Overview of circadian rhythms

Abstract

The daily light-dark cycle governs rhythmic changes in the behavior and/or physiology of most species. Studies have found that these changes are governed by a biological clock, which in mammals is located in two brain areas called the suprachiasmatic nuclei. The circadian cycles established by this clock occur throughout nature and have a period of approximately 24 hours. In addition, these circadian cycles can be synchronized to external time signals but also can persist in the absence of such signals. Studies have found that the internal clock consists of an array of genes and the protein products they encode, which regulate various physiological processes throughout the body. Disruptions of the biological rhythms can impair the health and well-being of the organism.

Figure 1

Circadian rhythm responses to light.

Figure 2

Schematic representation of the regulation of genes believed to be involved in the circadian clock. BMAL1, Clock, CK1ɛ, mPer, and mCry all are circadian clock genes identified in mice. (Several variants exist of the mPer and mCry genes.) In the cell’s nucleus, the genetic information encoded in these genes is converted into a carrier molecule called mRNA (black wavy lines), which is transported into the fluid within the cell (i.e., the cytoplasm). There, the mRNA is used to generate the protein products encoded by the circadian clock genes (circles and ovals with colors corresponding to the respective genes). Some of these proteins regulate the activity of certain clock genes by binding to “molecular switches” (i.e., E boxes) located in front of those genes. This is called a feedback cycle. Thus, the BMAL1 and clock proteins promote activation of the Per and mCry genes, whereas Per proteins inhibit activation of those genes. The 24-hour cycling comes about as the BMAL1 and Clock proteins induce increased production of Per and Cry proteins. As Pers and Crys accumulate, they inhibit their own synthesis, and the protein levels decline. CK1ɛ protein also helps to regulate Clock protein levels by destabilizing Per protein. NOTE: BMAL1 = brain and muscle ARNT-like 1; CK1ɛ = caseine kinase 1 epsilon; mPer = mouse period; mCry = mouse cryptochrome.