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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)