Could There Be a Genetic Reason for the Need to Sleep?

The need to repair damaged DNA may be the reason we sleep.

Posted Sep 30, 2019

One of the great unsolved mysteries of sleep is, why do we sleep? Why do we need to spend about a third of our lives in a vulnerable, unconscious state? Clearly, we cannot function effectively without it and yet could nature not have found some other way to renew mental functioning without needing to disconnect from the environment so completely? And yet, sleep is seen in all animals, not just humans. Even the fruit fly has periods of quiescence that appear to be sleep and can be used for research to better understand the processes that underlie sleep in other animals, including humans (Cirelli & Bushey, 2008). It seems that sleep would be counterproductive, increasing the risk of predation and decreasing the rate of survival in unconscious and minimally responsive creatures. Yet, despite many millions of years of evolution, sleep persists. It seems that it must perform some extremely important function that biology has not yet found a way to do while maintaining full conscious contact with the external environment. A recent study (Zadaet al,2019) suggests that there may be strong genetic reasons for the need to sleep.

A number of important brain functions are carried out during sleep and this has given rise to a number of theories about the purposes of sleep. For example, it is possible that sleep emerged as a method of energy conservation. Furthermore, sleep seems to function to reduce synaptic connections during the night, providing a “clean slate” to start the next day. More recently, the important role of sleep in memory and learning processes has emerged. Still, none of these important functions appear to be something that could not be accomplished while allowing the organism to remain alert and safe.

Since DNA is an active molecule and subject to constant change due to processes such as cell division and protein synthesis, damage naturally occurs that must be repaired (Featherstone & Jackson, 1999). This damage can occur from the creature simply exploring an environment or learning something new. In other words, given the genetic mechanism at the basis of earthly life as we know it, significant damage to DNA is inevitable and cannot be prevented. It must, however, be repaired rapidly, as damaged DNA is unable to effectively carry out its functions and could even lead to the development of diseases such as cancer (Featherstone & Jackson, 1999; Jackson, 2002). DNA double-strand breaks (DSB) are a significant type of DNA damage and are caused by factors such as ionizing radiation, respiratory metabolism, certain chemotherapy drugs, and certain types of cell division (Jackson, 2002). DSB must be quickly repaired and there are a number of mechanisms by which cells accomplish this (Lieber, 2010).

Neuronal activity, such as that which inevitably occurs during wakefulness, increases the formation of DSB (Zada et al, 2019). Zada et al (2019) hypothesized that sleep provides an opportunity for neurons to engage in maintenance of DNA. Their study employed manipulation and observation of chromosomal markers in single cells of live zebrafish. Of note, Zada et al (2019) were able to show that chromosome dynamics were decreased during wakefulness and increased during sleep but only in neurons and not in other types of cells. Thus sleep may be needed in order to recover from the chromosomal damage that naturally occurs in neurons during wakefulness. Interestingly, they proposed that increased chromosome dynamics could be used as the definition of sleep, in a single neuron.

"Yin and Yang" by Klem - This vector image was created with Inkscape by Klem, and then manually edited by Mnmazur.. Licensed under Public Domain via Wikimedia Commons
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Source: "Yin and Yang" by Klem - This vector image was created with Inkscape by Klem, and then manually edited by Mnmazur.. Licensed under Public Domain via Wikimedia Commons

References

Cirelli, C., & Bushey, D. (2008). Sleep and wakefulness in Drosophila melanogaster. Annals of the New York Academy of Sciences, 1129, 323–329. doi:10.1196/annals.1417.017

Featherstone, C. & Jackson, S.P., (1999). DNA double-strand break repair. Current Biology, 9 (20), p R759 – R761.    

Lieber, M.R. (2010). The Mechanism of Double-Strand DNA Break Repair by the Nonhomologous DNA End Joining Pathway. Annual Review Biochemistry. 79: p181–211. doi:10.1146/annurev.biochem.052308.093131.   

Jackson, S.P. (2002). Sensing and repairing DNA double-strand breaks. Carcinogenesis, 23 (5), p 687–696, https://doi.org/10.1093/carcin/23.5.687        

Zada, D., Bronshtein, I., Lerer-Goldshtein, T., Garini, Y., Appelbaum, L. (2019). Sleep increases chromosome dynamics to enable reduction of accumulating DNA damage in single neurons.  Nature Communications, 10 (895). https://doi.org/10.1038/s41467-019-08806-w