Evolution of the vertebrate pineal gland: the AANAT hypothesis

Chronobiol Int. 2006;23(1-2):5-20. doi: 10.1080/07420520500545839.


The defining feature of the pineal gland is the capacity to function as a melatonin factory that operates on a approximately 24 h schedule, reflecting the unique synthetic capacities of the pinealocyte. Melatonin synthesis is typically elevated at night and serves to provide the organism with a signal of nighttime. Melatonin levels can be viewed as hands of the clock. Issues relating to the evolutionary events leading up to the immergence of this system have not received significant attention. When did melatonin synthesis appear in the evolutionary line leading to vertebrates? When did a distinct pineal gland first appear? What were the forces driving this evolutionary trend? As more knowledge has grown about the pinealocyte and the relationship it has to retinal photoreceptors, it has become possible to generate a plausible hypothesis to explain how the pineal gland and the melatonin rhythm evolved. At the heart of the hypothesis is the melatonin rhythm enzyme arylalkylamine N-acetyltransferase (AANAT). The advances supporting the hypothesis will be reviewed here and expanded beyond the original foundation; the hypothesis and its implications will be addressed.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Arylalkylamine N-Acetyltransferase / physiology*
  • Biological Evolution
  • Circadian Rhythm
  • Melatonin / metabolism
  • Models, Biological
  • Photoreceptor Cells, Vertebrate
  • Retina / embryology
  • Time Factors


  • AANAT protein, human
  • Arylalkylamine N-Acetyltransferase
  • Melatonin