Copy number evolution in simple and complex tandem repeats across the C57BL/6 and C57BL/10 inbred mouse lines.
Copy number evolution in simple and complex tandem repeats across the C57BL/6 and C57BL/10 inbred mouse lines.
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DOI：
10.1093/g3journal/jkab184
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发表时间：
2021-08-07
期刊：
影响因子：
--
通讯作者：
Clark AG
中科院分区：
文献类型：
--
作者：
Flynn JM;Brown EJ;Clark AG
简单序列串联重复序列是基因组中进化最快的部分之一。一些重复扩增与哺乳动物疾病或减数分裂分离扭曲有关，但不同世代之间拷贝数的变化速度尚不清楚。在这里，我们使用C57BL/6和C57BL/10近交系小鼠品系的14个不同的亚系，这两个品系已经独立进化了大约300代，以估计全基因组串联重复序列的拷贝数变化率。变化的速度在不同的重复和不同的线路上有所不同。值得注意的是，CAG在编码区的扩展与许多神经和遗传疾病有关，其拷贝数高度稳定，可能表明选择稳定。变异率与拷贝数呈正相关，但变化的方向和大小在不同的线上有所不同。在大多数简单重复中，一些小鼠品系经历了一致的损失或增加，但这与复杂重复中的拷贝数变化无关。按拷贝数归一化后，简单重复序列与较丰富的复杂重复序列的拷贝数变化率相似。最后，Y-特异性着丝粒重复序列的变化率是其他染色体上同源着丝粒重复序列的四倍。卫星复杂性的结构差异，或Y染色体的限制和男性生殖系突变率的提高，可能解释了较高的变化率。总体而言，我们的工作强调了长串联重复序列的突变流动性，以及全基因组串联重复之间的相关性和限制，这表明周转不是一个完全中性的过程。
Simple sequence tandem repeats are among the most rapidly evolving compartments of the genome. Some repeat expansions are associated with mammalian disease or meiotic segregation distortion, yet the rates of copy number change across generations are not well known. Here, we use 14 distinct sublineages of the C57BL/6 and C57BL/10 inbred mouse strains, which have been evolving independently over about 300 generations, to estimate the rates of copy number changes in genome-wide tandem repeats. Rates of change varied across repeats and across lines. Notably, CAG, whose expansions in coding regions are associated with many neurological and genetic disorders, was highly stable in copy number, likely indicating stabilizing selection. Rates of change were positively correlated with copy number, but the direction and magnitude of changes varied across lines. Some mouse lines experienced consistent losses or gains across most simple repeats, but this did not correlate with copy number changes in complex repeats. Rates of copy number change were similar between simple repeats and the more abundant complex repeats after normalization by copy number. Finally, the Y-specific centromeric repeat had a fourfold higher rate of change than the homologous centromeric repeat on other chromosomes. Structural differences in satellite complexity, or restriction to the Y chromosome and elevated mutation rates of the male germline, may explain the higher rate of change. Overall, our work underscores the mutational fluidity of long tandem arrays of repeats, and the correlations and constraints between genome-wide tandem repeats, which suggest that turnover is not a completely neutral process.
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影响因子：
7
作者：
Uchimura A;Higuchi M;Minakuchi Y;Ohno M;Toyoda A;Fujiyama A;Miura I;Wakana S;Nishino J;Yagi T
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