Vitamin D in the Context of Evolution

Abstract

For at least 1.2 billion years, eukaryotes have been able to synthesize sterols and, therefore, can produce vitamin D when exposed to UV-B. Vitamin D endocrinology was established some 550 million years ago in animals, when the high-affinity nuclear receptor VDR (vitamin D receptor), transport proteins and enzymes for vitamin D metabolism evolved. This enabled vitamin D to regulate, via its target genes, physiological process, the first of which were detoxification and energy metabolism. In this way, vitamin D was enabled to modulate the energy-consuming processes of the innate immune system in its fight against microbes. In the evolving adaptive immune system, vitamin D started to act as a negative regulator of growth, which prevents overboarding reactions of T cells in the context of autoimmune diseases. When, some 400 million years ago, species left the ocean and were exposed to gravitation, vitamin D endocrinology took over the additional role as a major regulator of calcium homeostasis, being important for a stable skeleton. Homo sapiens evolved approximately 300,000 years ago in East Africa and had adapted vitamin D endocrinology to the intensive exposure of the equatorial sun. However, when some 75,000 years ago, when anatomically modern humans started to populate all continents, they also reached regions with seasonally low or no UV-B, i.e., and under these conditions vitamin D became a vitamin.

Keywords: calcium homeostasis; energy metabolism; evolution; immune system; migration of Homo sapiens; vitamin D.

Figure 1

Principles of endogenous vitamin D₂ and vitamin D₃ production. In fungi, vitamin D₂ is produced non-enzymatically when the sterol ergosterol is exposed to UV-B radiation. In cholesterol synthesizing animals (as well as in some plants, such as phytoplankton), 7-dehydrocholesterol reacts to vitamin D₃ using the energy of UV-B. Animals express enzymes that convert vitamin D₃ first to 25(OH)D₃ and then to 1,25(OH)₂D₃. In animals (but not in fungi), vitamin D endocrinology developed and 1,25(OH)₂D₃ acts as a hormone binding with high affinity to the nuclear receptor VDR (green, the co-receptor RXR is shown in blue). In the example of cholesterol, the numbering of rings (A-D) and carbons (1-27) is indicated, while only key carbons are marked in the other molecules.

Figure 2

Timeline of evolution. The evolutionary history of the past 4.6 billion years (top), 1 billion years (center) and 70,000 years (bottom) are depicted. Important events discussed in this review are indicated and the time of their approximate occurrence is marked.

Figure 3

Schematic representation of the admixture of the European population. All European populations derived from European hunter–gatherers, Anatolian farmers and Yamnaya pastoralists [84]. A pie chart indicates the typical admixture of the founding populations (center). Melanin is produced in melanosomes under the control of the proteins OCA2, SLC24A5 and SLC45A2 (top).