The relationship between regulatory changes in cis and trans and the evolution of gene expression in humans and chimpanzees.

The relationship between regulatory changes in cis and trans and the evolution of gene expression in humans and chimpanzees.
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DOI:
10.1186/s13059-023-03019-3
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发表时间:
2023-09-11
期刊:
影响因子:
12.3
通讯作者:
--
中科院分区:
生物学1区
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--
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类人猿的比较基因表达研究从根本上受到了跨不同组织采样的挑战。在这里,我们使用了类胚体的单细胞RNA测序来收集来自三个人和三个黑猩猩的70多种细胞类型的转录数据。我们发现了数百个基因,它们的调节在不同的细胞类型中是保守的,以及在一种或几种细胞类型中,其调节可能在定向选择下进化的基因。利用人-黑猩猩融合细胞系的类胚体,我们还推断了由于物种之间顺式和反式元件的变化而导致的物种间调控差异的比例。利用顺式/反式推理和转录因子结合位点的分析,我们鉴定了数十种转录因子,它们的物种间表达差异正在影响人类和黑猩猩在数百个靶基因上的表达差异。在这里,我们提供了迄今为止人类和黑猩猩基因表达比较的最全面的数据集,包括与物种间差异相关的调控机制的目录。网上版载有补充材料,可在10.1186/s13059-023-03019-3查阅。
Comparative gene expression studies in apes are fundamentally limited by the challenges associated with sampling across different tissues. Here, we used single-cell RNA sequencing of embryoid bodies to collect transcriptomic data from over 70 cell types in three humans and three chimpanzees. We find hundreds of genes whose regulation is conserved across cell types, as well as genes whose regulation likely evolves under directional selection in one or a handful of cell types. Using embryoid bodies from a human-chimpanzee fused cell line, we also infer the proportion of inter-species regulatory differences due to changes in cis and trans elements between the species. Using the cis/trans inference and an analysis of transcription factor binding sites, we identify dozens of transcription factors whose inter-species differences in expression are affecting expression differences between humans and chimpanzees in hundreds of target genes. Here, we present the most comprehensive dataset of comparative gene expression from humans and chimpanzees to date, including a catalog of regulatory mechanisms associated with inter-species differences. The online version contains supplementary material available at 10.1186/s13059-023-03019-3.
来自1,092个人基因组的遗传变异的综合图。
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