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

Paper Abstract:

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.

Description of Code:

Contains all code used to analyze data and generate figures for this manuscript (although figures were edited directly in biorender in some instances).  Also contains a zipped file containing annotated scripts and data (from GTEx) that can be used to run the method outlined in the paper "Z_Score_For_Users".  Users can also use the method with different population-scale ASE data from different species.