Unveiling the role of selenocysteine, the mysterious 21st amino acid

All the cells of an organism contain a copy of DNA in their nucleus. In order to implement the instructions it contains, this DNA must be copied into an RNA molecule, which reaches the ribosomes, which in turn read this information and synthesise proteins. The codons, animo acid triplets that form proteins and are the markers the ribosomes need to know how to produce each protein, are key in this transition process. There exist a total of 61 codons that code for 20 amino acids, and three codons that act as stop signals in the translation process.

Nevertheless, certain organisms use an extra amino acid, selenocysteine, dubbed the 21st amino acid, which lacks its own codon and uses a stop codon after modifying it. For this purpose, it avails itself of complex machinery, with specific enzymes and RNA; this process can prove to be very costly for the cell. But why? What function does this amino acid have in proteins? Why is it present in humans and in the other vertebrates whereas, on the other hand, other species have lost it? Now, researchers from the Centre for Genomic Regulation (CRG) in Barcelona, part of the Barcelona Institute of Science and Technology, in collaboration with CRG Alumni Marco Mariotti and Vadim N. Gladyshev, from the Harvard Medical School (USA), and Gustavo Salinas from the University of the Republic in Uruguay, have shed some light on these questions.

“In previous studies, we discovered that the machinery of selenocysteine had been lost many times in the course of evolution and we began to take an interest in why it disappears so easily in some groups but not in others”, explains the ICREA Research Professor Toni Gabaldón, head of the CRG’s Comparative Genomics group.

The fungi were the only organism kingdom in which a species with selenocysteine had never been found, and the researchers decided to focus on them, leveraging the recent publication of a thousand fungi genomes in public-access databases. On analysing them, they discovered, as they reported in the article published in Nature Microbiology, that nine of the 1,000 species actually did have this amino acid.

“It came as a surprise to us, because no fungi were believed to have selenocysteine”, says Gabaldón, which explains why the nine species they discovered that did have it belong to relatively unsequenced groups of fungi that “diverged at an early stage in the evolution of fungi, which means that we will probably find more cases of selenocysteine when more genomes of these groups are sequenced”.

The ancestor of the fungi that they have identified with this amino acid also had it. Certain lineages have retained it, whereas others have lost it, which could also be the case in other organisms. “The question that remains to be answered is why it is lost in some organisms whereas in others these genes are essential”, says Gabaldón. “Understanding why selenocysteine is important in fungi and other branches of the tree of life may help us to understand why it is so important to our species and to define what makes selenium essential to human health”, he concludes.

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