复原病毒插入有助于人类和黑猩猩大脑的分歧
Patricia Gerdes1, Ofelia Karlsson1, Raquel Garza1
1Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.
bioRxiv : the preprint server for biology
|December 19, 2025
概括
内生逆转录病毒,特别是PTERV1,通过创造特定物种的调节元素,影响了人类和黑猩猩大脑的进化. 一次插入阻止了对大脑发育至关重要的人类基因,突出显示了逆转录病毒大流行.
科学领域:
- 进化生物学是进化的生物学.
- 基因组学就是基因组学.
- 神经科学是一个神经科学.
背景情况:
- 人类和黑猩猩的大脑在尺寸,结构和认知方面显示出显著的差异,尽管保留了编码蛋白质的基因.
- 内源逆转录病毒 (ERVs) 已经集成到灵长类动物的基因组中,引入了具有在进化中潜在作用的特定物种的调节元素.
- 对于原始人大脑进化的ERVs的具体贡献仍然在很大程度上未被探索.
研究的目的:
- 为了研究血统特定的PTERV1复原病毒插入在黑猩猩大脑进化中的作用.
- 分析PTERV1插入在黑猩猩神经发育中的表观基因组影响.
- 了解ERV如何促进人类和黑猩猩大脑之间的功能差异.
主要方法:
- 在黑猩猩神经器官中PTERV1插入的表观遗传学分析.
- 用DNA甲基化分析来识别与PTERV1.1相关的异染色质域.
- CRISPR-Cas9基因编辑以删除在黑猩猩诱导的多能干细胞中特定的PTERV1插入.
- 分析神经发育中的LINC00662表达和功能.
主要成果:
- 黑猩猩特有的PTERV1插入被严重甲基化DNA,形成异染色蛋白域,可以影响基因调节.
- 在黑猩猩的染色体19上插入PTERV1阻断了长非编码RNA LINC00662通过DNA甲基化传播的表达.
- 删除PTERV1插入恢复了LINC00662的表达,这对人类大脑发育,神经元成熟和轴突外长至关重要.
结论:
- 像PTERV1这样的内源性逆转录病毒插入,对人类和黑猩猩大脑的功能分歧做出了重大贡献.
- 对ERV插入的DNA甲基化产生了特定物种的调节景观,影响神经基因表达.
- 复原病毒大流行可能通过ERVs的整合和调节在灵长类大脑物种化中发挥了关键作用.
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