As long as the diurnal dinosaurs dominated the earth, all mammals were nocturnal. This only changed after the large predators became extinct. As a result, different mammal lineages became independently diurnal. But how could this change work even though the central internal clock in the brain remained largely unchanged? A study now shows that the day-night switch is encoded in the signaling networks of our cells. If the researchers inhibited the signaling pathway in mice, the animals, which are actually nocturnal, became active during the day.
The most important clock for our day-night rhythm is located in the brain in a region called the suprachiasmatic nucleus. This region is very similar in all mammals, whether they are active during the day or at night. This central control is supplemented by numerous other internal clocks in our cells. These are based on circadian genes that are active differently depending on the time of day and in this way control when we become tired or hungry, for example. Our internal clocks are synchronized by various influencing factors, including the light perceived through the eyes, food intake and body temperature.
But why do the same signals cause opposite reactions depending on the animal species? Why do some animals retreat to sleep in the dark, while others only really get fit then? And how were the circadian rhythms of many mammals able to switch from nocturnal to diurnal activity within evolutionarily short periods of time after the extinction of the dinosaurs?
Opposite synchronization
Researchers led by Andrew Beale from the MRC Laboratory of Molecular Biology in Cambridge, Great Britain, have now gotten to the bottom of these questions. To do this, they first cultured cells from mice, a nocturnal species, and humans, a diurnal species. They simulated the daily fluctuations in body temperature and observed the activity of circadian genes.
The result: In the cells of both species, the temperature fluctuations synchronized the cellular internal clocks – albeit in opposite phases. “The temperature change triggered opposite shifts in global protein synthesis and phosphorylation in human and mouse cells,” the team reports. In human cells, lower temperatures, which typically occur at night, led to lower activity of important circadian rhythm proteins. In mouse cells, however, lower temperatures stimulated activity. The same result was seen in the cells of other diurnal or nocturnal mammals, including nocturnal rats and lemurs and diurnal sheep and marmoset monkeys.
Daytime activity can save energy
Further analysis revealed the underlying mechanisms at the molecular level. Accordingly, the so-called mTOR signaling pathway forms a kind of cellular day-night switch. If the researchers blocked this signaling pathway in mice, their activity phase shifted from night to day. The same effect occurred when the mice were given too little to eat. In this case, their bodies shut down the mTOR signaling pathway and the animals began to forage for food during the day.
From an evolutionary perspective, this can be a life-saving mechanism: nocturnal activity carries a lower risk of being eaten by predators, but requires more energy to compensate for the loss of heat in the cold night. “Daytime activity can represent an energy-saving measure that outweighs the risk of predation when food is scarce,” explains the research team. Instead of sacrificing valuable energy searching for food under the cover of night, it can make sense if resources are limited to choose the slightly riskier but more energy-saving option during the day.
New temporal niche
After the extinction of the dinosaurs and the disappearance of their most dangerous predators, daytime activity offered early mammals a new ecological niche. Comparing the genomes of different species shows that the genes that regulate the mTOR signaling pathway have evolved more quickly in diurnal mammals than in nocturnal mammals – an indication of their great evolutionary importance. In addition, the genes involved in diurnal mammals are less sensitive to temperature fluctuations. “This is also consistent with an energy-saving adaptation,” write the researchers. “These results reveal a genetic and biochemical basis for the switch from nocturnal to diurnal activity and highlight how cellular signaling networks can encode complex phenotypes such as temporal niche selection.”
The new findings could also be medically relevant: “Understanding how diurnal mammals integrate the same environmental signals to achieve a reversal of organismic and cellular physiology compared to nocturnal mammals is crucial for understanding internal synchrony, which is central to long-term health,” explains the research team.
Source: Andrew Beale (MRC Laboratory of Molecular Biology, Cambridge, UK) et al., Science, doi: 10.1126/science.ady2822