The modern human aryl hydrocarbon receptor is more active when ancestralized by genome editing

Abstract

All present-day humans carry an amino acid substitution in the aryl hydrocarbon receptor (AHR), a transcription factor that induces the expression of cytochrome P450 genes. When the AHR gene is modified to encode the ancestral form of the protein seen in Neandertals and other non-modern human primates, the expression of AHR target genes is increased both in the absence of exogenous ligands and when ligands are added to the cells. Thus, compared to the ancestral variant present in archaic hominins and primates, the AHR in modern humans has a reduced ability to induce the expression of its target genes. This may represent an adaptation to exposure to polycyclic aromatic hydrocarbons in modern humans. Keywords: genetics, evolution, anthropology