Soil to genes: How human genetics adapt to micronutrient deficiencies and excess

A recent study spotlights how micronutrients have imperceptibly driven human evolution, presenting evidence of positive selection among micronutrient-associated gene sets in tested populations. Nutrition Insight speaks with the lead researcher to explore the findings’ implications and how it could propel future studies.

The publication in The American Journal of Human Genetics notes that declining global soil micronutrients are rapidly changing due to climate change, rising CO2 levels, and over-farming. Plus, global migration exposes populations to micronutrient deficiencies or excess without having the genetic adaptations to regulate these levels.

“Additional work, including individuals of genetic ancestry groups not represented by populations used here, is required to address this accelerating issue and health connotations in contemporary populations,” the study underscores.

Micronutrients, including trace minerals and vitamins, are essential to human diets and needed in little quantities, says Jasmin Rees, Ph.D., University College London, UK, who is now a postdoctoral researcher at the University of Pennsylvania, US.

“Micronutrient deficiencies can be super harmful, leading to stunted growth and increased risk of infectious, metabolic, or respiratory diseases. In this sense, any decreases in soil quantity — at least those that result in significant decreases in micronutrient quantity in the diet — should be a concern for human health.”

She explains that in her study, her team reveals how micronutrient availability has likely driven genetic adaptations across populations and environments and, therefore, human genetic variation. 

“This may have resulted in average differences in metabolism, uptake, or regulation of micronutrients at the population level. This means that some populations may be at increased risk of micronutrient deficiency or toxicity if micronutrient levels in the diet were to significantly change — caused by changing soil quality or otherwise.” 

“This may cause or exacerbate health disparities across populations, especially if adequate prevention/intervention of micronutrient deficiency/toxicity is not available across populations.”

Micronutrient-associated adaptations

According to the study, 15 micronutrient-associated genes showed changes that were consistent with positive selection, contributing to previous cases of human adaptation to diet.

The researchers cannot confirm the exact impacts of positive selection on micronutrient uptake, regulation, or metabolism.“We show that many dietary micronutrients have likely driven genetic adaptation across diverse populations, which we speculate has led to differences in metabolism, uptake, or regulation of micronutrients at the population level,” says Rees. 

“This means that different populations may be more susceptible to micronutrient deficiency or toxicity under changing levels of micronutrients in the diet. In other words, populations may have adapted to certain ancestral levels of micronutrients in the diet, but as micronutrient quantities in the diet change, they may now be more likely to suffer micronutrient deficiency or toxicity.”

Researchers identified variations in FXYD2 and MECOM, identified in Central-South Asian populations (Uygur and Brahui, respectively), with soils in this region having high magnesium levels. 

These genes are also linked to hypomagnesemia, a condition caused by a lack of this electrolyte. They speculate that the populations adapted to regulate magnesium intake.

The study also points to an area of selenium-deficient soil spread across China, causing dietary deficiency in local populations. In the most deprived areas, cardiomyopathy Keshan disease and the bone disease Kashin-Beck are at an endemic level. 

Connected to this, the researchers say many East Asian populations show oligogenic adaptation in multiple selenium-associated genes.

Other genes identified include the calcium-associated gene ATP2B2 and the iron-associated genes FTMT and HIF1A. These may have helped humans adapt to dietary changes during the Neolithic transition or colonization of Eurasian environments.

The researchers note strong and widespread adaptations to zinc in seven genes, including SLC30A9 and SLC39A4. Positive selection signatures were seen in at least 10 populations. Soils deficient in iron and zinc are especially found in the Middle East, especially in Iran — where there is a history of zinc-deficiency disorders.

“Among the 13 minerals analyzed, some stood out. In Central America, the Maya who live in regions with iodine-poor soils show strong evidence of genetic changes in genes indicated in iodine regulation or metabolism, which could reflect adaptation to low levels of iodine in the diet,” shares Rees. 

Future studies showing populations having different risks of micronutrient toxicity or deficiency could inform health initiatives.“Similarly, we found that the Mbuti population of Central Africa, another population noted for their short stature and living in environments with iodine-poor soils, also bears signs of genetic adaptation in some of the same iodine-dependent thyroid receptors.” 

In the same region, Rees says another short-statured population was previously recorded to have lower goiter rates than their taller neighbors. Based on this, she speculates that a shorter size might show evolutionary adaptation to low iodine risks.

Call for further research

The researchers cannot confirm the exact impacts of positive selection on micronutrient uptake, regulation, or metabolism without functional analysis of the specific genes or further studies. This is why it remains a hypothesis, adds Rees.

“Additionally, studies integrating large biobank data or public health data would help evaluate if there are indeed differential risks of micronutrient deficiency and toxicity across diverse populations, perhaps driven by past genetic adaptation.” 

“We hope that further studies will directly evaluate the health impacts of the proposed instances of positive selection in response to micronutrient-associated selective pressures,” she underlines.

Rees expects that future studies that demonstrate populations have differential risks to micronutrient toxicity or deficiency would help inform public and global health initiatives.

“Human populations may, on average, differ in their micronutrient metabolism, uptake, or regulation, and those with the strongest evidence of micronutrient-associated adaptation should be prioritized in future genomic medicine studies,” the paper concludes.