Ancestors’ dietary patterns and environments could drive positive selection in genes involved in micronutrient metabolism—the case of cofactor transporters

Genes & Nutrition, Oct 2017

Background During evolution, humans colonized different ecological niches and adopted a variety of subsistence strategies that gave rise to diverse selective pressures acting across the genome. Environmentally induced selection of vitamin, mineral, or other cofactor transporters could influence micronutrient-requiring molecular reactions and contribute to inter-individual variability in response to foods and nutritional interventions. Methods A comprehensive list of genes coding for transporters of cofactors or their precursors was built using data mining procedures from the HGDP dataset and then explored to detect evidence of positive genetic selection. This dataset was chosen since it comprises several genetically diverse worldwide populations whom ancestries have evolved in different environments and thus lived following various nutritional habits and lifestyles. Results We identified 312 cofactor transporter (CT) genes involved in between-cell or sub-cellular compartment distribution of 28 cofactors derived from dietary intake. Twenty-four SNPs distributed across 14 CT genes separated populations into continental and intra-continental groups such as African hunter-gatherers and farmers, and between Native American sub-populations. Notably, four SNPs were located in SLC24A3 with one being a known eQTL of the NCKX3 protein. Conclusions These findings could support the importance of considering individual’s genetic makeup along with their metabolic profile when tailoring personalized dietary interventions for optimizing health.

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Ancestors’ dietary patterns and environments could drive positive selection in genes involved in micronutrient metabolism—the case of cofactor transporters

Parolo et al. Genes & Nutrition Ancestors' dietary patterns and environments could drive positive selection in genes involved in micronutrient metabolism-the case of cofactor transporters Silvia Parolo 0 1 Sébastien Lacroix 0 1 Jim Kaput Marie-Pier Scott-Boyer 1 0 Equal contributors 1 The Microsoft Research, University of Trento Centre for Computational Systems Biology (COSBI) , piazza Manifattura 1, 38068 Rovereto, TN , Italy Background: During evolution, humans colonized different ecological niches and adopted a variety of subsistence strategies that gave rise to diverse selective pressures acting across the genome. Environmentally induced selection of vitamin, mineral, or other cofactor transporters could influence micronutrient-requiring molecular reactions and contribute to inter-individual variability in response to foods and nutritional interventions. Methods: A comprehensive list of genes coding for transporters of cofactors or their precursors was built using data mining procedures from the HGDP dataset and then explored to detect evidence of positive genetic selection. This dataset was chosen since it comprises several genetically diverse worldwide populations whom ancestries have evolved in different environments and thus lived following various nutritional habits and lifestyles. Results: We identified 312 cofactor transporter (CT) genes involved in between-cell or sub-cellular compartment distribution of 28 cofactors derived from dietary intake. Twenty-four SNPs distributed across 14 CT genes separated populations into continental and intra-continental groups such as African hunter-gatherers and farmers, and between Native American sub-populations. Notably, four SNPs were located in SLC24A3 with one being a known eQTL of the NCKX3 protein. Conclusions: These findings could support the importance of considering individual's genetic makeup along with their metabolic profile when tailoring personalized dietary interventions for optimizing health. Positive selection; Cofactor transport; Inter-individual variability; Ancestry; Dietary habits; Biological response Background Diet and food availability shaped genetic variation in humans and left distinct adaptation signals among geographically and culturally diverse populations [ 1–3 ]. Lactase persistence in adults is the prime example of food-based positive selection. Cattle domestication after the Neolithic transition provided access to dairy products and the advantages of an additional source of calories, calcium, protein, and other nutrients [ 4 ]. The ability to utilize this nutrient dense food resulted in a strong positive selective pressure on a variant of the lactase-phlorizin hydrolase gene (LCT) responsible for lactose metabolism in the small intestine [ 5, 6 ]. Other genetic changes can also be selected by food availability. For example, the number of copies of the salivary amylase gene may reflect adaptation to starch-rich diets and with consequences for modern health as amylase copy number variations may be negatively associated with body mass index [ 7–9 ]. Positive adaptation signals have also been described for FADS2, which codes for an enzyme involved in long-chain polyunsaturated fatty acid synthesis. A variant of FADS2 was associated with higher mRNA expression in vegan individuals [10] which have diets typically low in long chain unsaturated fatty acids. Positive selection has also been demonstrated for genes coding for transporters of zinc, an important cofactor of several enzymes and DNA-binding proteins [ 11, 12 ]. The objective of this study was to identify variants showing signs of positive selection in genes coding for cofactor transporters (hereafter referred to as CT and listed in Additional file 1: Table S1). We posit that adaptation to different ecological niches may also select for other genes involved in nutrient transport and metabolism, especially those that affect multiple cellular and biochemical processes such as cofactors or their micronutrient precursors. Cofactor transporter genes may be more susceptible to being influenced by different environments and nutritional habits because of their importance in nutrient absorption and subsequent tissue distribution. To fulfill this objective, genetic differentiation of CTassociated variants were analyzed using data from the Human Genome Diversity Project (HGDP), a dataset chosen because it includes multiple world populations representative of a variety of environments and ancestral nutritional habits [ 1, 13, 14 ]. Using an approached based on principal component analysis (PCA) [ 15–17 ], 24 variants in 14 CT genes with signals of positive selection that could contribute to various disease risks and response to nutritional intervention observed between individuals with different genetic makeup were identified. Results Identification of proteins involved in cofactor transport Public databases (i.e., NCBI PubMed, UniProt, and OMIM databases) were sear (...truncated)


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Silvia Parolo, Sébastien Lacroix, Jim Kaput, Marie-Pier Scott-Boyer. Ancestors’ dietary patterns and environments could drive positive selection in genes involved in micronutrient metabolism—the case of cofactor transporters, Genes & Nutrition, 2017, pp. 28, Volume 12, Issue 1, DOI: 10.1186/s12263-017-0579-x