%0 Journal Article
%A Helmbrecht, Nelly
%A Lackner, Martin
%A Maricic, Tomislav
%A Pääbo, Svante
%+ Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
The Leipzig School of Human Origins (IMPRS), Max Planck Institute for Evolutionary Anthropology, Max Planck Society
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
The Leipzig School of Human Origins (IMPRS), Max Planck Institute for Evolutionary Anthropology, Max Planck Society
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
%T The modern human aryl hydrocarbon receptor is more active when ancestralized by genome editing : 
%G eng
%U https://hdl.handle.net/21.11116/0000-000F-47ED-7
%R 10.1073/pnas.2402159121
%7 2024-05-13
%D 2024
%8 13.05.2024
%* Review method: peer-reviewed
%X The aryl hydrocarbon receptor (AHR) is a transcription factor that has many functions in mammals. Its best known function is that it binds aromatic hydrocarbons and induces the expression of cytochrome P450 genes, which encode enzymes that metabolize aro-matic hydrocarbons and other substrates. All present- day humans carry an amino acid substitution at position 381 in the AHR that occurred after the divergence of modern humans  from  Neandertals  and  Denisovans.  Previous  studies  that  have  expressed  the  ancestral and modern versions of AHR from expression vectors have yielded conflicting results with regard to their activities. Here, we use genome editing to modify the endog-enous AHR gene so that it encodes to the ancestral, Neandertal- like AHR protein in human cells. In the absence of exogenous ligands, the expression of AHR target genes is higher in cells expressing the ancestral AHR than in cells expressing the modern AHR, and similar to the expression in chimpanzee cells. Furthermore, the modern human AHR needs higher doses of three ligands than the ancestral AHR to induce the expression of target genes. Thus, the ability of AHR to induce the expression of many of its target genes is reduced in modern humans.
%K genetics; evolution; anthropology
%J Proceedings of the National Academy of Sciences
%O PNAS
%V 121
%N 22
%] e2402159121
%I National Academy of Sciences
%C Washington, D.C.
%@ 0027-8424