保存元素中人类特异性缺失的功能和进化影响
James R Xue1,2, Ava Mackay-Smith3, Kousuke Mouri4
1Broad Institute of MIT and Harvard, Cambridge, MA, USA.
概括
人类特异性删除 (hCONDEL) 影响大脑发育和功能. 这些基因变化揭示了驱动人类独特特征的进化机制,
科学领域:
- 基因组学
- 进化生物学
- 神经科学
背景情况:
- 保存的基因组序列可以在人类中被破坏,从而解释人类独特的特征.
- 了解这些干扰是人类进化的基因基础的关键.
研究的目的:
- 识别和描述人类特异性的保存删除 (hCONDEL).
- 研究hCONDELs对基因调节和人类特征,特别是大脑发育的功能影响.
主要方法:
- 从基因组数据中识别和描述1032个hCONDEL.
- 对遗传学,表观遗传学和转录学数据集进行分析,以丰富大脑功能.
- 在六种细胞类型中进行大规模并行报告测试,以评估hCONDELs的调节活性.
- 将hCONDEL重返其祖先序列以观察基因表达的变化.
主要成果:
- 发现了10,032个hCONDEL,平均为2.56个基对,用于大脑功能.
- 确定了800个具有显著调节作用的hCONDEL,其中有一半具有增强功能.
- 突出显示影响大脑发育基因的hCONDEL,如HDAC5,CPEB4和PPP2CA.
- 证明逆转hCONDEL会改变LOXL2和与髓化和突触功能相关的基因的表达.
结论:
- hCONDEL是影响基因调节的人类特异性遗传变异的重要来源.
- 这些删除在人类大脑发育和功能进化中起作用.
- 已识别的hCONDEL为研究人类进化和相关特征提供了宝贵的资源.
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