Ancestralization of the modern human aryl hydrocarbon receptor by genome editing

The aryl hydrocarbon receptor (AHR) is a transcription factor that upon binding ligands induces the expression of cytochrome P450 genes, which encode enzymes that metabolize aromatic hydrocarbons. The AHR carries an amino acid substitution at position 381 in all present-day humans that occurred after the divergence of modern humans from Neandertals and Denisovans. Here, we use genome editing to revert position 381 back to the ancestral state in human cells. Cells were treated with ligands for 4 h followed by RNA extraction and RNA-Seq. Overall design: Comparative gene expression profiling analysis of RNA-seq data for H9 hESC with ancestralized AHR and modern human wild type controls. Cells treated with 50 nM benzo(a)pyrene, 100 nM kynurenic acid, 10 nM indirubin or 5 µM CH-223191 for 4 h. 6 replicates per genotype and treatment.