Adaptation and co-adaptation of skin pigmentation and vitamin D genes in native Americans.

We carried out an exhaustive review regarding human skin color variation and how much it may be related to vitamin D metabolism and other photosensitive molecules. We discuss evolutionary contexts that modulate this variability and hypotheses postulated to explain them; for example, a small amount of melanin in the skin facilitates vitamin D production, making it advantageous to have fair skin in an environment with little radiation incidence. In contrast, more melanin protects folate from degradation in an environment with a high incidence of radiation. Some Native American populations have a skin color at odds with what would be expected for the amount of radiation in the environment in which they live, a finding challenging the so-called "vitamin D-folate hypothesis." Since food is also a source of vitamin D, dietary habits should also be considered. Here we argue that a gene network approach provides tools to explain this phenomenon since it indicates potential alleles co-evolving in a compensatory way. We identified alleles of the vitamin D metabolism and pigmentation pathways segregated together, but in different proportions, in agriculturalists and hunter-gatherers. Finally, we highlight how an evolutionary approach can be useful to understand current topics of medical interest.