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

Silvia Parolo, Sébastien Lacroix, Jim Kaput, Marie-Pier Scott-Boyer

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. 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. 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. 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.