Insertion of telomeric repeats at intrachromosomal break sites during primate evolution
Insertion of telomeric repeats at intrachromosomal break sites during primate evolution
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DOI：
10.1101/gr.2778904
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发表时间：
2004-09-01
期刊：
影响因子：
7
通讯作者：
Giulotto, E
中科院分区：
文献类型：
--
作者：
Nergadze, SG;Rocchi, M;Giulotto, E
在远离染色体末端的地方发现了类似端粒的 DNA 短块（间质端粒序列，ITS）。我们通过比较 10 个人类 ITS 的基因座与 12 个灵长类动物的基因组直向同源物，解决了此类序列如何产生的问题。 ITS 并非像其他微卫星那样源自先前存在的 TTAGGG 单元的扩展，而是在进化过程中突然出现。沿着灵长类进化树，有九次插入事件的年代在 40 至 600 万年前之间。序列比较表明，在每种情况下，(TTAGGG)(n) DNA 块都是双链断裂修复的结果。事实上，祖先序列要么被端粒样重复序列精确中断，要么显示出在双链断裂修复位点观察到的典型修饰，例如短删除、随机序列的添加或重复。对黑猩猩特异性 ITS 的分析也得出了类似的结论。我们建议通过在断裂位点捕获端粒 DNA 片段或通过端粒酶插入端粒序列。我们的结论表明，人类智能交通系统是古代破坏的遗迹，而不是像之前所认为的那样脆弱的遗址本身。
Short blocks of telomeric-like DNA (interstitial Telomeric Sequences, ITSs) are found far from chromosome ends. We addressed the question as to how Such Sequences arise by comparing the loci of 10 human ITSs with their genomic orthologs in 12 primate species. The ITSs did not derive from expansion of pre-existing TTAGGG units, as described for other microsatellites, but appeared suddenly during evolution. Nine insertion events were dated along the primate evolutionary tree, the dates ranging between 40 and 6 million years ago. Sequence comparisons suggest that in each case the block of (TTAGGG)(n) DNA arose as a result of double-strand break repair. In fact, ancestral sequences were either interrupted precisely by the tract of telomeric-like repeats or showed the typical modifications observed at double-strand break repair sites Such as short deletions, addition of random sequences, or duplications. Similar conclusions were drawn from the analysis of a chimpanzee-specific ITS. We propose that telomeric sequences were inserted by the capture of a telomeric DNA fragment at the break site or by the telomerase enzyme. Our conclusions indicate that human ITSs are relics of ancient breakage rather than fragile sites themselves, as previously suggested.