As a busy student or businessperson, you might have dreamed of being a short-sleeper, especially during exam season or days with important project. In fact, natural short-sleepers with special genes actually exist in the world. Mutation in DEC2 gene makes this possible.
Image Credit: National Human Genome Research Institute
Genes
Gene is “the basic physical and functional unit of heredity,” and its multiple versions are called alleles. As genes are transcripted and replicated, having some errors during the process is natural. These big and small errors result in genetic mutations. Genetic mutations split into two categories: chromosomal and point mutations. In the chromosomal mutation, the whole segment of chromosome is altered; its types are deletion, duplication, inversion, translocation, and nondisjunction. Point mutation has an alteration in base pair; its types are substitution, insertion, and deletion.
Image Credit: Encyclopedia Britannica
Point Mutation
Since DEC2 mutation is an example of point mutation, let’s go deeper with this category. When gene codes for amino acids, each sequence of three nucleotides, known as codon, codes for one amino acid. Production of a chain of amino acids ends when termination codon (UAG, UAA, UGA) is reached. First, substitution is one nucleotide replacing the other. According to the nucleotide and the position of substitution, the amino acid could be premature (nonsense mutation), different (missense mutation) or the same (silent mutation). Second, insertion is where a new nucleotide inserted into the gene, causing following nucleotides to shift backward (frameshift mutation), which eventually leads to nonsense mutation, or coding for different amino acids (missense downstream). Lastly, deletion is a type of mutation in which a nucleotide is deleted. This could cause frameshift mutation and missense downstream or a missing amino acid.
Image Credit: Expii
Sleep and Hormones
Adequate amount of sleep is essential for proper functioning of brain and body. Suprachiasmatic Nucleus (SCN), located in the anterior hypothalamus, plays a major role in circadian rhythm. When retinal photoreceptor proteins detect light, SCN triggers pineal gland to increase or decrease production of melatonin, a hormone that causes sleepiness. In dark, melatonin level increases, and thus people feel drowsy or easily fall asleep. On the other hand, melatonin level falls with greater exposure to light. Melatonin is not the only hormone linked to sleep cycle; hormone orexin, in contrast to melatonin, causes wakefulness. As orexin level decreases, sleepiness rises. According to a 2018 study by Sharma R. et al, melatonin inhibits orexin level, meaning that their interaction regulates the sleep cycle.
Image Credit: ResearchGate
DEC2
Gene repressor is a binding protein that inhibits transcription of certain genes and suppresses production of mRNA necessary for protein synthesis. There is a repressor linked to circadian rhythm named DEC2 that inhibits production of hormone orexin. In other words, DEC2 regulates sleepiness and wakefulness through altering orexin level. What if the DEC2 gene is mutated? Change in amino acid sequence affects overall shape of protein and its function as well. The substitution mutation from C to G in DEC2 gene sequence causes change in DEC2 by placing an amino acid arginine instead of proline. Consequently, DEC2 becomes a weaker repressor in its mutant form, allowing increased production of orexin. People with DEC2 mutation feel completely rested with about 4-6 hours of sleep while others need more than 8 hours.
DEC2 mutation was first found in 2005 by geneticist Ying-hui Fu and her colleagues; a woman slept 6.25 hours on average and her daughter did about the same while other members of her family had 8 hours of sleep daily. After this finding, the team genetically engineered mice and flies to have mutant DEC2. The result was parallel to the finding: both mutant mice and mutant flies slept one or two hours less than normal ones.
Image Credit: Semantic Scholar
Conclusion
DEC2 mutation is highly rare as less than 0.5% of the population have one. However, there may be more cases since people may not recognize their sleeplessness and genetic test for DEC2 mutant is unavailable. Though having DEC2 mutation seem advantageous, its real value depends on how wisely the person spend extra free time. If you had this “lucky” gene, what would you do in your additional 2-3 hours?
References:
- Nature News, Nature Publishing Group, www.nature.com/scitable/topicpage/genetic-mutation-441/.
- Benarroch, Eduardo E. “Suprachiasmatic Nucleus and Melatonin.” Neurology, Wolters Kluwer Health, Inc. on Behalf of the American Academy of Neurology, 19 Aug. 2008, n.neurology.org/content/71/8/594.
- Dong, Qing, et al. “Familial Natural Short Sleep Mutations Reduce Alzheimer Pathology in Mice.” IScience, Elsevier, 15 Mar. 2022, www.sciencedirect.com/science/article/pii/S2589004222002346.
- “Early Risers Are Mutants.” Science, www.science.org/content/article/early-risers-are-mutants#.Y2ZlivYX0u0.mailto.
- He, Ying, et al. “The Transcriptional Repressor DEC2 Regulates Sleep Length in Mammals.” Science (New York, N.Y.), U.S. National Library of Medicine, 14 Aug. 2009, www.ncbi.nlm.nih.gov/pmc/articles/PMC2884988/.
- Hirano, Arisa, et al. “DEC2 Modulates Orexin Expression and Regulates Sleep.”
- Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 27 Mar. 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC5879715/.
- MM;, Sharma R;Sahota P;Thakkar. “Melatonin Promotes Sleep in Mice by Inhibiting Orexin Neurons in the Perifornical Lateral Hypothalamus.” Journal of Pineal Research, U.S. National Library of Medicine, pubmed.ncbi.nlm.nih.gov/29654707/.
- “Orexins.” Sleep Foundation, 29 Apr. 2022, www.sleepfoundation.org/sleep-aids/orexins.
- Ratan-NM. “The DEC2 Gene and Sleep.” News, 22 July 2019, www.news-medical.net/health/The-DEC2-Gene-and-Sleep.aspx.
- “Repressor.” Genome.gov, www.genome.gov/genetics-glossary/Repressor.
- “This Genetic Mutation Makes People Feel Rested on Just 6 Hours of Sleep.” Science, www.science.org/content/article/genetic-mutation-makes-people-feel-rested-just-6-hours-sleep.
- “What Is a Gene?: MedlinePlus Genetics.” MedlinePlus, U.S. National Library of Medicine, medlineplus.gov/genetics/understanding/basics/gene/.
- “Why Is Sleep Important?” National Heart Lung and Blood Institute, U.S. Department of Health and Human Services, www.nhlbi.nih.gov/health/sleep/why-sleep-important.
- Www.facebook.com/geneticlifehack/. “DEC2 Gene: Short Sleep Mutation.” Genetic Lifehacks, 27 Oct. 2022, www.geneticlifehacks.com/dec2-gene-mutation-that-causes-short-sleep/.
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