Image: Seanmcgrath, WikimediaThe circadian clocks that control and influence dozens of basic biological processes have an unexpected "snooze button" that helps cells adapt to changes in their environment.


“This provides organisms with a novel and previously unappreciated mechanism for responding to changes in their environment,” says Prof. Carl Johnson. He and Associate Prof. Antonis Rokas collaborated on the study.



“While biological clocks are vital to maintaining healthy patterns of sleep, metabolism, physiology and behavior, under certain environmental conditions strict adherence to these rhythms can be disadvantageous,” says Michael Sesma of the National Institute of General Medical Sciences, which partially funded the work. “This work shows how organisms can ignore the clock under certain circumstances — much like hitting a biological snooze button on the internal timepiece — and enhance their survival in the face of ever-changing circumstances.”


It turns out that there is a reason for this redundancy. Some codons are faster and easier for cells to process and assemble into proteins than others. Recognition of this difference led to the concept of optimal codons and the hypothesis that natural selection should drive organisms – particularly fast growing ones – to use genes that use optimal codons to make critical proteins that need to be highly abundant or synthesized rapidly in cells.



In the cyanobacteria, however, the researchers observed a different phenomenon. At Vanderbilt, Research Associate Prof. Yao Xu optimized the codons in the cyanobacteria’s biological clock. This did not shut the clock down in the algae, but it did have a more subtle, but potentially as profound effect: it significantly reduced cell survival at certain temperatures.

“Xu figured that the biological clock with optimized codons might work better at lower temperatures and it did,” Johnson says. However the substitution also modified the biological clock so it ran with a longer, 30-hour period. When forced to operate in a 24-hour daily light/dark cycles, the bacteria with the optimized clock grew significantly slower than "wild-type" cells. “In cyanobacteria, it’s as if writing speed changes the meaning,” says Rokas.


“It is now clear that variations in codon usage is a fundamental and underappreciated form of gene regulation,” says Rokas.

Recognition of the importance of this process has a number of potential applications in biotechnology. For example, “it should be possible to improve the ability of algae to robustly express biofuel-producing proteins from other organisms by optimizing the codons that they use,” Johnson says.