NAT2 gene diversity and its evolutionary trajectory in the Americas.
N-acetyltransferase 2 (NAT2) is responsible for metabolizing xenobiotics; NAT2 polymorphisms lead to three phenotypes: rapid, intermediate and slow acetylators. We aimed to investigate NAT2 diversity in Native Americans. NAT2 exon 2 was sequenced for 286 individuals from 21 populations (Native American and American Mestizos). Excluding the basal/rapid haplotype NAT2*4, the most frequent haplotypes are NAT2*5B (35.95%) in hunter-gatherers and NAT2*7B (20.61%) and NAT2*5B (19.08%) in agriculturalists that were related to the slow phenotype. A new haplotype was identified in two Amerindians. Data from the ~44 kb region surrounding NAT2 in 819 individuals from Africa, East-Asia, Europe and America were used in additional analyses. No significant differences in the acetylator NAT2 haplotype and phenotype distributions were found between Native American populations practicing farming and/or herding and those practicing hunting and gathering, probably because of the absence or weakness of selection pressures and presence of demographic and random processes preventing detection of any selection signal.
Laboratório de Evolução Humana e Molecular, Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
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Bisso-Machado
Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Puerto Madryn, Argentina.
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Ramallo
Laboratório de Evolução Humana e Molecular, Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
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Paixão-Côrtes
Molecular Genetics Laboratory, Escuela Nacional de Antropología e Historia, Mexico City, Mexico.
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Acuña-Alonzo
Instituto de Antropología de Córdoba, CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina.
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Demarchi
Facultad de Medicina Humana, Universidad de San Martin de Porres, Lima, Peru.
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Sandoval
Facultad de Medicina Humana, Universidad de San Martin de Porres, Lima, Peru.
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Granara
Laboratório de Evolução Humana e Molecular, Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
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Salzano
Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
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Hünemeier
Laboratório de Evolução Humana e Molecular, Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
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Bortolini
D000107:Acetylation; D000383:Agriculture; D044467:American Indian or Alaska Native / Q000235:genetics*; D000569:Americas; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D004032:Diet / Q000208:ethnology; D019143:Evolution, Molecular; D005247:Feeding Behavior / Q000208:ethnology; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007700:Kinetics; D010641:Phenotype; D011235:Predatory Behavior; D015262:Xenobiotics / Q000378:metabolism
D015262:Xenobiotics; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human