Giordano Joti, Ge Yongchao, Gelfand Yevgeniy, Abrusán György, Benson Gary, Warburton Peter E
Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA.
PLoS Comput Biol. 2007 Jul;3(7):e137. doi: 10.1371/journal.pcbi.0030137.
The constant bombardment of mammalian genomes by transposable elements (TEs) has resulted in TEs comprising at least 45% of the human genome. Because of their great age and abundance, TEs are important in comparative phylogenomics. However, estimates of TE age were previously based on divergence from derived consensus sequences or phylogenetic analysis, which can be unreliable, especially for older more diverged elements. Therefore, a novel genome-wide analysis of TE organization and fragmentation was performed to estimate TE age independently of sequence composition and divergence or the assumption of a constant molecular clock. Analysis of TEs in the human genome revealed approximately 600,000 examples where TEs have transposed into and fragmented other TEs, covering >40% of all TEs or approximately 542 Mbp of genomic sequence. The relative age of these TEs over evolutionary time is implicit in their organization, because newer TEs have necessarily transposed into older TEs that were already present. A matrix of the number of times that each TE has transposed into every other TE was constructed, and a novel objective function was developed that derived the chronological order and relative ages of human TEs spanning >100 million years. This method has been used to infer the relative ages across all four major TE classes, including the oldest, most diverged elements. Analysis of DNA transposons over the history of the human genome has revealed the early activity of some MER2 transposons, and the relatively recent activity of MER1 transposons during primate lineages. The TEs from six additional mammalian genomes were defragmented and analyzed. Pairwise comparison of the independent chronological orders of TEs in these mammalian genomes revealed species phylogeny, the fact that transposons shared between genomes are older than species-specific transposons, and a subset of TEs that were potentially active during periods of speciation.
转座元件（TEs）对哺乳动物基因组的持续轰击已导致TEs占人类基因组的比例至少达到45%。由于TEs存在的时间久远且数量众多，它们在比较系统发育基因组学中具有重要意义。然而，此前对TEs年代的估计是基于与推导的共有序列的差异或系统发育分析，而这些方法可能并不可靠，尤其是对于年代久远且差异较大的元件。因此，开展了一项全新的全基因组范围内的TEs组织和片段化分析，以独立于序列组成、差异或恒定分子钟假设来估计TEs的年代。对人类基因组中的TEs分析发现，大约有60万个TEs转座并插入到其他TEs中并使其片段化的例子，覆盖了所有TEs的40%以上，即约542兆碱基对的基因组序列。这些TEs在进化时间上的相对年代隐含在它们的组织中，因为较新的TEs必然是转座到已存在的较老的TEs中。构建了一个矩阵，记录每个TEs插入到其他每个TEs中的次数，并开发了一个新的目标函数，得出了跨越1亿多年的人类TEs的时间顺序和相对年代。该方法已被用于推断所有四大类主要TEs的相对年代，包括最古老、差异最大的元件。对人类基因组历史上DNA转座子的分析揭示了一些MER2转座子的早期活性，以及MER1转座子在灵长类谱系中相对较新的活性。对另外六个哺乳动物基因组中的TEs进行了片段化和分析。对这些哺乳动物基因组中TEs独立时间顺序的成对比较揭示了物种系统发育，基因组间共享的转座子比物种特异性转座子更古老这一事实，以及在物种形成时期可能活跃的一部分TEs。
