Dayama Gargi, Emery Sarah B, Kidd Jeffrey M, Mills Ryan E
Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Nucleic Acids Res. 2014 Nov 10;42(20):12640-9. doi: 10.1093/nar/gku1038. Epub 2014 Oct 27.
The transfer of mitochondrial genetic material into the nuclear genomes of eukaryotes is a well-established phenomenon that has been previously limited to the study of static reference genomes. The recent advancement of high throughput sequencing has enabled an expanded exploration into the diversity of polymorphic nuclear mitochondrial insertions (NumtS) within human populations. We have developed an approach to discover and genotype novel Numt insertions using whole genome, paired-end sequencing data. We have applied this method to a thousand individuals in 20 populations from the 1000 Genomes Project and other datasets and identified 141 new sites of Numt insertions, extending our current knowledge of existing NumtS by almost 20%. We find that recent Numt insertions are derived from throughout the mitochondrial genome, including the D-loop, and have integration biases that differ in some respects from previous studies on older, fixed NumtS in the reference genome. We determined the complete inserted sequence for a subset of these events and have identified a number of nearly full-length mitochondrial genome insertions into nuclear chromosomes. We further define their age and origin of insertion and present an analysis of their potential impact to ongoing studies of mitochondrial heteroplasmy and disease.
线粒体遗传物质转移到真核生物的核基因组中是一种既定现象，此前仅限于对静态参考基因组的研究。高通量测序技术的最新进展使得对人类群体中多态性核线粒体插入序列（NumtS）的多样性进行更广泛的探索成为可能。我们开发了一种利用全基因组双端测序数据发现新的Numt插入并进行基因分型的方法。我们将此方法应用于来自千人基因组计划的20个群体中的1000个人以及其他数据集，鉴定出141个新的Numt插入位点，使我们对现有NumtS的当前认知扩展了近20%。我们发现，近期的Numt插入源自线粒体基因组的各个区域，包括D环，并且其整合偏向在某些方面与先前对参考基因组中较古老、固定的NumtS的研究有所不同。我们确定了这些事件中的一部分的完整插入序列，并鉴定出一些几乎全长的线粒体基因组插入到核染色体中的情况。我们进一步确定了它们的插入年龄和起源，并对它们对正在进行的线粒体异质性和疾病研究的潜在影响进行了分析。
