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: 1754254
• 负责人: Bruce Rannala
• 金额: $ 15.03万
• 依托单位: University of California-Davis
• 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 2022-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1754254&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，拥有自己的DNA，在新陈代谢中起着基础性的作用。它们对动物的生活是必不可少的。随着DNA测序的进步，最近有研究表明，一些个体可能在他们的细胞中拥有多个不同的线粒体谱系。这表明，多种类型线粒体的存在，即所谓的异质性，可能是许多物种进化过程中不可或缺的一部分。这一发现非常令人惊讶，因为线粒体几乎总是只从母亲那里遗传过来的，而在人类中，异质性与严重的遗传病有关。从进化论的角度来看，个体中存在一种以上类型的线粒体可能在产生遗传多样性方面具有重要作用。多种类型线粒体的存在很可能提供了在不同线粒体谱系之间交换基因的机会。尽管人们越来越多地认识到异质性的潜在意义，但对动物进化的这一方面仍然知之甚少。这个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等关键问题。臭虫将被用作这些研究的模式物种，因为它表现出不同寻常的高度异质性。解决这些问题的实验有可能从根本上改变我们看待动物线粒体DNA遗传的方式。该项目将包括培训本科生和博士后学者，建立研究人员和虫害防治操作员的合作网络，以及在俄克拉荷马州和北卡罗来纳州进行公众宣传。此外，鉴于床虱是一个重大的公共卫生问题，建立它作为一个模式系统将继续使它们引起公众的注意，加强对物种的认识。虽然单亲遗传似乎在动物界占主导地位，但越来越多的证据表明，由于父亲的泄漏而产生的异质性，以及最近令人信服的mtDNA重组证据，突显出尽管我们已经对线粒体的功能和进化有了很好的理解，但我们对线粒体遗传的理解还远远不完整。臭虫Cimex lectularius是一种体外寄生虫，近年来出现了前所未有的卷土重来。研究表明，它表现出高度的线粒体DNA异质性，这种异质性既普遍又迅速产生。此外，线粒体DNA重组似乎很常见。鉴于该物种作为模式系统的适宜性和易操纵性，本研究将：(1)解决种群内和种群间的遗传特征如何与异质性比率相关；(2)调查有丝分裂和有丝分裂相互作用对父本渗漏率的影响程度；(3)从经验和理论上研究异质性衰退，在该物种中，异质性是常见的和普遍的，其遗传漂移和选择可以被评估；以及(4)采用完整的有丝分裂组学方法来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与DNA测序技术和分析方法的最新进步相一致，该系统提供了一个独特的机会来解决这个激烈辩论和进化结果的问题。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。