完整的人类中间体的变化和演变
Glennis A Logsdon1,2, Allison N Rozanski1, Fedor Ryabov3
1Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Nature
|April 3, 2024
概括
人类的中间体高度可变且难以测序. 新的研究揭示了显著的尺寸变化,新的重复结构和不同的动态位置,为中心体进化提供了洞察力.
科学领域:
- 基因组学
- 分子生物学
- 进化生物学
背景情况:
- 由于重复的DNA和大小, 人类的中间体难以测序.
- 了解中心变异,进化和功能至关重要但不完整.
- 人类基因组中突变最快的区域之一.
研究的目的:
- 通过使用先进的长读技术, 完整地测序和组装所有人类的中间体.
- 为了比较两个人类基因组之间的中心变异.
- 调查灵长类动物中中心体的进化动态.
主要方法:
- 长时间阅读第二个人类基因组的测序.
- 与参考人类基因组对中心基因序列的比较分析.
- 从黑猩猩,猩猩和基因组中测序和组装正统的中间体.
- DNA甲基化和CENP-A染色体免疫沉.
主要成果:
- 与独特的基因组区域相比,中间体的单核酸变异至少增加了4.1倍,大小变异高达3倍.
- 45.8%的中心序列由于新的α-卫星高阶重复 (HORs) 无法与标准方法连接.
- 根据DNA甲基化和CENP-A ChIP,26%的中间体呈现出不同的动核位置 (> 500 kb).
- 对灵长类动物进行的比较分析显示,阿尔法卫星HOR的几乎完全转换,具有特定物种的变化.
- 遗传学分析表明新型阿尔法卫星HOR的中心体重组有限,并具有单体起源.
结论:
- 人类中间体在序列,大小和表观遗传组织方面表现出广泛的变化.
- 阿尔法卫星HOR的快速进化和周转推动了灵长类动物的中心体多样化.
- 这些发现为估计中心基DNA放大和突变的速率提供了框架.
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