Variation in NAT2 acetylation phenotypes is associated with differences in food-producing subsistence modes and ecoregions in Africa

Abstract

BackgroundDietary changes associated to shifts in subsistence strategies during human evolution may have induced new selective pressures on phenotypes, as currently held for lactase persistence. Similar hypotheses exist for arylamine N-acetyltransferase 2 (NAT2) mediated acetylation capacity, a well-known pharmacogenetic trait with wide inter-individual variation explained by polymorphisms in the NAT2 gene. The environmental causative factor (if any) driving its evolution is as yet unknown, but significant differences in prevalence of acetylation phenotypes are found between hunter-gatherer and food-producing populations, both in sub-Saharan Africa and worldwide, and between agriculturalists and pastoralists in Central Asia. These two subsistence strategies also prevail among sympatric populations of the African Sahel, but knowledge on NAT2 variation among African pastoral nomads was up to now very scarce. Here we addressed the hypothesis of different selective pressures associated to the agriculturalist or pastoralist lifestyles having acted on the evolution of NAT2 by sequencing the gene in 287 individuals from five pastoralist and one agriculturalist Sahelian populations.ResultsWe show that the significant NAT2 genetic structure of African populations is mainly due to frequency differences of three major haplotypes, two of which are categorized as decreased function alleles (NAT2*5B and NAT2*6A), particularly common in populations living in arid environments, and one fast allele (NAT2*12A), more frequently detected in populations living in tropical humid environments. This genetic structure does associate more strongly with a classification of populations according to ecoregions than to subsistence strategies, mainly because most Sahelian and East African populations display little to no genetic differentiation between them, although both regions hold nomadic or semi-nomadic pastoralist and sedentary agriculturalist communities. Furthermore, we found significantly higher predicted proportions of slow acetylators in pastoralists than in agriculturalists, but also among food-producing populations living in the Sahelian and dry savanna zones than in those living in humid environments, irrespective of their mode of subsistence.ConclusionOur results suggest a possible independent influence of both the dietary habits associated with subsistence modes and the chemical environment associated with climatic zones and biomes on the evolution of NAT2 diversity in sub-Saharan African populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-015-0543-6) contains supplementary material, which is available to authorized users.

N-Acetyltransferase-2 (NAT2) phenotype is influenced by genotype-environment interaction in Ethiopians

“…Subsistence mode of a population, which determines the exposure to different substances through dietary habit or a lifestyle, can direct and adjust the metabolism of an individual to a favorable scope and level with time [8, 52]. Diet rapidly and reproducibly alters the human gut microbiome [21] and it is a major determinant of gut microbial composition, which is different between Europe and Africa.…”

Genetic history of the African Sahelian populations

“…A study analysing the genetic structure of human populations living either in the Sahel belt or in surrounding African ecosystems showed that the predicted prevalence of NAT2 slow acetylation is significantly higher among pastoralists than among farmers in those regions, but also among populations living in the Sahel/Savannah belt than among those living in humid tropical and equatorial zones, irrespective of their lifestyle. Two alternative hypotheses have been proposed, both of which invoke selective pressures acting on the evolution of this specific gene (due to the dietary or the chemical environment, respectively).…”

“…This hypothesis holds that a slower acetylation phenotype became advantageous in the new dietary environments of food-producing populations, so that pre-existing alleles conferring a slow enzymatic activity, which were kept at low frequencies through purifying selection, would have become simultaneously positively selected in populations adopting agriculture or animal herding. 95 A study 96 analysing the genetic structure of human populations living either in the Sahel belt or in surrounding African ecosystems showed that the predicted prevalence of NAT2 slow acetylation is significantly higher among pastoralists than among farmers in those regions, but also among populations living in the Sahel/Savannah belt than among those living in humid tropical and equatorial zones, irrespective of their lifestyle. Two alternative hypotheses have been proposed, both of which invoke selective pressures acting on the evolution of this specific gene (due to the dietary or the chemical environment, respectively).…”

Deciphering the fine nucleotide diversity of full HLA class I and class II genes in a well‐documented population from sub‐Saharan Africa

“…In this context, the analysis of the Mandenka population is particularly motivating because it lives in a region where several infectious diseases are highly prevalent. In addition, although sub-Saharan African populations, which represent more than 2000 ethno-linguistic groups, 38 have been extensively studied for different genetic markers [39][40][41][42][43][44] including HLA, 29,[45][46][47][48] to our knowledge their HLA molecular variability has not been analysed so far at its greatest degree of detail, that is, the nucleotide level. In this study, we thus investigated the nucleotide polymorphism of 8 extended HLA genes in a sample of the Mandenka population by using full-gene NGS-MiSeq high-throughput sequencing.…”