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The Short Sleeper Gene & Mutation
Image courtesy of Microsoft Clip Art
The "Short Sleeper" gene, known scientifically as DEC2 or BHLHE41, encodes a protein that is part of a family known as basic helix-loop-helix proteins. Dec2 and the other proteins in this family are transcription factors, meaning that they bind directly to DNA and regulate gene expression by controlling the transcription of DNA into RNA (M.E. Massari & C. Murre, 2000). Specifically, Dec2 is a repressive transcription factor, meaning that it reduces the transcription of certain genes when it binds to DNA. In addition to acting as a transcription factor for a variety of genes, it has also been identified as a component of circadian clocks (S. Honma et al., 2002)
Orthologs of DEC2, or similar genes, have been identified in many vertebrates, including other primates, non-primate mammals, birds, reptiles, amphibians, and fish. In humans, DEC2 is located on the short arm of chromosome 12:
Figure 1. Position of DEC2. The position of DEC2 is denoted by the red line on the short arm of chromosome 12.
Image courtesy of the Genome Browser
DEC2 is expressed at very high levels in the brain and thyroid relative to other tissue types (Su et al., 2004):
Figure 2. Expression of DEC2 in human tissues. DEC2 expression is highest in the brain (green) and thyroid (aqua).
Image modified from the BioGPS Gene Atlas
For additional information on DEC2, please visit the National Center for Biotechnology Information's page on it here.
The "short sleeper" mutation described in both the scientific and public media articles is a single nucleotide polymorphism (SNP), meaning that only one nucleotide base is changed, in this case from a cytosine to a guanine (He et al., 2009). As a result of this mutation, the amino acid argenine is substituted for the amino acid proline at the 385th amino acid position in the protein (He et al., 2009). This mutation is notated P385R. The proline in the 385th amino acid position is highly conserved throughout mammalian genomes, which suggests that the proline in this position is important to the function of the protein and that natural selection has selected against deviations from proline at this position (He et al., 2009).
References
He, Y., Jones, C. R., Fujiki, N., Xu, Y., Guo, B., Holder, J. L., Rossner, M. J., Nishino, S., and Fu, Y. 2009. The Transcriptional Repressor DEC2 Regulates Sleep Length in Mammals. Science. 325: 866-870.
Honma, S., Kawamoto, T., Takagi, Y., Fujimoto, K., Sato, F., Noshiro, M., Kato, Y., and Honma, K. 2002. Dec1 and Dec2 are regulators of the mammalian molecular clock. Nature. 419: 841-844.
Massari, M. E. & Murre, C. 2000. Helix-loop-helix proteins: Regulators of transcription in eucaryotic organisms. Mollecular and Cellular Biology. 20: 429-440.
Su, A. I., Wiltshire, T., Batalov, S., Lapp, H., Ching, K. A., Block, D., Zhang, J., Soden, R., Hayakawa, M., Kreiman, G., Cooke, M. P., Walker, J. R., and Hogenesch, J. B. 2004. A gene atlas of the mouse and human protein-encoding transcriptomes. Proceedings of the National Academy of Sciences. 101: 6062-6067.
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