A type of “cheat sheet” inside cells that describes how to translate a series of nucleotides (“letters”) in DNA or RNA into a sequence of amino acids (“pieces”) that make up proteins is called the genetic code. The device is the same in almost all organisms on Earth, but scientists are still arguing about the time of its origin and gradual changes. Now researchers have revised established ideas about its origin by analyzing parts of the protein chain of this ancient genetic “cheat sheet.”

The universal genetic code allows DNA and RNA chains consisting of four types of nucleotides to be converted into protein sequences consisting of 20 amino acids. This complex process arose in stages and evolved gradually, and previous attempts to establish a clear “chronology” of the appearance of amino acids in the genetic code were mostly based on data on the chemical availability of compounds in pre-biological conditions.

In particular, the famous Miller-Urie experiment showed that lightning strikes in the Earth’s atmosphere in the distant past could lead to the formation of organic molecules that, together with rain, entered the so-called “primordial broth”. It turns out that simple and small amino acid molecules are preferred in early life (and larger and more complex amino acids join the code later).

Authors of the scientific study published in the journal PNASHe presented a new assessment of the order of inclusion of amino acids in the genetic code, based not on abiotic factors (temperature, light, humidity, chemical composition of the air and aquatic environment), but briefly on the analysis of protein domains. They are stable parts of the protein chain that can function and evolve independently, emerging from the last universal common ancestor (LUCA).

A team of scientists led by Sawsan Wehbi performed a comparative phylogenetic analysis of thousands of LUCA-related protein domain families and reconstructed their amino acid sequences. The method made it possible to determine how not only environmental conditions, but also the actual needs of organisms affect the order in which amino acids are added to the genetic code.

It turns out that simpler and smaller amino acids became part of the universal genetic code earlier than scientists thought. The same applies to metal-bound and sulfur-containing amino acids (e.g. cysteine, methionine and histidine). It turns out that metalloenzymes and sulfur-containing protein components played a critically important role in the beginning of the evolution of cellular metabolism.

At best, the modern genetic code may have emerged after the disappearance of older variants. The fact is that among the domains that appeared before LUCA, an increase in the content of aromatic amino acids such as tryptophan and tyrosine was observed, although they were traditionally considered “late newcomers”.

The text of the scientific work also states that the order of inclusion of amino acids in the genetic code may have been disrupted as part of laboratory experiments (the latter does not always adequately reflect the real conditions in old cells). This suggests that other amino acid coding systems may have existed before the emergence of the modern genetic code, dating back to geological time. The authors of the new study concluded that early life had “loved” ring structures.

Thus, geneticists were able to revise the order of formation of the universal genetic code; This showed that this is not entirely determined by the abiotic availability of amino acids, but occurs under the influence of metabolic and structural properties of ancient cells. The results obtained are important for understanding the processes that contributed to the emergence of life on Earth and will help in the search for life beyond our planet.