@article {320057, title = {Humans and Chimpanzees Display Opposite Patterns of Diversity in Arylamine N-Acetyltransferase Genes}, journal = {G3 (Bethesda)}, volume = {9}, number = {7}, year = {2019}, note = {

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}, month = {07/2019}, pages = {2199-2224}, abstract = {

Among the many genes involved in the metabolism of therapeutic drugs, human arylamine\ N-acetyltransferases (NATs) genes have been extensively studied, due to their medical importance both in pharmacogenetics and disease epidemiology. One member of this small gene family,\ NAT2, is established as the locus of the classic human acetylation polymorphism in drug metabolism. Current hypotheses hold that selective processes favoring haplotypes conferring lower\ NAT2\ activity have been operating in modern humans{\textquoteright} recent history as an adaptation to local chemical and dietary environments. To shed new light on such hypotheses, we investigated the genetic diversity of the three members of the\ NAT\ gene family in seven hominid species, including modern humans, Neanderthals and Denisovans. Little polymorphism sharing was found among hominids, yet all species displayed high\ NAT\ diversity, but distributed in an opposite fashion in chimpanzees and bonobos (Pan\ genus) compared to modern humans, with higher diversity in\ Pan\ species at\ NAT1\ and lower at\ NAT2, while the reverse is observed in humans. This pattern was also reflected in the results returned by selective neutrality tests, which suggest, in agreement with the predicted functional impact of mutations detected in non-human primates, stronger directional selection, presumably purifying selection, at\ NAT1\ in modern humans, and at\ NAT2\ in chimpanzees. Overall, the results point to the evolution of divergent functions of these highly homologous genes in the different primate species, possibly related to their specific chemical/dietary environment (exposome) and we hypothesize that this is likely linked to the emergence of controlled fire use in the human lineage.

}, isbn = {2160-1836}, doi = {https://doi.org/10.1534/g3.119.400223}, url = {https://www.g3journal.org/content/9/7/2199}, author = {Vangenot, C and Gagneux, P and de Groot, NG and Baumeyer, A and Mouterde, M and Crouau-Roy, B and Darlu, P and Sanchez-Mazas, A and Sabbagh, A and Poloni, ES} }