A new study, published today in the Science Journal, reveals that the answer is 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).
Cellular response
How this happened has been a long-standing puzzle, because the brain’s master circadian clock works similarly in both nocturnal and diurnal species.
The new research 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.
Circadian clocks
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, led by Andrew Beale and John O’Neill at the Medical Research Council (MRC) Laboratory of Molecular Biology, 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.
Breakthrough
These opposite responses echo the animals’ natural activity patterns.
The researchers found that these contrasting reactions involve two major cellular signaling pathways:
- mechanistic target of rapamycin (mTOR)
- with-no-lysine (WNK)
These pathways help cells detect nutrients and regulate fundamental biochemical reactions.
Differing reactions
Temperature changes caused human and mouse cells to alter protein synthesis and activities in different, and sometimes opposite, ways.
This points 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.
‘Evolutionary tuning’
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.
The evidence
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 or night switch.
Understanding human biology
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.
Climate change
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.
This work was funded by:
- MRC
- Future Leaders Fellowships
- Wellcome Trust
- Royal Society
