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

Author:

Starr Alexander L.,Gokhman David,Fraser Hunter B.ORCID

Abstract

AbstractMeasuring 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.

Funder

Foundation for the National Institutes of Health

U.S. Department of Defense

Publisher

Springer Science and Business Media LLC

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