁殖的原因和后果

基本信息

批准号：
10714424
负责人：
Amelia Ryan Isis Lindsey
金额：
$ 35.62万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10714424
关键词：
Appearance Arthropods Asexual Reproduction Bacteria Bacterial Proteins Biological Models Biology Cell division Cellular biology Creativeness Defect Degenerative Disorder Development Drosophila genus Drug resistance Environment Eukaryota Evolution Fertility Gene Pool Genetic Genetic Variation Genomic approach Genomics Goals Health Human Inherited Insecta Interdisciplinary Study Link Malignant Neoplasms Maps Mediating Meiosis Microbe Mitosis Mitotic Modeling Molecular Organism Parthenogenesis Pathogenesis Pathogenicity Ploidies Process Proteins Quantitative Trait Loci Reproduction Reproductive Biology Research Rickettsia Sex Functioning Sexual Reproduction System Wolbachia Yeasts asexual asexuality comparative genomics forward genetics genome sequencing invention microbial novel novel therapeutics pathogen reproductive sex symbiont theories trait tumor

项目摘要

Project Summary Sexual reproduction evolved more than one billion years ago, shortly after the appearance of eukaryotes. Sex is theorized to be an important aspect of creating genetic variation, adapting to new environments, and in removing disadvantageous traits from the gene pool. Despite this, many eukaryotes have reverted to asexual reproductive strategies. Importantly, such transitions to asexual reproduction have huge evolutionary impacts: we see regular examples of this in the rapid spread of invasive, pathogenic, and drug-resistant organisms. Unfortunately, such transitions are notoriously difficult to mechanistically interrogate due to their lack of experimental tractability and the fact that many reversions to asexuality are quite ancient. However, arthropods are rich in recently acquired vertically inherited microbes (e.g., Wolbachia, Rickettsia, and Cardinium) that convert their arthropod hosts to asexual reproduction. So-called “parthenogenesis induction” has been reinvented multiple times across these bacteria and relies on microbial mechanisms for impacting host meiosis or mitosis to alter ploidy. We can manipulate these recently asexual lineages in the lab to mechanistically define the cell biology of asexual reproduction. Furthermore, because there are numerous independent transitions to microbe-mediated asexuality, and lineages will slowly undergo a loss of sexual function, we can use this system to track the genomic and mechanistic consequences of lost sex. The long-term goal of my lab is to link mechanistic processes of mitosis, meiosis, and reproduction to long-term organismal and genomic consequences. This proposal describes my lab’s research goals across the next five years, which include: (1) mechanistically characterizing bacterial proteins mediating asexual reproduction, (2) identifying mitotic- and meiotic- effector proteins across diverse bacteria and reproductive biologies, and (3) using forward genetics to map the genomic consequences of lost sex. Specifically, our creative interdisciplinary research plan integrates genomic approaches (e.g., genome sequencing, comparative genomics, quantitative trait loci mapping), molecular approaches in non-model organisms, and genetics in tractable model systems (e.g., yeast, Drosophila). We will build on our recent discovery of the first putative asexuality inducing bacterial effector proteins to broadly define how microbes have evolved to manipulate mitosis and meiosis, and disentangle the causes of reproductive switches from the consequences. In addition to the broad significance of reproduction, these systems afford new opportunities to understand fundamental aspects of cell biology that underly many human-health relevant processes. For example, defects in mitosis are typical of certain degenerative conditions and cancers, and changes in ploidy significantly contribute to fungal pathogenesis and drug resistance. Our focus on novel mechanisms for altering reproduction and cell division will support the development of new therapeutic avenues across a range of systems.

项目摘要在真核生物出现之后不久，有性繁殖发生了不久的十亿年前。理论上是创造遗传变异，适应新环境的重要方面从基因库中消除了不利的特征。尽管如此，许多真核生物已恢复到无性生殖策略。重要的是，这种向无性繁殖的转变具有巨大的进化影响：我们在侵入性，致病性和抗药性生物的迅速传播中进行了定期的例子。不幸的是，由于缺乏实验性障碍性以及许多逆转无性恋的事实非常古老。但是，节肢动物富含最近获得的垂直遗传的微生物（例如Wolbachia，Rickettsia和Cardinium）将其节肢动物宿主转换为无性繁殖。所谓的“孤py诱导”已经在这些细菌中多次重新发明，并依赖于影响宿主减数分裂的微生物机制或有丝分裂改变倍性。我们可以在实验室中操纵这些最近的无性谱系以机理定义无性繁殖的细胞生物学。此外，因为有许多独立向微生物介导的无性性的过渡，谱系将慢慢遭受性功能的丧失，我们可以使用该系统跟踪性别失去的基因组和机械后果。我实验室的长期目标是将有丝分裂，减数分裂和繁殖的机械过程与长期有机和基因组联系起来结果。该建议描述了我实验室在接下来的五年中的研究目标，包括：（1）机械地表征介导无性繁殖的细菌蛋白，（2）鉴定潜水细菌和生殖生物学的有丝分裂和减数分裂效应蛋白，（3）使用正向遗传学来绘制失去性别的基因组后果。具体来说，我们的创意跨学科研究计划综合基因组方法（例如，基因组测序，比较基因组学，定量性状基因座映射），非模型生物的分子方法以及遗传学可处理的模型系统（例如酵母，果蝇）。我们将建立在最近发现的第一个推定的基础上无性诱发细菌效应子蛋白的广泛定义微生物如何演变为操纵有丝分裂和减数分裂，并解散了繁殖切换的原因。此外为了繁殖的广泛意义，这些系统提供了新的机会来了解基本细胞生物学的各个方面在许多人类健康相关过程中。例如，有丝分裂缺陷是某些退化条件和癌症的典型特征，倍曲的变化显着有助于真菌发病机理和耐药性。我们关注改变繁殖和细胞的新型机制部门将支持各种系统中新的治疗途径的开发。