Evidence that two reports of mtDNA cytochrome c oxidase "mutations" in Alzheimer's disease are based on nDNA pseudogenes of recent evolutionary origin
Evidence that two reports of mtDNA cytochrome c oxidase "mutations" in Alzheimer's disease are based on nDNA pseudogenes of recent evolutionary origin
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DOI：
10.1006/bbrc.1998.8353
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发表时间：
1998-03-27
影响因子：
3.1
通讯作者：
Parker, WD
中科院分区：
文献类型：
--
作者：
Davis, JN;Parker, WD
最近，两份报告[R.E.Davis et al.(1997)会议过程。娜塔莉。阿卡德。SCI。美国94,4564-4569和E.Fahy等人。(1997)Nucleic Ids Res.253102-3109]描述了编码两个细胞色素C氧化酶亚单位(CO1和CO2)的基因中的一系列异质线粒体DNA(MtDNA)突变，这两个亚单位在阿尔茨海默病患者中分离得比对照组更高。使用线粒体DNA缺失的NT2细胞，我们提供了进一步的证据，证明这两个报告是错误的，基于从编码线粒体DNA的假基因(线粒体DNA Psi S)的核DNA扩增产生的聚合酶链式反应伪影。我们的发现与最近对这些假定的mtDNA Psi序列的其他研究相似，但并不完全相同。这种序列的可变性可能表明多个线粒体DNA Psi S参与其中，他们都是较新的进化起源。虽然这种伪基因很有趣，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发挥任何作用。(C)1998年学术出版社。
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. (C) 1998 Academic Press.