Cracking the evolutionary code of sleep

A groundbreaking new study from Bar-Ilan University shows that one of sleep’s core functions originated hundreds of millions of years ago in jellyfish and sea anemones, among the earliest creatures with nervous systems. By tracing this mechanism back to these ancient animals, the research demonstrates that protecting neurons from DNA damage and cellular stress is a basic, ancient function of sleep that began long before complex brains evolved.

Although sleep is universal among animals with nervous systems, it poses clear survival risks: during sleep, awareness of the environment diminishes, leaving animals more exposed to predators and interrupting vital behaviors such as feeding and reproduction. The persistence of sleep across evolution has therefore been one of biology’s enduring enigmas. According to this study, sleep’s indispensable function emerged early in animal evolution and is so crucial that it outweighed its inherent dangers.

The study was jointly led by Prof. Lior Appelbaum’s and Prof. Oren Levy’s laboratories at Bar-Ilan University. In previous research, the Appelbaum Lab showed in zebrafish that neurons accumulate DNA damage during wakefulness and require sleep to recover, highlighting the need to reduce DNA damage as a fundamental driver of sleep. DNA damage can arise from multiple sources, including neuronal activity, oxidative stress, metabolism and radiation. While DNA damage can be harmful to all cells, neurons require sleep to avoid genome insults, possibly because they are unique non-dividing excitable cells.

In the current study, published today in Nature Communications, Dr. Raphael Aguillon, Dr. Amir Harduf and colleagues from the Appelbaum and Levy labs defined and characterized sleep patterns in two ancient animal lineages: diurnal, symbiotic jellyfish that sleep at night and shortly nap at mid-day, and crepuscular, non-symbiotic sea anemones that sleep from dawn through the first half of the day. Using infrared video tracking and behavioral analysis, they observed that both creatures sleep roughly eight hours daily, similar in duration to human sleep. Despite their different lifestyles and mechanisms controlling sleep, they share a common pattern: DNA damage accumulates in neurons during wakefulness and is reduced during sleep. When the animals were kept awake and DNA damage increased, they slept longer afterward. This behavior, known as sleep rebound, enabled recovery and reduction of DNA damage levels.

The study also showed that increasing DNA damage, either through UV radiation or exposure to a DNA-damaging chemical, triggered recovery sleep in both species. Conversely, promoting sleep with the hormone melatonin reduced DNA damage. These findings reveal a bidirectional relationship in which DNA damage increases sleep need, and sleep, in turn, facilitates damage reduction, suggesting that protecting neurons from daily cellular stress and DNA damage may have been the evolutionary driver of sleep.

The two basal animals also reveal how sleep is regulated differently. While homeostatic sleep pressure (a built-in need for sleep) regulates sleep in both species, sleep is mainly controlled by the light-dark cycle in the jellyfish. In contrast, the sea anemone relies mostly on its internal circadian clock. However, despite these differences, both animals depend on sleep to reduce DNA damage and cellular stress, whether their sleep/wake cycle is driven by sunlight or by internal timing.

“Our findings suggest that the capacity of sleep to reduce neuronal DNA damage is an ancestral trait already present in one of the simplest animals with nervous systems,” said Prof. Lior Appelbaum, principal investigator of the Molecular Neuroscience Lab at the Faculty of Life Sciences and Multidisciplinary Brain Research Center at Bar-Ilan University. “Sleep may have originally evolved to provide a consolidated period for neural maintenance, a function so fundamental that it may have been preserved across the entire animal kingdom.”

The study also has important implications for human health. Sleep disturbances in humans are associated with cognitive decline and an increased risk of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, which may involve chronic accumulation of neuronal DNA damage. The evolutionary evidence provided by this research strengthens the link between sleep quality and long-term brain resilience.

“Sleep is important not just for learning and memory, but also for keeping our neurons healthy. The evolutionary drive to maintain neurons that we see in jellyfish and sea anemones is perhaps one of the reasons why sleep is essential for humans today,” concluded Prof. Appelbaum.

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