Mutation hot spots in mammalian mitochondrial DNA
Mutation hot spots in mammalian mitochondrial DNA
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DOI：
10.1101/gr.4305906
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发表时间：
2006-02-01
期刊：
影响因子：
7
通讯作者：
Belkhir, K
中科院分区：
文献类型：
--
作者：
Galtier, N;Enard, D;Belkhir, K
动物线粒体DNA的特征是具有显著高水平的种内同源性，即分子位点之间的系统发育不一致。一些研究人员援引重组来解释它，挑战动物中母系克隆线粒体遗传的教条。或者，高度的同源性可以用突变热点的存在来解释。通过使用详尽的哺乳动物数据集，我们测试的热点假说，通过比较模式的位点特异性多态性和分歧，在几组密切相关的物种，包括人科动物。我们检测到显着的同义多态性密切相关的物种在不同的哺乳动物群体之间的共同发生，以及在人类（一方面）和Hominoidea物种（另一方面）之间的特定位点的变异水平之间的相关性，表明突变热点实际上存在于哺乳动物线粒体编码区。然而，整个数据不能用简单的突变热点模型来解释。相反，我们表明位点特异性突变率随时间迅速变化，因此相同的位点在不同的谱系中不是超变的。这项研究提供了一个合理的突变模型，可能占线粒体序列变异在哺乳动物中的特殊分布，而不需要调用重组。它还提示了人类线粒体位点特异性超变的近端原因。
Animal mitochondrial DNA is characterized by a remarkably high level of within-species homoplasy, that is, phylogenetic incongruence between sites of the molecule. Several investigators have invoked recombination to explain it, challenging the dogma of maternal, clonal mitochondrial inheritance in animals. Alternatively, a high level of homoplasy Could be explained by the existence of mutation hot spots. By using an exhaustive mammalian data set, we test the hot spot hypothesis by comparing patterns of site-specific polymorphism and divergence in several groups of closely related species, including hominids. We detect significant co-occurrence of synonymous polymorphisms among closely related species in various mammalian groups, and a correlation between the site-specific levels of variability within humans (on one hand) and between Hominoidea species (on the other hand), indicating that mutation hot spots actually exist in mammalian mitochondrial coding regions. The whole data, however, cannot be explained by a simple mutation hot spots model. Rather, we show that the site-specific Mutation rate quickly varies in time, so that the same sites are not hypermutable in distinct lineages. This Study provides a plausible mutation model that potentially accounts for the peculiar distribution of mitochondrial sequence variation in mammals without the need for invoking recombination. It also gives hints about the proximal causes of mitochondrial site-specific hypermutability in humans.