The circadian clocks that control and influence dozens of basic biological processes have an unexpected control mechanism that helps cells adapt to changes in their environment. A new study provides 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.
For a long time, biologists thought that these synonyms (synonymous codons) were in fact interchangeable. Recently, they have realized that this is not so, and that differences in synonymous codon usage have a significant impact on cellular processes. A codon consists of a sequence of 3 DNA nucleotides, each of which can be one of 4 different molecules, yielding 64 possible codons, 61 of which specify one of 20 possible amino acids that can be used to build proteins. Different codons that correspond to the same amino acid are effectively synonyms - or so it seemed.
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 to use genes that use optimal codons to make critical proteins that need to be highly abundant or synthesized rapidly in cells.
The problem with this hypothesis was shown in a new study of the effect of changing codon usage on the simple biological clock found in single-celled cyanobacteria (blue-green algae). In the cyanobacteria the researchers observed that optimizing the codons in the cyanobacteria’s biological clock did not shut the clock down, but it did have a more subtle, potentially as profound effect: It significantly reduced cell survival at certain temperatures. The biological clock with optimized codons worked better at lower temperatures. 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. “It is now clear that variations in codon usage is a fundamental and underappreciated form of gene regulation,” said researcher Antonis Rokas.
• When it comes to genetic code, researchers prove optimum isn’t always best
• Manipulation of biological clocks teaches an important lesson