Jansen R P
Sydney IVF and the University of Sydney, Australia.
Hum Reprod. 2000 Jul;15 Suppl 2:1-10. doi: 10.1093/humrep/15.suppl_2.1.
The mitochondrial genome comprises a circular, histone-free 'chromosome' of 16.6 kb of DNA, present in one or more copies in every mitochondrion. This chromosome has been tightly conserved for more than half a billion years, coding in every multicellular animal so far investigated, both vertebrate and invertebrate: (i) the same 13 protein subunits required for oxidative phosphorylation; (ii) a component of each of the two mitochondrial ribosome subunits; and (iii) the 22 transport RNAs present within the mitochondrion. Exons on the circle are tightly packed, with no spacing introns. Mitochondrial DNA is histone-free, has limited repair ability, and has a relatively high mutation-fixation rate. Inheritance is cytoplasmic and maternal, with epidemiological evidence (namely the familial distribution of polymorphisms) indicating that recombination with mtDNA of paternal origin is exceedingly rare. Thus the maintenance and evolution of mtDNA (its remarkably successful symbiotic persistence with the nuclear genome) has been essentially asexual. The machinery for homologous recombination is present in mitochondria of at least some species, however, and it might be surprising if it did not occur between circles in some circumstances. By bringing together the fields of mitochondrial biochemistry, evolutionary genetics, reproductive physiology, and neuromuscular medicine in focusing on the inheritance of normal and abnormal human mtDNA, we can hope to better understand the forces behind this genome's inheritance and what might be required of ovarian function to satisfy its accurate persistence over millions of years. Clinically we can hope also for a better understanding of ooplasmic factors in human fertility and in the wide manifestations of mitochondrial genomic disease.
线粒体基因组由一个16.6 kb的环状、无组蛋白的DNA“染色体”组成，每个线粒体中存在一个或多个拷贝。这条染色体在超过5亿年的时间里一直被严格保守，在迄今研究的每一种多细胞动物中都有编码，包括脊椎动物和无脊椎动物：（i）氧化磷酸化所需的相同的13种蛋白质亚基；（ii）两个线粒体核糖体亚基各自的一个组分；以及（iii）线粒体中存在的22种转运RNA。环上的外显子紧密排列，没有间隔内含子。线粒体DNA无组蛋白，修复能力有限，且突变固定率相对较高。遗传是细胞质遗传和母系遗传，流行病学证据（即多态性的家族分布）表明，与父源线粒体DNA的重组极为罕见。因此，线粒体DNA的维持和进化（它与核基因组极为成功的共生存续）基本上是无性的。然而，至少在一些物种的线粒体中存在同源重组机制，如果在某些情况下环之间不发生重组，那可能会令人惊讶。通过将线粒体生物化学、进化遗传学、生殖生理学和神经肌肉医学等领域结合起来，聚焦于正常和异常人类线粒体DNA的遗传，我们有望更好地理解该基因组遗传背后的力量，以及卵巢功能需要满足哪些条件才能确保其在数百万年的时间里准确存续。在临床上，我们也有望更好地理解人类生育中的卵质因素以及线粒体基因组疾病的广泛表现。
