What does codons

Genetic code: "Stop" does not always mean "Stop"

In language, for a word with multiple meanings, the correct meaning can be deduced from its context. As human language evolves, words can change their meaning too. Biology also has a language with which it conveys information: the genetic code is something like the universal language of life and applies to all living beings - from the simplest bacteria to the human body. The genetic code specifies how a sequence of DNA (deoxyribonucleic acid) is translated into amino acids. Amino acids are the building blocks of proteins. In this way, the blueprint of a protein can be read from a section of DNA - a gene - and implemented.

The genetic code is extraordinarily stable: since it was created around 4 billion years ago, it does not seem to have changed during evolution. There are always three "letters" in DNA that code for a specific amino acid. There are a total of 61 “words” in this biological language, as well as three so-called stop codons, the “closing points”: They define the end of a sentence and thus the end of protein production. There is clarity in the genetic code, there is no ambivalence here - that was the doctrine up to now. Researchers at the Institute for Cell Biology at the University of Bern have now discovered that a codon has several meanings. Her research objects are ciliate animals, unicellular organisms that are found in almost all bodies of water. This discovery in the genetic code of ciliates represents a previously unknown intermediate step in evolution. The results of the study have now been published in the journal "Cell".

Dogma has been proven wrong

"When we examined the genetic code of numerous ciliate species, we found that two species seemed to have stop codons everywhere in their code," says Prof. Mariusz Nowacki from the Institute of Cell Biology, head of the study. For a ribosome, the cell machine that reads the code and translates it into proteins, it would look like sentences with a period after every other word. The researchers quickly realized that these “final points” had to have another meaning. In fact, it is already known that stop codons can, in rare cases, induce the production of an amino acid in ciliate animals - although the actual "end of sentences" are communicated differently.

To their surprise, Nowacki's researchers found that some of these stop codons actually say “stop” and clearly convey to the ribosomes that they should stop producing protein. "We conclude from this that these codons are read depending on the respective context," says Nowacki. In doing so, the researchers are overturning the dogma of the genetic code that the “words” only have a single meaning. Further analyzes showed that structural properties at the end of the coding sequence dictate how the ribosome “understands” the three-letter word - but how the ribosome can read this context precisely is still unclear.

Ambivalent or not?

"We did not originally agree on these codons as to whether we should call them 'ambivalent'", says Nowacki. Because the context gives clear indications of how the codon should be interpreted. The biological language is thus clear - the ribosome "knows" very well how to deal with the various meanings. "Just as we don't confuse a Volkswagen Golf with the sport, the context here also provides enough information to understand the correct meaning," explains Nowacki. Instead, the researchers prefer to speak of “context-dependent” codons.

According to the cell biologist in Bern, these results are not only interesting because they show that simple truths in cellular mechanisms often turn out to be invalid. Nowacki suspects that his team unintentionally discovered a “transition stage” in the evolution of this specific cell mechanism - and, so to speak, observed evolution as it emerged. Investigating this anomaly further could help biologists better understand how the genetic code gradually evolves in some species of living being. "Apparently the biological language is not as‘ frozen ’as we thought," says Nowacki.

This study was partially supported by the National Research Center (NCCR) RNA & Disease, which is funded by the Swiss National Science Foundation (SNSF). The NCCR RNA & Disease brings together over 30 Swiss research groups that deal with various aspects of RNA biology and the role of RNA in disease mechanisms. The NCCR is managed by the University of Bern and the ETH Zurich.

Publication information

Estienne Carl Swart, Valentina Serra, Giulio Petroni, Mariusz Nowacki: Genetic Codes With No Dedicated Stop Codon: Context-Dependent Translation Termination, Cell, Volume 166, Issue 3, p691–702, July 28, 2016, doi: http: // dx.doi.org/10.1016/j.cell.2016.06.020