Genetic basis of sperm mitochondrial elimination

线粒体是细胞的组成部分，其产生用于为关键过程提供动力的能量分子， 维持生命。在受精过程中，大多数有性生殖的生物，比如人类， 每一位家长。线粒体有自己的DNA基因组，编码蛋白质负责 产生这种细胞能量。然而，现有的生物学范式是，大多数物种的后代， 包括人类在内，线粒体不是从父母双方获得，而是仅从母亲获得。这建立 线粒体DNA中破坏能量产生的突变从受影响的 所有孩子的母亲在受精时。精子也含有线粒体，但它们通常不是 传给后代。关于鸡蛋是否具有识别和破坏的成分， 精子线粒体和/或精子是否在受精前启动其自身的线粒体自毁。 虽然我们对线粒体如何产生能量了解很多，但对线粒体的这一过程却知之甚少。 父系线粒体消除，包括所有分子成分的身份，以及是否和 卵母细胞是如何区分精子线粒体的该项目的长期目标是确定 父系线粒体消除的遗传和分子基础。有趣的是，之前的研究 表明父系线粒体消除在某些物种的杂交中不会有效地发生， 这表明在这些物种中父系线粒体传递的遗传作图作为识别 参与父系线粒体消除的基因。作为这个项目的一部分，现有的动物模型的杂交 将生成系统并针对父体线粒体的存在进行表型分析。现有基因型数据 将沿着表型数据进行分析，以绘制涉及父本的基因座。 线粒体传递在一种补充方法中，将产生新的混合体，以评估如何 在该系统中广泛存在父系线粒体传递。另外，现有的性别决定 突变体将被用来解决精子是否固有地产生自己的信号， 精子携带线粒体，或者该信号的产生是否由雄性体细胞组织指导。成果 这项研究项目的直接相关的通知政策决定使用三亲 受精和其他临床干预措施，以规避母体线粒体遗传， 诊断人类遗传性线粒体遗传疾病。

Mitochondria are components of cells that generate molecules of energy used to power critical processes that sustain life. At fertilization, most sexually reproducing organisms, like humans, obtain half of their genes from each parent. Mitochondria have their own DNA genomes, which encode the proteins responsible for the generation of that cellular energy. However, the existing paradigm in biology is that offspring in most species, including humans, obtain their mitochondria not from both parents but only from the mother. This establishes the situation where mutations in mitochondrial DNA that disrupt energy production are passed from affected mothers to all of their children at fertilization. Sperm contain mitochondria as well, but they are not normally passed on to offspring. Consensus is weak on whether eggs have components that recognize and destroy sperm mitochondria and/or whether sperm initiate their own mitochondrial self-destruction prior to fertilization. Although much is known about how mitochondria produce energy, much less is known about this process of paternal mitochondrial elimination, including the identities of all of the molecular components and whether and how oocytes distinguish sperm mitochondria from their own. The long term objective of this project is to identify the genetic and molecular basis of paternal mitochondrial elimination. Interestingly, previous studies have suggested that paternal mitochondrial elimination does not occur effectively in hybrids of some species, suggesting genetic mapping of paternal mitochondrial transmission in those species as a method for identifying genes involved in paternal mitochondrial elimination. As part of this project, existing hybrids of an animal model system will be generated and phenotyped for the presence of paternal mitochondria. Existing genotype data from those hybrids will be analyzed along with the phenotype data to map loci involved in paternal mitochondrial transmission. In a complementary approach, new hybrids will be generated to assess how widespread is paternal mitochondrial transmission in this system. Separately, existing sex determination mutants will be used to address the question whether sperm inherently generate their own signal that marks sperm-borne mitochondria, or whether production of that signal is directed by male somatic tissue. Outcomes of this research project are directly relevant to informing policy decisions about the use of three-parent fertilization and other clinical interventions for circumventing maternal mitochondrial inheritance and also to diagnosing heritable mitochondrial genetic disorders in humans.