NAT2 gene diversity and its evolutionary trajectories in the Americas

BISSO-MACHADO, R; RAMALLO V; PAIXÃO-CÔRTES VR; HUNEMEIER, T.; BORTOLINI, MC

Congreso; 60º CONGRESSO BRASILEIRO DE GENÉTICA; 2014

N-acetyltransferase 2 (NAT2) is responsible for the metabolization of xenobiotics (drugs and exogenous chemicals present in the diet and environment). NAT2 polymorphisms lead to three phenotypes: fast, intermediate and slow acetylators. The present study aimed to expand the knowledge about NAT2 diversity in Native Americans. NAT2 exon 2 was sequenced for 300 individuals from 24 populations: (a) Native Americans: Apalaí, Arara, Gavião, Guarani, Jamamadi, Lengua, Suruí, Wai-wai, Xavante, Zoró, and Totonaco; (b) Andean natives and other communities with high Amerindian ancestry: Uro, Amantani, Anapia, Andoas, Cabanaconde, Chivay, Taquile, Yanque; (c) Other: urban Mexican mestizo; (d) Native Asians: Siberian Eskimo; (d) Africans: Cameroon, Congo, Ivory Coast). These populations were classified according to their mode of subsistence: hunter gatherer or agriculturalist. Excluding the basal/rapid NAT2*4, the most frequent haplotype is NAT2*5B (35.95%) in hunter-gatherers, while NAT2*7B (20.61%) and NAT2*5B (19.08%) are the most prevalent in agriculturalists, all related to the slow phenotype. A new haplotype, possibly related to the slow phenotype, was identified in two Amerindians (1 Suruí and 1 Xavante). Additional data from a ~44kb region surrounding the NAT2 gene in 1,175 individuals from Africa, Asia, Europe and America were also used in some analyses. The Ewens-Wattersons neutrality test was used and a signal for directional selection was observed in Mesoamerican agriculturalists, but not in Andean agriculturalists or Amerindian hunter-gatherers/foragers, suggesting that the NAT2 allele distributions in America can deviate from neutral expectations. It is noteworthy that the majority of the Pre-Columbian Mesoamerican populations had maize as the base of their diet, contrary to the other groups studied here, which had a much more variable diet. These distinct diets and lifestyles could be associated to the NAT2 frequencies in Native Americans