具有高度分化的序列的调节元件在很长的进化距离上得到保护
Mai H Q Phan1,2, Tobias Zehnder2, Fiona Puntieri2
1Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center for Regenerative Therapies, Berlin, Germany.
Nature genetics
|May 27, 2025
概括
大多数发育基因调节元件 (CREs) 在进化时间内迅速发生变化. 然而,这项研究表明,许多序列分离的CREs通过保持保留的基因组位置来维持功能.
科学领域:
- 基因组学就是基因组学.
- 发展生物学 发展生物学
- 进化生物学 进化生物学
背景情况:
- 发育性基因表达对生物体发育至关重要,并且在物种中高度保存.
- 控制基因表达的Cis-regulatory元素 (CREs) 往往缺乏在进化时间内的序列保存,这对理解功能性保存构成了挑战.
- 仅通过保存的基因组位置,独立于序列,CREs维持功能的程度尚未完全理解.
研究的目的:
- 调查尽管有序列分歧,但在保存的基因组位置中,cis-regulatory元素 (CREs) 的功能保存程度.
- 开发和应用新的计算方法来识别跨物种的位置保存CREs.
- 通过实验验证已识别的间接保存的CREs的功能.
主要方法:
- 在小鼠和的胚胎心脏中对调节元素进行比较基因组学分析.
- 开发和应用基于合成的算法"跨物种点投影"以识别位置保存的CREs.
- 在体内报告员对小鼠胚胎进行测试,以验证保存的增强剂的功能.
主要成果:
- 大多数 cis调节元件 (CREs) 在小鼠和之间几乎没有序列保存.
- "跨物种点预测"算法发现了比传统的基于对齐的方法显著更多的位置保存的CREs ("间接保存的"正义词).
- 间接保存的CREs与序列保存的CREs具有相同的染色质和序列组成相似之处,但表现出更大的转录因子结合点周转率.
- 在体内验证证了间接保存增强剂的调节功能.
结论:
- 通过保留基因组位置,即使有显著的序列分歧,也可以保持 cis 调节元件 (CREs) 的功能性保存.
- 像"物种间点投影"这样的新型计算方法对于发现跨进化距离的隐藏功能性保护至关重要.
- 这项工作扩大了我们对基因组进化和保护发育过程背后的机制的理解.
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