Accounting for cis-regulatory constraint prioritizes genes likely to affect species-specific traits

Genome Biology

Method

Alexander L. Starr¹  Hunter B. Fraser¹  David Gokhman² 

[1] Department of Biology, Stanford University, Stanford, CA, USA;Department of Biology, Stanford University, Stanford, CA, USA;Present Address: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel;

关键词: Hybrid;    Gene expression;    Evolution;    Human;    Chimpanzee;    Primate;    Brain;    Development;   

DOI  :  10.1186/s13059-023-02846-8

 received in 2022-06-23, accepted in 2023-01-04,  发布年份 2023

来源: Springer

【 摘 要 】

Measuring allele-specific expression in interspecies hybrids is a powerful way to detect cis-regulatory changes underlying adaptation. However, it remains difficult to identify genes most likely to explain species-specific traits. Here, we outline a simple strategy that leverages population-scale allele-specific RNA-seq data to identify genes that show constrained cis-regulation within species yet show divergence between species. Applying this strategy to data from human-chimpanzee hybrid cortical organoids, we identify signatures of lineage-specific selection on genes related to saccharide metabolism, neurodegeneration, and primary cilia. We also highlight cis-regulatory divergence in CUX1 and EDNRB that may shape the trajectory of human brain development.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 1

40798_2022_490_Article_IEq63.gif

40798_2022_490_Article_IEq54.gif

40798_2022_490_Article_IEq12.gif

Fig. 58

Fig. 5

12888_2022_4500_Article_IEq2.gif