Vitamin D: calcium and bone homeostasis during evolution.

Area of Science:

• Evolutionary biology
• Endocrinology
• Biochemistry

Background:

• Vitamin D, initially an inactive photochemical product, evolved a complex endocrine system in vertebrates.
• This system includes the vitamin D receptor (VDR), metabolizing CYP450 enzymes, and transport proteins.
• Its origins may lie in a gene duplication related to xenobiotic detoxification pathways in early vertebrates.

Purpose of the Study:

• To trace the evolutionary journey of the vitamin D endocrine system.
• To elucidate the role of vitamin D in calcium and bone homeostasis across vertebrate evolution.
• To understand vitamin D's contribution to skeletal adaptation in terrestrial environments.

Main Methods:

• Comparative analysis of vitamin D metabolism and VDR across vertebrate lineages.
• Review of existing literature on vitamin D's physiological roles.
• Examination of the genetic and molecular mechanisms underlying vitamin D action.

Main Results:

• The complete vitamin D endocrine system is unique to vertebrates, originating possibly from a PRX/VDR ancestor gene.
• Vitamin D became crucial for calcium and bone homeostasis, preventing rickets in terrestrial vertebrates.
• 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) plays a key role in bone resorption via osteoclasts and mineralization through SIBLING proteins.

Conclusions:

• The vitamin D endocrine system evolved from a simple molecule to a critical regulator of skeletal health.
• Vitamin D is indispensable for maintaining calcium and bone homeostasis in terrestrial animals.
• The system's development was essential for vertebrates adapting to terrestrial life with higher gravity and lower calcium availability.