Collaborative Research: Rapid and Pervasive Mitochondrial Heteroplasmy with Recombination in a Remerging Ectoparasite

合作研究：快速而普遍的线粒体异质性与重新出现的外寄生虫中的重组

• 批准号: 1754394
• 负责人: Warren Booth
• 金额: $ 44.83万
• 依托单位: University of Tulsa
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1754394&HistoricalAwards=false
• 关键词: Collaborative; Research; Rapid; Pervasive; Mitochondrial

Mitochondria are parts of cells that have their own DNA, as well as a fundamental role in metabolism. They are essential for animal life. With advances in DNA sequencing it has recently been shown that some individuals may possess multiple, distinct lineages of mitochondria in their cells. This suggests that the presence of multiple types of mitochondria, a condition known as heteroplasmy, may be an integral part of the evolution of many species. This finding is very surprising, because mitochondria, almost always are inherited from the mother only, and in humans, heteroplasmy has been linked to severe genetic disease. From an evolutionary perspective, the presence of more than one type of mitochondria in an individual may have an important function in generating genetic diversity. It is likely that the presence of multiple types of mitochondria presents opportunities to exchange genes between different mitochondrial lineages. Despite growing recognition of the potential significance of heteroplasmy, this aspect of animal evolution remains poorly understood. This project aims to address key questions relating to how heteroplasmy is generated, how long it can be maintained, and whether genes are exchanged between mitochondrial lineages. The bed bug will be used as a model species for these studies because it exhibits unusually high levels of heteroplasmy. Experiments to resolve these questions have the potential to fundamentally change how we look at genetic inheritance of mitochondrial DNA in animals. The project will include training of undergraduate and post-doctoral scholars, the establishment of a collaborative network of researchers and pest control operators, and public outreach in both Oklahoma and North Carolina. Furthermore, given that the bed bug is a significant public health concern, establishing it as a model system will continue to bring them to public attention, reinforcing awareness of the species.While uniparental inheritance appears to predominate in the animal kingdom, the growing evidence of heteroplasmy through paternal leakage and compelling recent evidence of mtDNA recombination, underscores that while we have developed a great understanding of mitochondrial function and evolution, our understanding of mitochondrial inheritance is far from complete. The bed bug, Cimex lectularius, is an ectoparasite that has seen an unprecedented resurgence in recent years. Studies have revealed that it exhibits high levels of mtDNA heteroplasmy, which is both pervasive and rapidly generated. Furthermore, mtDNA recombination appears common. Given the suitability and tractability of this species as a model system, this study will: (1) Address how intra- and inter-population genetic characteristics correlate with rates of heteroplasmy; (2) Investigate the degree to which mitogenomic divergence and mitonuclear interactions affect the rate of paternal leakage; (3) Empirically and theoretically examine heteroplasmy decay in a species where it is common and pervasive and for which genetic drift vs. selection may be evaluated; and (4) Take a complete mitogenomic approach to investigate recombination and the presence of recombination hotspots. Due to the high rate of leakage and recombination seen in the bed bug in concert with recent advances in DNA sequencing technology and analytical methods, this system offers a unique opportunity to address this hotly debated and evolutionarily consequential question.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

线粒体是细胞的一部分，它有自己的DNA，在新陈代谢中起着重要作用。它们是动物生命所必需的。随着DNA测序技术的进步，最近有研究表明，一些个体的细胞中可能具有多个不同的线粒体谱系。这表明，多种类型线粒体的存在，一种被称为异质性的情况，可能是许多物种进化的一个组成部分。这一发现非常令人惊讶，因为线粒体几乎总是只遗传自母亲，而在人类中，异质性与严重的遗传疾病有关。从进化的角度来看，个体中存在不止一种类型的线粒体可能对产生遗传多样性具有重要作用。多种类型线粒体的存在很可能为不同线粒体谱系之间的基因交换提供了机会。尽管越来越多的人认识到异质性的潜在意义，但动物进化的这一方面仍然知之甚少。该项目旨在解决与异质性是如何产生的，它可以维持多久，以及基因是否在线粒体谱系之间交换有关的关键问题。臭虫将被用作这些研究的模型物种，因为它表现出异常高的异质性。解决这些问题的实验有可能从根本上改变我们对动物线粒体DNA遗传的看法。该项目将包括培训本科生和博士后学者，建立研究人员和病虫害防治人员的合作网络，以及在俄克拉荷马州和北卡罗来纳州进行公众宣传。此外，鉴于臭虫是一个重大的公共卫生问题，将其建立为一个示范系统将继续引起公众的注意，加强对该物种的认识。虽然单亲遗传似乎在动物王国中占主导地位，但越来越多的证据表明，通过父系泄漏和最近令人信服的mtDNA重组的异质性，强调了尽管我们已经对线粒体功能和进化有了很大的了解，但我们对线粒体遗传的理解还远远不够。臭虫是一种体外寄生虫，近年来出现了前所未有的死灰复燃。研究表明，它表现出高水平的mtDNA异质性，这种异质性既普遍又迅速产生。此外，mtDNA重组似乎很常见。考虑到该物种作为模型系统的适用性和可追溯性，本研究将：(1)研究种群内和种群间遗传特征与异质性率的关系；(2)研究有丝分裂体差异和有丝核相互作用对父本漏卵率的影响程度；(3)从经验和理论上考察异质性衰变在一个物种中是常见的和普遍的，并且可以评估遗传漂变与选择；(4)采用完整的有丝分裂基因组方法研究重组和重组热点的存在。由于在臭虫中发现的高泄漏率和重组率以及DNA测序技术和分析方法的最新进展，该系统提供了一个独特的机会来解决这个激烈争论和进化上的重要问题。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Evolution: Bedbugs Evolved before Their Assumed Ancestral Host

进化：臭虫在其假定的祖先宿主之前进化

• DOI: 10.1016/j.cub.2019.06.025
• 发表时间: 2019
• 期刊: Current Biology
• 影响因子: 9.2
• 作者: Booth, Warren

Bed bugs, Cimex lectularius L., exhibiting metabolic and target site deltamethrin resistance are susceptible to plant essential oils

• DOI: 10.1016/j.pestbp.2020.104667
• 发表时间: 2020-10-01
• 期刊: PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
• 影响因子: 4.7
• 作者: Gaire, Sudip;Lewis, Cari D.;Gondhalekar, Ameya D.
• 通讯作者: Gondhalekar, Ameya D.

Recent Detection of Multiple Populations of the Tropical Bed Bug (Hemiptera: Cimicidae) Exhibiting kdr-Associated Mutations in Hawaii

• DOI: 10.1093/jme/tjaa022
• 发表时间: 2020-07-01
• 期刊: JOURNAL OF MEDICAL ENTOMOLOGY
• 影响因子: 2.1
• 作者: Lewis, Cari D.;Levine, Brenna A.;Booth, Warren
• 通讯作者: Booth, Warren

Decade long upsurge in mutations associated with pyrethroid resistance in bed bug populations in the USA

• DOI: 10.1007/s10340-022-01505-4
• 发表时间: 2022-04-20
• 期刊: JOURNAL OF PEST SCIENCE
• 影响因子: 4.8
• 作者: Lewis，Cari D.;Levine，Brenna A.;Booth，Warren
• 通讯作者: Booth，Warren

Knockdown Resistance-Associated Mutations Dominate Populations of the Common Bed Bug (Hemiptera: Cimicidae) Across the South Central United States

• DOI: 10.1093/jme/tjz105
• 发表时间: 2019-11-01
• 期刊: JOURNAL OF MEDICAL ENTOMOLOGY
• 影响因子: 2.1
• 作者: Holleman, Jeffrey G.;Robison, Grant A.;Booth, Warren
• 通讯作者: Booth, Warren