User:Bhuggins2/New Sandbox

The Evolution of the Vitamin D Receptor

A functional vitamin D receptor (VDR) can be found in almost all vertebrate animals. Vitamin D acts as a potent steroid hormone to regulate the transcription of over 900 genes via interactions with the VDR. Together with the retinoid X receptor (RXR), the VDR can regulate transcription via activation or repression of various target genes. The different genes that are subject to such transcriptional regulation are marked by distinct vitamin D receptor elements (VDRE), which are generally located in the 5′ upstream regions of a variety of vitamin D target genes. Through transcriptional regulation, vitamin D plays an important role in various biological processes including growth, development, antioxidation, and homeostasis in vital tissues.

Although the VDR is found across vertebrate animals, vitamin D metabolites can be traced to the earliest signs of life. In organisms such as algae and plankton, the cholesterol derivative, 7-dehydrocholesterol, is actively converted to vitamin D3 upon exposure to ultraviolet B (UVB) radiation. This photoconversion has occurred for millions of years and is thought to have originally acted as a form of protective sunscreen from harmful ultraviolet radiation (UV). This would have been necessary as there was little to no protection from UV radiation due to an unestablished ozone layer. However, sterol molecules, such as vitamin D metabolites, have the potential to act as strong nutritional signaling molecules. This is thought to have lead to selective pressure resulting in the evolution of transcription factors which respond to environmental cues and control gene regulation. Through an adaptation process involving major gene duplications, the nuclear receptor (NR) family evolved, including the NR1H and NR1I families.

These receptors are the original families that gave rise to modern receptors that are sensors for cholesterol derivatives, such as oxysterols, bile acids, and vitamin D. Receptors in this family can be found across the tree of life, including in invertebrates like Caenorhabditis elegans (C. elegans), cartilaginous fish such as lamprey, and all other vertebrate organisms.

.... more to come

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