Scientists have discovered why humans are not nocturnal, revealing that the answer lies in the genes.
Early mammalian ancestors were nocturnal, sleeping during the day while the dinosaurs dominated the land.
However, some mammalian lineages, including human ancestors, independently transitioned to diurnality (active during the day).
How this happened has been a long-standing puzzle, because the brain’s master circadian clock works similarly in both nocturnal and diurnal species.
New research, led by Andrew Beale and John O’Neill at the UKRI MRC Laboratory of Molecular Biology, shows that the crucial difference lies not in the brain’s wiring, but in how individual cells respond to signals in their microenvironment.
Over each 24-hour cycle, small shifts in the body’s internal conditions like temperature or fluid balance subtly influence the chemical reactions inside cells.
These physical cues adjust basic cell processes, such as how proteins are made and modified – core processes that help determine when a cell “expects” day or night.
The team studied cells from both diurnal mammals (including humans) and nocturnal mammals (such as mice).
When exposed to daily temperature cycles, diurnal mammal cells and nocturnal mammal cells shifted their internal circadian clocks in opposite directions. These opposite responses echo the animals’ natural activity patterns.
The researchers found that these contrasting reactions involve two major cellular signalling pathways: mechanistic Target of Rapamycin (mTOR) and With-no-lysine (WNK).
These pathways help cells detect nutrients and regulate fundamental biochemical reactions. Temperature changes caused human and mouse cells to alter protein synthesis and activities in different—and sometimes opposite—ways, pointing to differences in how sensitive their mTOR and WNK pathways are.
Aided by Matthew Christmas, based at the Science for Life Laboratory at Uppsala University, Sweden, the group looked to contextualise this finding against the backdrop of mammalian evolution.
After analysing genetic data across several species, Matthew found that genes within the mTOR and WNK networks have evolved unusually quickly in diurnal mammals. This suggests that the shift from nighttime to daytime activity required evolutionary tuning of basic cellular function at the genetic level.
This discovery suggested that modification of their activity could enable nocturnal mammals to switch to more diurnal activity. To explore this, the group gently altered mTOR activity in nocturnal mice using diet-based treatments.
Once mTOR function was reduced, the mice began behaving more like diurnal animals, shifting their active hours into the daytime. This underlined that changes in cellular pathways can influence when an animal is active, functioning like a day/night switch.
John explained: “Understanding why humans are diurnal while many other mammals are not shines new light on our circadian rhythm, part of our biology that is important for long-term health.
“Our research leverages an evolutionary approach to reveal the fine details of how fundamental cellular pathways sense and respond to daily environmental rhythms. These differ between species in ways we simply hadn’t appreciated before.”
Their findings also highlight how climate change could impact mammal behaviour as they adapt to transforming conditions.
Andrew added: “As the atmosphere warms up, the current relationship between the external environment and food availability is rapidly changing. As a result, many mammals may shift the time of day they are active. This could have wide-ranging and detrimental effects on whole ecosystems.”
The work was funded by UKRI MRC, UKRI Future Leaders Fellowship, the Wellcome Trust and the Royal Society.
Paper: A cellular basis for the mammalian nocturnal-diurnal switch by Andrew D. Beale, Matthew J. Christmas, John S. O’Neill et al in Science.
The Medical Research Council is at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health.
Thirty-three MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed.
