Department of Computational Biology, Graduate School of Frontier Science, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561, Japan.
Nucleic Acids Res. 2012 Oct;40(18):9073-88. doi: 10.1093/nar/gks424. Epub 2012 Jul 3.
It is well known that remnants of partial or whole copies of mitochondrial DNA, known as Nuclear MiTochondrial sequences (NUMTs), are found in nuclear genomes. Since whole genome sequences have become available, many bioinformatics studies have identified putative NUMTs and from those attempted to infer the factors involved in NUMT creation. These studies conclude that NUMTs represent randomly chosen regions of the mitochondrial genome. There is less consensus regarding the nuclear insertion sites of NUMTs - previous studies have discussed the possible role of retrotransposons, but some recent ones have reported no correlation or even anti-correlation between NUMT sites and retrotransposons. These studies have generally defined NUMT sites using BLAST with default parameters. We analyze a redefined set of human NUMTs, computed with a carefully considered protocol. We discover that the inferred insertion points of NUMTs have a strong tendency to have high-predicted DNA curvature, occur in experimentally defined open chromatin regions and often occur immediately adjacent to A + T oligomers. We also show clear evidence that their flanking regions are indeed rich in retrotransposons. Finally we show that parts of the mitochondrial genome D-loop are under-represented as a source of NUMTs in primate evolution.
众所周知，核基因组中存在线粒体 DNA 的部分或全部拷贝的残余物，称为核线粒体序列（NUMTs）。自从全基因组序列可用以来，许多生物信息学研究已经鉴定了假定的 NUMTs，并试图从这些序列中推断出 NUMT 产生的相关因素。这些研究得出的结论是，NUMTs 代表线粒体基因组中随机选择的区域。关于 NUMTs 的核插入位点的共识较少——先前的研究讨论了逆转录转座子的可能作用，但最近的一些研究报告称，NUMT 位点与逆转录转座子之间没有相关性，甚至存在负相关性。这些研究通常使用默认参数的 BLAST 来定义 NUMT 位点。我们使用精心考虑的协议重新分析了一组人类 NUMTs，发现 NUMTs 的推断插入点具有强烈的 DNA 弯曲预测倾向，出现在实验定义的开放染色质区域中，并且通常紧邻 A+T 寡聚物。我们还提供了明确的证据表明，它们的侧翼区域确实富含逆转录转座子。最后，我们表明，在灵长类动物进化过程中，线粒体基因组 D 环的某些部分作为 NUMTs 的来源被低估了。
