Abstract
Zinc transporters play important roles in all eukaryotes by maintaining the rational zinc concentration in cells. However, the diversity of zinc transporter genes (ZTGs) remains poorly studied. Here, we investigated the genetic diversity of 24 human ZTGs based on the 1000 Genomes data. Some ZTGs show small population differences, such as SLC30A6 with a weighted-average FST (WA-FST = 0.015), while other ZTGs exhibit considerably large population differences, such as SLC30A9 (WA-FST = 0.284). Overall, ZTGs harbor many more highly population-differentiated variants compared with random genes. Intriguingly, we found that SLC30A9 was underlying natural selection in both East Asians (EAS) and Africans (AFR) but in different directions. Notably, a non-synonymous variant (rs1047626) in SLC30A9 is almost fixed with 96.4% A in EAS and 92% G in AFR, respectively. Consequently, there are two different functional haplotypes exhibiting dominant abundance in AFR and EAS, respectively. Furthermore, a strong correlation was observed between the haplotype frequencies of SLC30A9 and distributions of zinc contents in soils or crops. We speculate that the genetic differentiation of ZTGs could directly contribute to population heterogeneity in zinc transporting capabilities and local adaptations of human populations in regard to the local zinc state or diets, which have both evolutionary and medical implications.
Highlights
Zinc transporters play important roles in all eukaryotes by maintaining the rational zinc concentration in cells
We first performed an analysis of molecular variance (AMOVA) to examine whether genetic variance among four continental regions is significantly different from populations within each region (Table S1 and Figure S1)
Our analysis showed that SLC30A9 and SLC30A3 had a greater proportion of variance among continental groups than within group, indicating that the two genes were genetically differentiated among continental populations
Summary
Zinc transporters play important roles in all eukaryotes by maintaining the rational zinc concentration in cells. SLC30A8 encodes a zinc transporter which is expressed solely in secretory vesicles of b-cells and the overexpression of SLC30A8 in insulinoma cells increases glucose-simulated insulin secretion[17] Another example is that SLC39A8 was observed to have relationship with body mass index[18]. Due to the uneven global distribution of absorbable zinc in soils, crops and different diet habits, some ZTGs with adaptable variations in different populations might be underlying natural selection as their transporting capability changed, maintaining the balance of intercellular or serous zinc in the human body. We showed that ZTGs harbor many more highly population-differentiated variants compared with random genes and discussed the potential underlying forces shaping the genetic diversity of ZTGs. Further, we reported that SLC30A9 was underlying natural selection in both East Asians (EAS) and Africans (AFR) but in different directions. Our results may subsequently increase our understanding of the evolutionary forces that affect ZTGs, as well as augmenting our knowledge of gene function on zinc homeostasis in different populations and the mechanisms of zinc-related diseases
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