Humans and Chimpanzees Display Opposite Patterns of Diversity in Arylamine N-Acetyltransferase Genes - Archive ouverte HAL Access content directly
Journal Articles G3 Year : 2019

Humans and Chimpanzees Display Opposite Patterns of Diversity in Arylamine N-Acetyltransferase Genes

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Christelle Vangenot
  • Function : Author
Pascal Gagneux
  • Function : Author
Natasja de Groot
  • Function : Author
Adrian Baumeyer
  • Function : Author
Médéric Mouterde
  • Function : Author
Brigitte Crouau-Roy
  • Function : Author
Pierre Darlu
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  • PersonId : 1103099
Alicia Sanchez-Mazas
  • Function : Author
Audrey Sabbagh
  • Function : Author
Estella Poloni
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Abstract

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’ 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.

Dates and versions

hal-03269113 , version 1 (23-06-2021)

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Christelle Vangenot, Pascal Gagneux, Natasja de Groot, Adrian Baumeyer, Médéric Mouterde, et al.. Humans and Chimpanzees Display Opposite Patterns of Diversity in Arylamine N-Acetyltransferase Genes. G3, 2019, 9 (7), pp.Pages 2199-2224. ⟨10.1534/g3.119.400223⟩. ⟨hal-03269113⟩
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