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.
Highlights
Dietary changes associated to shifts in subsistence strategies during human evolution may have induced new selective pressures on phenotypes, as currently held for lactase persistence
We further showed that this structure is attributable to the genetic differentiation of hunter-gatherer populations but is found among African food-producing communities, as attested by the significant ΦST value of 2.6 % for the FPLS dataset of 13 populations. This significant genetic structure is mainly due to the variation in frequencies of three major haplotypes, two of which are categorized as decreased function alleles (NAT2*5B and N-acetyltransferase 2 (NAT2)*6A), which are frequent in populations living in the dry savanna biome, and one fast allele (NAT2*12A), more frequently detected outside this region than within it
The genetic structure of NAT2 in Africa does not strongly associate with subsistence strategy either, mainly because most Sahelian and East African populations display little to no genetic differentiation between them (Additional file 9: Figure S6), both regions are populated by nomadic or semi-nomadic pastoralist and sedentary agriculturalist communities
Summary
Dietary changes associated to shifts in subsistence strategies during human evolution may have induced new selective pressures on phenotypes, as currently held for lactase persistence. 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 prevail among sympatric populations of the African Sahel, but knowledge on NAT2 variation among African pastoral nomads was up to now very scarce. Subsistence strategies are broadly classified in two opposite categories, i.e., foragers (or hunter-gatherers), relying on the collection of nutriments naturally occurring in the wild, and food-producers whose appearance in the prehistoric record is generally associated with the emergence of the Neolithic [10,11,12] Among the latter, two major modes of production are distinguished, namely agriculture based on the cultivation of domesticated plants, and pastoralism based on the herding of domesticated animals. These two modes of subsistence imply differential usage of space, in that most agricultural societies developed sedentarism whereas communities relying on animal husbandry developed nomadism or transhumance to exploit seasonal variations in the location of pasture areas
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