Davis J N, Parker W D
Center for the Study of Neurodegenerative Diseases, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Biochem Biophys Res Commun. 1998 Mar 27;244(3):877-83. doi: 10.1006/bbrc.1998.8353.
Recently, two reports [R. E. Davis et al. (1997) Proc. Natl. Acad. Sci. USA 94, 4564-4569 and E. Fahy et al. (1997) Nucleic Acids Res. 25, 3102-3109] described a series of heteroplasmic mitochondrial DNA (mtDNA) mutations in the genes encoding two cytochrome c oxidase subunits (CO1 and CO2) which segregated in higher abundance with Alzheimer's disease subjects than controls. Using mtDNA-depleted NT2 cells, we provide further evidence that these two reports are erroneously based on a PCR artifact arising from the amplification of nuclear DNA encoded mtDNA pseudogenes (mtDNA psi s). Our findings are similar, but not identical, to other recent studies of these putative mtDNA psi sequences. This sequence variability may indicate that multiple mtDNA psi s, all of comparatively recent evolutionary origin are involved. While such pseudogenes are interesting in that they provide a molecular evolutionary "snapshot" of human ancestral mtDNA, it is unlikely that they play any role in the etiology of Alzheimer's disease.
最近，两份报告[R. E. 戴维斯等人（1997年），《美国国家科学院院刊》94卷，4564 - 4569页；E. 法希等人（1997年），《核酸研究》25卷，3102 - 3109页]描述了一系列异质性线粒体DNA（mtDNA）突变，这些突变发生在编码两个细胞色素c氧化酶亚基（CO1和CO2）的基因中，在阿尔茨海默病患者中比在对照组中以更高的丰度分离。利用mtDNA缺失的NT2细胞，我们提供了进一步的证据，表明这两份报告错误地基于由核DNA编码的mtDNA假基因（mtDNA ψs）扩增产生的PCR假象。我们的发现与最近对这些假定的mtDNA ψ序列的其他研究相似，但并不相同。这种序列变异性可能表明涉及多个相对近期进化起源的mtDNA ψs。虽然这类假基因很有趣，因为它们提供了人类祖先mtDNA的分子进化“快照”，但它们不太可能在阿尔茨海默病的病因学中起任何作用。
