Shuffling of genes within low-copy repeats on 22qll (LCR22) by Alu-mediated recombination events during evolution
Shuffling of genes within low-copy repeats on 22qll (LCR22) by Alu-mediated recombination events during evolution
复制标题
DOI：
10.1101/gr.1549503
复制
发表时间：
2003-12-01
期刊：
影响因子：
7
通讯作者：
Morrow, BE
中科院分区：
文献类型：
--
作者：
Babcock, M;Pavlicek, A;Morrow, BE
低拷贝重复序列或片段重复是基因组中高度动态的区域。染色体22q11.2上的低拷贝重复序列（LCR 22）是由重复过程形成的基因和假基因的复杂镶嵌体;它们介导与腭心面综合征/DiGeorge综合征、der（22）综合征和猫眼综合征相关的染色体重排。追踪重组事件的底物和产物的能力为鉴定负责形成LCR 22的机制提供了独特的机会。我们研究了已知的LCR 22基因及其重复衍生物的基因组序列。我们在底物的断裂点和USP 18、GGT和GGTLA重组的截短产物的连接点发现了Alu（SINE）元素，这与ESTA介导的不平等交换事件一致。此外，我们能够追踪lpl3.1上的IGSF 3和22q11.2上的GGT之间的可能的染色体间融合。断裂点发生在Alu元件内部以及它们的5'或3'端。5'或3'末端重排的可能刺激可能是不同Alu元件之间的高序列相似性，以及位于Alu元件侧翼的逆转录转座子靶位点重复的潜在重组作用，其含有潜在的可扭结DNA位点。这些位点可能代表重组的焦点。因此，在灵长类动物进化过程中，由基因组重排介导的基因组改组有助于基因组结构。
Low-copy repeats, or segmental duplications, are highly dynamic regions in the genome. The low-copy repeats on chromosome 22qll.2 (LCR22) are a complex mosaic of genes and pseudogenes formed by duplication processes; they mediate chromosome rearrangements associated with velo-cardio-facial syndrome/DiGeorge syndrome, der(22) syndrome, and cat-eye syndrome. The ability to trace the substrates and products of recombination events provides a unique opportunity to identify the mechanisms responsible for shaping LCR22s. We examined the genomic sequence of known LCR22 genes and their duplicated derivatives. We found Alu (SINE) elements at the breakpoints in the substrates and at the junctions in the truncated products of recombination for USP18, GGT, and GGTLA, consistent with Alu-mediated unequal crossing-over events. In addition, we were able to trace a likely interchromosomal Alu-mediated fusion between IGSF3 on lpl3.1 and GGT on 22qll.2. Breakpoints occurred inside Alu elements as well as in the 5' or 3' ends of them. A possible stimulus for the 5' or 3' terminal rearrangements may be the high sequence similarities between different Alu elements, combined with a potential recombinogenic role of retrotransposon target-site duplications flanking the Alu element, containing potentially kinkable DNA sites. Such sites may represent focal points for recombination. Thus, genome shuffling by Alu-mediated rearrangements has contributed to genome architecture during primate evolution.