Inheritance of mitochondrial DNA recombinants in double-heteroplasmic families: potential implications for phylogenetic analysis.
Inheritance of mitochondrial DNA recombinants in double-heteroplasmic families: potential implications for phylogenetic analysis.
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双异质家族中线粒体 DNA 重组体的遗传：对系统发育分析的潜在影响。
DOI：
10.1086/511282
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发表时间：
2007
影响因子：
9.8
通讯作者：
Kunz,WolframS
中科院分区：
文献类型：
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作者：
Zsurka,Gábor;Hampel,KevinG;Kudina,Tatiana;Kornblum,Cornelia;Kraytsberg,Yevgenia;Elger,ChristianE;Khrapko,Konstantin;Kunz,WolframS
近年来，在骨骼肌中发现了人线粒体DNA的体细胞重组。为了确定重组mtDNA分子是否可以通过胚系传播，我们调查了两个家族，每个家族都有两个遗传的异质性mtDNA突变。利用等位基因特异性聚合酶链式反应以及单细胞和单分子突变分析，我们在两个家族中发现了两个异质突变(四质体)的所有四种可能的等位基因组合，这是mtDNA重组的标志。我们强烈地认为，这些重组mtDNA分子是遗传的，而不是从身体上产生的，因为它们(1)高度丰富，(2)存在于与母亲相关的家庭成员的不同组织中，包括年轻的个体。此外，将其中一个家族的完整mtDNA序列与数据库序列进行比较，发现了一种不规则的、非树状的突变模式，让人想起网状结构。因此，我们提出，人类线粒体DNA系统发育树的某些网状结构可以通过共存的携带多种突变的线粒体DNA分子的重组来解释。
Recently, somatic recombination of human mitochondrial DNA (mtDNA) was discovered in skeletal muscle. To determine whether recombinant mtDNA molecules can be transmitted through the germ line, we investigated two families, each harboring two inherited heteroplasmic mtDNA mutations. Using allele-specific polymerase chain reaction and single-cell and single-molecule mutational analyses, we discovered, in both families, all four possible allelic combinations of the two heteroplasmic mutations (tetraplasmy), the hallmark of mtDNA recombination. We strongly suggest that these recombinant mtDNA molecules were inherited rather than de novo generated somatically, because they (1) are highly abundant and (2) are present in different tissues of maternally related family members, including young individuals. Moreover, the comparison of the complete mtDNA sequence of one of the families with database sequences revealed an irregular, nontreelike pattern of mutations, reminiscent of a reticulation. We therefore propose that certain reticulations of the human mtDNA phylogenetic tree might be explained by recombination of coexisting mtDNA molecules harboring multiple mutations.