Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients
Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients
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DOI：
10.1038/s41467-019-14269-w
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发表时间：
2020-01-16
影响因子：
16.6
通讯作者：
Creyghton, Menno P.
中科院分区：
文献类型：
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作者：
Castelijns, Bas;Baak, Mirna L.;Creyghton, Menno P.
物种形成与基因表达背后的调控电路的实质性重新连接有关。确定哪些变化是相关的，是人脑出现的基础，还是它对神经疾病的独特易感性，一直是具有挑战性的。在这里，我们注释了跨越大部分灵长类进化的多个灵长类物种大脑中细胞类型分辨率的基因调控元件(GRE)的变化。我们确定了在人类和黑猩猩分离之前在人类中出现的一组独特的调控元件。我们证明这些人类基因的获得在出生后影响少突胶质细胞的功能，并且在自闭症患者的大脑中优先受到影响。这种对人类特有的GRE的偏好也被观察到，这表明这个系统面临着持续的选择压力。我们的数据提供了灵长类进化过程中的调控调整路线图，提供了对大脑出现及其对神经疾病的易感性背后的基因组变化的洞察。
Speciation is associated with substantial rewiring of the regulatory circuitry underlying the expression of genes. Determining which changes are relevant and underlie the emergence of the human brain or its unique susceptibility to neural disease has been challenging. Here we annotate changes to gene regulatory elements (GREs) at cell type resolution in the brains of multiple primate species spanning most of primate evolution. We identify a unique set of regulatory elements that emerged in hominins prior to the separation of humans and chimpanzees. We demonstrate that these hominin gains perferentially affect oligodendrocyte function postnatally and are preferentially affected in the brains of autism patients. This preference is also observed for human-specific GREs suggesting this system is under continued selective pressure. Our data provide a roadmap of regulatory rewiring across primate evolution providing insight into the genomic changes that underlie the emergence of the brain and its susceptibility to neural disease.