人类cis调节元件和转录因子结合位点的哺乳动物进化
Gregory Andrews1, Kaili Fan1, Henry E Pratt1
1Program in Bioinformatics and Integrative Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
概括
研究人员为人类的调节元素绘制了进化路径, 关键基因附近的受约束元素突出显示了细胞的基本作用,而灵长类特异性基因则与免疫等环境相互作用有关.
科学领域:
- 基因组学
- 进化生物学
- 生物信息学
背景情况:
- 了解人类基因组的调节环境对于现代生物学来说至关重要.
- 候选 cis 调节元件 (cRE) 和转录因子结合位 (TFBS) 是基因调节的关键.
研究的目的:
- 在哺乳动物基因组中绘制人类cCREs和TFBS的进化轨迹.
- 在进化约束下识别调节元素及其相关的基因功能.
- 调查TFBS的起源和演变,包括从可转移的元素中衍生出来的TFBS.
主要方法:
- 241个哺乳动物基因组的无参考对齐.
- 分析了920万人的cCREs和1560万人的TFBS.
- 限制元素的识别和序列变异的丰富分析.
主要成果:
- 发现439,461个cCREs和2,024,062个TFBS受到进化约束.
- 接近受约束元素的基因参与了基本的细胞过程.
- 靠近灵长类特有的基因与环境相互作用有关,包括嗅觉和免疫力.
- 大约20%的TFBS来自具有复杂进化模式的可转移元素.
- 与复杂特征相关的序列变异在受约束的TFBS中得到了丰富.
结论:
- 进化约束为理解人类调节元素的功能意义提供了一个强大的镜头.
- 这项研究揭示了人类基因组的调节功能和TFBS的进化动态.
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