Genetics of Circadian Rhythms

Abstract

In mammals, genetic influences of circadian rhythms occur at many levels. A set of core "clock genes" have been identified that form a feedback loop of gene transcription and translation. The core genetic clockwork generates circadian rhythms in cells throughout the body. Polymorphisms in both core clock genes and interacting genes contribute to individual differences in the expression and properties of circadian rhythms. The circadian clock profoundly influences the patterns of gene expression and cellular functions, providing a mechanistic basis for the impact of the genetic circadian system on normal physiological processes as well as the development of diseases.

Keywords: Circadian rhythms; Clock genes; Patterns of gene activity; Polymorphisms.

Figure 1. Multidimensional genetic clockwork.

The core clock of animals has the proteins CLOCK and BMAL1 functioning as positive regulators, binding to E-box regulatory elements and transactivating the transcription of the per and Cry genes, as well as multiple other rhythmically expressed genes. Phosphorylation of PER by CSNK1 can lead to its degradation. PER and CRY proteins form dimers and enter the nucleus to repress the CLOCK:BMAL1 complex. Rhythmic transcription leads to rhythms in key regulator genes and cellular functions that can feedback to alter core clock function. In addition, CLOCK affects histone acetylation, another mechanism by which gene activity can be modulated.