A collection of genes that might help explain why some people need a lot more sleep, and others less, than most, has been identified by scientists. The finding provides new clues to how genes for sleep duration are linked to a wide variety of biological processes.

The study, led by scientists with the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, was conducted using fruit fly populations bred to model natural variations in human sleep patterns.

Researchers say a better understanding of these processes could lead to new ways to treat sleep disorders such as insomnia and narcolepsy.

The Elusive Purpose Of Sleep

Study leader Susan T. Harbison, Ph.D., an investigator in the Laboratory of Systems Genetics at NHLBI, said;

“This study is an important step toward solving one of the biggest mysteries in biology: the need to sleep. The involvement of highly diverse biological processes in sleep duration may help explain why the purpose of sleep has been so elusive.”

Scientists have known for some time that, in addition to our biological clocks, genes play a key role in sleep and that sleep patterns can vary widely. But the exact genes controlling the duration of sleep and the biological processes that are linked to these genes have remained unclear.

One potential function of sleep is to conserve resources. Sleep may increase protein synthesis or downscale wake-active synapses. Physical remodeling in the brain during sleep may alter brain plasticity and enable the consolidation of memories.

Metabolic wastes that accumulate during waking may also be eliminated during sleep. If some or all of these activities are accomplished during sleep, it would ensure the balance of proper energetic resources and avoid the accumulation of waste products.

Another possibility is that sleep is crucial for proper development. Babies and young infants spend far more time asleep than their adult counterparts, and interfering with sleep in young animals disrupts critical fitness and cognitive behaviors in adults. These observations suggest that sleep might be a fundamental property of local neuronal physiology, and the need to sleep is established during development with the formation of neuronal structures.

[caption id=“attachment_86146” align=“alignright” width=“318”]sleepy woman Credit: Alexandra E Rust/Flickr[/caption]

Sleep-like behaviors are widely conserved among species, but the type and amount of sleep differs across species. Sleep duration is also variable within a species, with related individuals having more similar sleep than unrelated individuals. This indicates that sleep duration is under at least partial genetic control. Yet sleep parameters can also vary considerably within an individual at different times.

This variation may be driven by ecological demands. For example, during periods of migration over the ocean, frigate birds sleep less often and less intensely. Male pectoral sandpipers sleep little during the competitive mating season, and those that sleep less sleep more intensely. Cetacean mothers and their newborn calves may also have reduced sleep with no apparent effects of sleep loss, though these findings are controversial due to the challenges of observing sleep accurately in these mammals.

In addition, night sleep and sunrise anticipation vary with latitude in flies, suggesting that they are modified by the environment. Taken together, these observations suggest that sleep exhibits environmental plasticity]; that is, sleep can be modified when ecological demands require it. Yet environmental plasticity has an underlying genetic component; thus, genotype influences the amount of adaptation that is possible.

Long Sleepers & Short Sleepers

The researchers wanted to determine how far night sleep duration could be driven up or down in constant environmental conditions using a combination of naturally occurring alleles, and to identify allelic variants responsible for the changes.

To learn more, scientists artificially bred 13 generations of wild fruit flies to produce flies that were either long sleepers (sleeping 18 hours each day) or short sleepers (sleeping three hours each day). The scientists then compared genetic data between the long and short sleepers and identified 126 differences among 80 genes that appear to be associated with sleep duration.

[caption id=“attachment_93886” align=“aligncenter” width=“680”]long or short night sleep duration The response of life history traits to selection for long or short night sleep duration.
(A), percentage flies surviving versus lifespan;
(B), number of flies surviving to the adult stage versus generation of selection;
(C), percentage of males and females surviving sleep assay.
Credit: Harbison ST, et al. CC-BY[/caption]

They found that these genetic differences were tied to several important developmental and cell signaling pathways. Some of the genes identified have known functions in brain development, as well as roles in learning and memory, the researchers said.

Many of these genes could be connected in a single network based on previously known physical and genetic interactions. Candidate genes have known roles in several classic, highly conserved developmental and signaling pathways—EGFR, Wnt, Hippo, and MAPK.

“What is particularly interesting about this study is that we created long- and short-sleeping flies using the genetic material present in nature, as opposed to the engineered mutations or transgenic flies that many researchers in this field are using,” Harbison said. “Until now, whether sleep at such extreme long or short duration could exist in natural populations was unknown.”

The researchers also found that the lifespan of the naturally long and short sleepers did not differ significantly from the flies with normal sleeping patterns. This suggests that there are few physiological consequences — whether ill effects or benefits — of being an extreme long or short sleeper, they said.

The involvement of highly pleiotropic pathway genes suggests that sleep duration in natural populations can be influenced by a wide variety of biological processes, which may be why the purpose of sleep has been so elusive.

The work was supported by the Intramural Research Program of the NIH, The National Heart Lung and Blood Institute.

Harbison ST, Serrano Negron YL, Hansen NF, Lobell AS (2017) Selection for long and short sleep duration in Drosophila melanogaster reveals the complex genetic network underlying natural variation in sleep PLoS Genet 13(12): e1007098. https://doi.org/10.1371/journal.pgen.1007098

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