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

线粒体是细胞的一部分，有自己的DNA，以及在新陈代谢中的基本作用。 它们对动物的生活至关重要。随着DNA测序的进展，最近已经表明，一些个体可能在其细胞中拥有多个不同的线粒体谱系。 这表明，存在多种类型的线粒体，这种情况被称为异质性，可能是许多物种进化的一个组成部分。 这一发现是非常令人惊讶的，因为线粒体几乎总是只从母亲那里遗传，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功能。 多种类型的线粒体的存在可能为不同线粒体谱系之间的基因交换提供了机会。尽管人们越来越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。该项目旨在解决与异质性如何产生，可以维持多久以及线粒体谱系之间是否交换基因有关的关键问题。臭虫将被用作这些研究的模式物种，因为它表现出异常高水平的异质性。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，建立研究人员和害虫控制人员的合作网络，以及在俄克拉荷马州和北卡罗来纳州开展公众宣传。此外，鉴于臭虫是一个重大的公共卫生问题，将其建立为一个模型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，通过父系泄漏和线粒体DNA重组的令人信服的最新证据，强调虽然我们已经对线粒体功能和进化有了很好的了解，但我们对线粒体遗传的理解还远远没有完成。臭虫，温带臭虫，是一种体外寄生虫，近年来出现了前所未有的复苏。研究表明，它表现出高水平的mtDNA异质性，这是普遍和快速产生。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用性和易处理性，本研究将：（1）解决种群内和种群间遗传特征与异质性率的相关性;（2）调查有丝分裂基因组分歧和线粒体相互作用影响父本泄漏率的程度;（3）从经验和理论上研究一个物种中的异质性衰退，在那里它是常见和普遍的，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学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，该系统为解决这一激烈辩论和进化后果的问题提供了一个独特的机会。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。

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.