Body clock has “snooze button” to help cells adapt

Researchers from Vanderbilt University have found that the 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," said Professor of Biological Sciences Carl Johnson. He and Associate Professor of Biological Sciences Antonis Rokas collaborated on the study.

Like many written languages, the genetic code is filled with synonyms: differently spelled "words" that have the same or very similar meanings. For a long time, biologists thought that these synonyms, called synonymous codons, were in fact interchangeable. Recently, they have realized that this is not the case and that differences in synonymous codon usage have a significant impact on cellular processes, so scientists have advanced a wide variety of ideas about the role that these variations play.

The basic letters of the genetic code are a quartet of molecules (nucleic acids) designated A, C, G and U. These are combined into 61 triplets called codons, which are similar to words. The codons provide the blueprints that the cell's protein-building machinery uses to generate amino acids, which are the basic building blocks that make all the proteins found in living organisms. However, cells only use 20 amino acids. That means a number of amino acids are produced by several different codons. For example, CCA, CCG and CCC are synonymous codons because they all encode for the same amino acid, proline.

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.

The study published online Feb. 17 by the journal Nature, involved Research Associate Professor Yao Xu, optimizing the codons in the biological clock of cyanobacteria or algae. 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 said. 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," said Rokas.

The study provides compelling new evidence that at least some species can alter the way that their biological clocks function by using different "synonyms" that exist in the genetic code.