Even our genes may be slaves to the rhythm of night and day. Evidence is emerging that the 24-hour circadian cycle governs the expression of virtually all our genes, signalling a fundamental shift in our understanding of how genes function.
Using lab-on-a-chip microarrays, Andrey Ptitsyn of Colorado State University, Fort Collins, and colleagues monitored oscillations in the activity of 20,000 mouse genes over two days. “We could not find a single gene that did not oscillate,” Ptitsyn says (PLoS Computational Biology, DOI: 10.1371/journal.pcbi.0030120). This was a surprise: while it was known that changes in the light-dark cycle can affect how genes are expressed, this was thought only to apply to around 15 per cent of them.
The team found that different sets of genes peak and trough in sync within the same organ, though not necessarily within different tissues. The genes with the clearest circadian rhythm seemed to be those that control energy metabolism, and Ptitsyn suggests that they may be responsible for setting the rhythms of other sets of genes.
Advertisement
When not exposed to a light-dark cycle, genes still oscillated, but in an increasingly uncoordinated way, drifting apart like an orchestra without a conductor. In some organs, the level of expression of some genes appears to be kept constant by having two copies working in tandem, like shift workers, so that when one is off, the other is on.
The findings suggest that interfering with the body’s circadian rhythm could have profound effects, particularly on multi-gene traits such as mood, growth and immunity. “Everyone who diets knows you shouldn’t eat late, and now we are getting closer to understanding why,” Ptitsyn says. His team found daily oscillations in genes governed by the hormone leptin, which usually decreases appetite. He suggests the body’s response to food may depend on whether these genes are switched on when leptin is released. “This is perhaps a trivial example,” he says, but the effects could be important in every aspect of health.
He speculates that artificial light could be having hitherto unsuspected effects. “We have only had artificial lighting for maybe 100 years,” Ptitsyn points out, so this might have something to do with the recent rise in obesity.
The findings have implications for studies of how genes work and regulate each other. Even those normally thought to be silent showed slight activity when studied over a 24-hour cycle. “It’s a pilot-light level of activity,” Ptitsyn says. Researchers trying to establish the role of particular genes should not just take a snapshot of their activity, but monitor them over a prolonged period, he says.
