BackgroundGenetic variation at NAT2 has been long recognized as the cause of differential ability to metabolize a wide variety of drugs of therapeutic use. Here, we explore the pattern of genetic variation in 12 human populations that significantly extend the geographic range and resolution of previous surveys, to test the hypothesis that different dietary regimens and lifestyles may explain inter-population differences in NAT2 variation.Methodology/Principal FindingsThe entire coding region was resequenced in 98 subjects and six polymorphic positions were genotyped in 150 additional subjects. A single previously undescribed variant was found (34T>C; 12Y>H). Several aspects of the data do not fit the expectations of a neutral model, as assessed by coalescent simulations. Tajima's D is positive in all populations, indicating an excess of intermediate alleles. The level of between-population differentiation is low, and is mainly accounted for by the proportion of fast vs. slow acetylators. However, haplotype frequencies significantly differ across groups of populations with different subsistence.Conclusions/SignificanceData on the structure of haplotypes and their frequencies are compatible with a model in which slow-causing variants were present in widely dispersed populations before major shifts to pastoralism and/or agriculture. In this model, slow-causing mutations gained a selective advantage in populations shifting from hunting-gathering to pastoralism/agriculture. We suggest the diminished dietary availability of folates resulting from the nutritional shift, as the possible cause of the fitness increase associated to haplotypes carrying mutations that reduce enzymatic activity.

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Northwest Siberia is geographically remote territory, which has been settled by indigenous human populations probably since the Upper Paleolithic.

Vital capacitySmoking and respiratory diseases the interrelations of community members, the social arrangement of traditional Arctic communities also creates an optimal balance with the environment. Therefore, the human infringements on the Arctic's natural environment in the "new industrial development areas" result not only in eco-catastrophes but also in social reorganization. Today, the nomadic and semi-nomadic groups still maintain a way of life that is close to tradition and is based on reindeer herding,

The results demonstrate that "modernization" and urbanization have a serious stressing influence on the aborigines of North Siberia.