Linardopoulou Elena V, Williams Eleanor M, Fan Yuxin, Friedman Cynthia, Young Janet M, Trask Barbara J
Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North C3-168, Seattle, Washington 98109, USA.
Nature. 2005 Sep 1;437(7055):94-100. doi: 10.1038/nature04029.
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.
人类亚端粒是染色体末端染色体间节段性重复的多态性拼凑物。我们在此提供证据表明，这些拼凑物是近期通过染色体末端之间的反复易位产生的。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。一旦亚端粒重复出现，如相邻区域不一致的系统发育关系所示，它们就容易发生基于同源性的序列转移。亚端粒的染色体间重组是近期变化的一股强大力量。细胞遗传学和序列分析表明，在灵长类动物进化过程中，亚端粒拼凑物的片段改变位置和拷贝数的频率空前。已知亚端粒序列的一半是近期通过人类特异性序列转移和重复形成的。亚端粒动态变化导致基因重复率显著高于基因组平均水平，在人类生物学中可能产生有利和病理后果。更普遍地说，我们的分析表明了节段性多态性与基因组重排之间的一个进化循环。
