Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication
Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication
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DOI：
10.1038/nature04029
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发表时间：
2005-09-01
期刊：
影响因子：
64.8
通讯作者：
Trask, BJ
中科院分区：
文献类型：
--
作者：
Linardopoulou, EV;Williams, EM;Trask, BJ
人类亚端粒是染色体末端的染色体间片段复制的多态性拼凑物。在这里，我们提供的证据表明，这些拼凑最近出现的染色体末端之间的重复易位。我们评估了异位DNA修复的主要机制对亚端粒重复形成的相对贡献，发现非同源末端连接占主导地位。一旦亚端粒重复出现，它们容易发生基于同源性的序列转移，如相邻部分的不一致的系统发育关系所示。亚端粒的染色体间重组是最近变化的一个强大力量。细胞遗传学和序列分析表明，在灵长类动物进化过程中，端粒下的碎片以前所未有的频率改变了位置和拷贝数。已知的亚端粒序列中有一半是最近通过人类特异性序列转移和复制形成的。亚端粒动力学导致基因复制率显著高于基因组平均水平，并且可能在人类生物学中具有有利和病理性的后果。更一般地说，我们的分析表明，片段多态性和基因组重排之间的进化周期。
Human subtelomeres are polymorphic patchworks of interchromosomal segmental duplications at the ends of chromosomes. Here we provide evidence that these patchworks arose recently through repeated translocations between chromosome ends. We assess the relative contribution of the principal mechanisms of ectopic DNA repair to the formation of subtelomeric duplications and find that non-homologous end-joining predominates. Once subtelomeric duplications arise, they are prone to homology-based sequence transfers as shown by the incongruent phylogenetic relationships of neighbouring sections. Interchromosomal recombination of subtelomeres is a potent force for recent change. Cytogenetic and sequence analyses reveal that pieces of the subtelomeric patchwork have changed location and copy number with unprecedented frequency during primate evolution. Half of the known subtelomeric sequence has formed recently, through human-specific sequence transfers and duplications. Subtelomeric dynamics result in a gene duplication rate significantly higher than the genome average and could have both advantageous and pathological consequences in human biology. More generally, our analyses suggest an evolutionary cycle between segmental polymorphisms and genome rearrangements.