A new DNA created in the laboratory duplicates the genetic alphabet

Source: El País
The artificial structure has eight ‘letters’ and can store biological information and evolve
All the information necessary to assemble and operate a living being, from its most basic molecular components, is collected in a chop written with only four letters. The text is the complete genome of the organism. The alphabet is the so-called nitrogenous bases, paired chemical units that form each rung in the double helix of DNA: adenine (A) with thymine (T) and cytosine (C) with guanine (G).

With these four letters, the mechanisms of evolution have written the instructions of organisms as diverse as a bacterium, an oak, an elephant or a person. Now, a team of scientists led by the Foundation for Applied Molecular Evolution, in the US, has expanded the alphabet to include four new letters (Z, P, S and B). They have christened the resulting structure hachimoji, which means «eight letters» in Japanese, and is described in the number last week in the journal Science.

The work is partially funded by NASA and «is a very big conceptual advance,» says Víctor de Lorenzo, an expert in microbiology and synthetic biology at the National Center for Biotechnology (CNB-CSIC). De Lorenzo, oblivious to the new study, explains that with this achievement you can explore biological systems that have never appeared. Natural DNA has the four letters that it has for «a series of historical contingencies», then a different biochemical foundations could lead to a completely different life. «The release of the dice could have fallen otherwise,» he summarizes.

THE FOUR NEW ‘LETTERS’ IN THE GENETIC ALPHABET

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The scientists created the new nitrogenous bases introducing small modifications to the structures of the four natural bases. As with A, T, C and G, the synthetic letters are also grouped into two pairs because, when facing the complementary bases (Z with P and S with B), they form chemical bonds called hydrogen bonds. In a series of experiments, the research team has shown that the double helix that forms hachimoji DNA is stable.

However, De Lorenzo warns that it is premature to talk about a new genetic code, since the introduced letters do not constitute an encryption of other biomolecules, as it does with the four usual nitrogenous bases. Classic DNA is useful for life and can evolve by natural selection because it is transcribed into corresponding molecules of RNA (simple chains of nitrogenous bases) and these are translated into proteins (chains of amino acids). Generally, proteins are biomolecules that perform the functions necessary for life.

In the natural system, every three nitrogenous bases correspond to an amino acid, and therefore form a code. Not so with hachimoji DNA, which produces viable RNA but does not have a valid translation in the form of proteins. Theoretically, that translation could be achieved, because the necessary knowledge and technique were developed years ago.

Since there are only 20 amino acids but the four classical genetic letters can be combined in 64 different triplets, there are superfluous DNA «words» to which scientists have been able to assign new meanings, corresponding to synthetic amino acids. «We did that two decades ago,» says Steven Benner, the lead author of the paper. «In this particular study, we did not use the new letters of the genetic alphabet to create words in the lexicon of proteins.»

Evolution to catch cancer
Even so, Benner and his colleagues argue that the hachimoji system meets the requirements of a living system and capable of evolving, because it produces a type of RNA that adheres to other molecules and performs some functions analogous to those of proteins. For example, Benner’s team discovered, when it only had a six-letter system, that some RNA sequences rich in Z and P bases stick easily to certain cancer cells. That could serve, for example, as a diagnostic tool.

«By increasing the genetic alphabet to eight, we have improved the system’s ability to evolve,» says Benner. The four new bases include molecular groups with greater biochemical activity than conventional bases. «The potential to create RNA molecules with own functionality is very large,» he adds. «I have not designed a molecule that adheres to cancer cells; I have designed a system that can evolve to adhere to cancer cells. »

The entire study has been carried out in vitro, that is, outside of living cells. In 2014, the team of biochemist Floyd Romesberg, at the Scripps Institute in La Jolla, California, succeeded in introducing a six-letter synthetic DNA into a living bacterium. Its molecule was less stable than the hachimoji system, because of the chemical properties