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Renewed cracking of the genetic code – we may have just begun to scratch the surface



  DNA Molecule

Researchers identified changes in the genetic code used to convert DNA into protein. Credit: Tomislav Alajbeg

When you open a biology textbook, you will find a standard molecular biology symbol: the table summarizing the standard genetic code. This refers to the set of rules according to which the cell "decodes" the information contained in DNA and "translates" it into the amino acids that make up proteins. For example, the codon (3 letter DNA sequence) "AGA" in almost all organisms directs the translation machinery to add the amino acid asparagine. While some deviations in the genetic code used by various organisms are known, studies published earlier this year in Molecular Biology and Evolution and in the current issue of Genome Biology and Evolution We have come close to suggesting that the number of variations in the genetic codes of all living organisms may have begun to scratch the surface.

In the April issue of Molecular Biology and Evolution has a group of researchers, including Emmanuel Noutahi, Virginie Calderon, Mathieu Blanchette, Nadia El-Mabrouk and Bernd Franz Lang from the University of Montreal, the Institute Research Centers at Montreal and McGill University have published an analysis of the mitochondrial genomes of 51

green algae and land plants (Noutahi et al., 2019). This analysis was based on a newly expanded version of the CoreTracker bioinformatics tool previously developed by this group (Noutahi et al., 2017). CoreTracker identifies differences between a DNA sequence and the expected amino acid based on the amino acids commonly found at this position in closely related species. With this tool, Noutahi and colleagues identified 14 new codon rearrangements, replacing one amino acid with another, most of which was found in an algal group known as Sphaeropleales. These algae have an unusual mitochondrial genome organization that seems to lie between the larger genomes and the compact, derived genomes of some of their relatives.

According to the authors, the field of evolution of the genetic code is characterized by a rapid increase in genome data (genomes plus corresponding transcriptomes). "Comparative / evolutionary bioinformatics methods such as CoreTracker can now not only predict deviations of the genetic code, but also provide clues to the underlying mechanism." In fact, given their results, the researchers suggest that the genetic code deviations in the Sphaeropleal mitochondria actually contributed to their unusual genome organization. Based on this theory, after the migration of some mitochondrial genes into the nuclear genome during the genome reduction process, "UCA" (normally coding for the amino acid serine) was assigned a termination codon. This would have made it impossible to transfer additional mitochondrial genes into the nucleus, resulting in a mitochondrial genome that was medium in size.

Prior to the publication of the article by Noutahi et al. The researchers David Zihala and Marek Elias from the University of Ostrava have independently discovered the large number of changes to the genetic code in the Sphaeroplealen. Following Elijah's discovery of new genetic codes in multiple protists by chance, Zihala and Elias were motivated to perform a systematic screening to find possible additional cases of organisms with new genetic code variants or previously missed deviations from the standard genetic code. " Like Noutahi et al. Their methods included the identification of discrepancies between DNA sequences and expected amino acids based on sequences present in related genomes, although they also performed some manual curation.

The analysis of Genome Biology and Evolution (Zihala and Elias 2019), published in the current issue, identified several more codon remaps in the Sphaeroplates, as they included a wider selection of this group. Otherwise, the results of the two studies were very congruent despite the somewhat different methods. In addition to the genetic code changes, Zihala and Elias also identified mutations in a mitochondrial release factor-a protein that recognizes termination codons-that, according to Elias, "are related to the intriguing ability of some sphaeroplal mitochondria to terminate translation at codons, usually as coding for an amino acid to be read. We therefore offer the first specific hypothesis for the molecular basis of this unusual ability.

Overall, the results of both studies highlight the need for a deeper awareness of genetic code discrepancies throughout the tree of life. Otherwise, the use of a wrong code in deriving protein sequences from DNA sequences can lead to inaccuracies in predicted protein sequences used for both phylogenetic and molecular biological analyzes. In addition, Noutahi and colleagues found that "the two publications were able to predict specific changes in the meaning of codons using publicly available data, without biochemical experiments and with high certainty."

However, they also note that both statements are true Studies are purely computerized and "this type of & # 39; paper biochemistry & # 39; has its limits. Only evolutionarily well-established cases of codon evolution can be deduced (ie, without cases of initial or incomplete stages), and although changes in tRNA repertoire, structure, and specificity can be deduced to some extent, biochemical confirmation critically required. This limitation was also pointed out by Elias, who noted that his group wanted to use proteomics methods to validate some of their bioinformatic predictions regarding the various presumably reassigned codons. "Unfortunately," Elias continues, "non-standard genetic codes are usually found in organisms that are difficult to detect by direct biochemical or genetic methods, so it remains challenging to back up the molecular mechanisms better understand the observed codon changes. " importance. "

Future investigations will almost certainly reveal additional, as yet unidentified changes in the genetic code in various organisms. Indeed, Elias notes, "We are also analyzing some exciting new cases of genetic code modification in core genomes of certain obscure protists revealed by our survey of publicly available sequence data." In addition, the authors of Noutahi et al. The study indicates that "as this field evolves due to an increasing number of reports of deviations from the standard genetic code, particularly for eukaryotes and their organelles, the path to understanding codon evolution with all of them Mechanistic implications have just begun.

Literature:

"Rapid Genetic Code Evolution in Mitochondrial Genomes of Green Algae" by Emmanuel Noutahi, Virginie Calderon, Mathieu Blanchette, Nadia El-Mabrouk and Bernd Franz Lang, January 29, 2019, Molecular Biology and Evolution .
DOI: 10.1093 / molbev / msz016

"Evolution and Unprepared Variants of the Mitochondrial Genetic Code in a Line of Green Algae" by David Žihala and Marek Eliáš, October 16, 2019, Genome Biology and Evolution .
DOI: 10.1093 / gbe / evz210


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