Global impact of micronutrients in modern human evolution

Micronutrients are essential components of the human diet, but dietary levels above or below their narrow, recommended range are harmful. Deficiencies increase the risk of stunted growth and metabolic, infectious, and respiratory disorders, and have likely been pervasive in human history, as local soils poor in micronutrients are widespread. Deficiencies are also common today, affecting approximately 2 billion people. Limited evidence exists for selenium, zinc, iodine, and iron deficiencies driving local adaptation in a few human populations, but the broader potential role of micronutrients in shaping modern human evolution remains unclear. Here, we investigate signatures of positive selection in 276 genes associated with 13 micronutrients and evaluate whether human adaptation across global populations has been driven by micronutrients. We identify known and previously undescribed instances of rapid local adaptation in micronutrient-associated genes in particular populations, including previously undescribed individual signatures of adaptation across most of the world. Further, we identify signatures of oligogenic-positive selection in multiple populations at different geographic and temporal scales, with some recapitulating known associations of geology and micronutrient deficiencies. We conclude that micronutrient deficiencies have likely shaped worldwide human evolution more directly than previously appreciated and, given the ongoing depletion of soil quality from over-farming and climate change, caution that some populations may be at higher risk of suffering from micronutrient-driven disorders going forward.