Abstract
BackgroundOne of the most important dietary shifts underwent by human populations began to occur in the Neolithic, during which new modes of subsistence emerged and new nutrients were introduced in diets. This change might have worked as a selective pressure over the metabolic pathways involved in the breakdown of substances extracted from food. Here we applied a candidate gene approach to investigate whether in populations with different modes of subsistence, diet-related genetic adaptations could be identified in the genes AGXT, PLRP2, MTRR, NAT2 and CYP3A5.ResultsAt CYP3A5, strong signatures of positive selection were detected, though not connected to any dietary variable, but instead to an environmental factor associated with the Tropic of Cancer. Suggestive signals of adaptions that could indeed be connected with differences in dietary habits of populations were only found for PLRP2 and NAT2. Contrarily, the demographic history of human populations seemed enough to explain patterns of diversity at AGXT and MTRR, once both conformed the evolutionary expectations under selective neutrality.ConclusionsAccumulated evidence indicates that CYP3A5 has been under adaptive evolution during the history of human populations. PLRP2 and NAT2 also appear to have been modelled by some selective constrains, although clear support for that did not resist to a genome wide perspective. It is still necessary to clarify which were the biological mechanisms and the environmental factors involved as well as their interactions, to understand the nature and strength of the selective pressures that contributed to shape current patterns of genetic diversity at those loci.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0212-1) contains supplementary material, which is available to authorized users.
Highlights
One of the most important dietary shifts underwent by human populations began to occur in the Neolithic, during which new modes of subsistence emerged and new nutrients were introduced in diets
Other metabolic-related genes have been hypothesized to constitute dietary adaptations, among which are included: AGXT, coding for alanine:glyoxylate aminotransferase, the enzyme responsible for the transamination of Valente et al BMC Genetics (2015) 16:55 glyoxylate into glycine [11,12,13]; PLRP2, coding for pancreatic lipase-related protein 2, involved in galactolipids hydrolysis, [14,15,16,17]; MTRR, encoding for methionine synthase reductase, an enzyme acting in the complex folate pathway [15, 18]; NAT2 coding for N-acetyltransferase 2, a phase-II enzyme involved in the detoxification of a wide number of xenobiotics [15, 19,20,21,22,23]; and CYP3A5, coding for cytochrome P-450 3A5, a member of the CYP3A enzymes that are involved in the oxidative metabolism of many endogenous substrates and xenobiotics, which is implied in sodium homeostasis [24,25,26,27]
The hypothesis was investigated by Caldwell et al [11] who reported on frequency data sustaining the model, a conclusion for which much accounted the observation of the highest frequency of the derived allele in the Sweden Saami, who have a long history of consuming high amounts of animal products [11, 28]
Summary
One of the most important dietary shifts underwent by human populations began to occur in the Neolithic, during which new modes of subsistence emerged and new nutrients were introduced in diets. Genetic variation in AGXT was tentatively linked with meat content in diets, PLRP2 with richness in cereals [15], both MTRR and NAT2 with availability of folate in foods and CYP3A5 with health conditions that are influenced by dietary salt intake [24, 27]. For these 5 genes results so far obtained were either contradictory (e.g. AGXT), or not yet replicated (e.g. MTRR and PLRP2), or not clear enough to ascertain whether they can represent genetic adaptations to any dietary variable. Assuming that current modes of subsistence are still good surrogates of main diets in which populations have traditionally relied, the aim of this study was to gain further insights into the relationship between dietrelated variables in populations and patterns of diversity at variations in above mentioned five genes
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