2023,
Genome Biology.
DOI:
10.1186/s13059-023-03019-3
The relationship between regulatory changes in cis and trans and the evolution of gene expression in humans and chimpanzees
Kenneth A. Barr, Katherine L. Rhodes, Yoav Gilad
Abstract:
Abstract
Background
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.
Results
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.
Conclusions
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.
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2023-09-24 14:05:00
徐炳祥:
#paper doi: 10.1186/s13059-023-03019-3 Genome Biology, 2023, The relationship between regulatory changes in cis and trans and the evolution of gene expression in humans and chimpanzees。对灵长类动物进行比较基因组学研究受限于伦理因素和材料获取的困难而一直进展缓慢。由iPSC细胞诱导获得的胚胎样团（EB）是进行此类研究的好材料。本文作者使用人类和大猩猩的iPSC细胞分别诱导获得了EB，并使用单细胞RNA-seq进行了基因表达的比较分析。结果显示，胚胎样团中已包含大量已知细胞类型。对不同类型的细胞进行人-猩猩的基因差异表达分析鉴定了一系列差异表达基因。与序列保守性和基因功能注释进行比对发现在多个细胞类型中存在差异的基因与更低的序列保守性和人与猩猩的差异有关，而在各细胞类型中表达保守的基因集中于基础生命过程。进一步，作者使用人-猩猩融合细胞构建了EB并借此将表达差异分解为顺式和反式两类，证明了反式差异与两个物种的基因表达调控网络差异有关。作为一项干湿结合的研究，本文仅有3位作者。新产出数据量也不大。是资源/规模有限的研究组通过发挥专长和优化的实验设计在避免堆砌数据的前提下解决重大生物问题的良好范例。