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

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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Jan 19, 2023
Source ID
10.1186/s13059-023-02846-8

Entities

People

  • Alexander L. Starr
  • David Gokhman
  • Hunter Fraser

Organizations

  • Foundation for the National Institutes of Health
  • United States Department of Defense

Tags

Fields of Study

  • Biology

Readers

  • Molecular Genetics
  • Molecular and genetic basis of cancer.
  • Systems Analysis and Design