A group of American scientists created a synthetic molecule of deoxyribonucleic acid, which included four new nitrogenous bases in addition to the four already existing. "Hachimoji" -DNA (eight-letter DNA) is capable of forming a double helix and transcribed into RNA molecules, that is, it can potentially carry genetic information. An article about the study was published in the journal Science.
Experts have synthesized nucleotides ("building blocks" of DNA) P, B, Z and S, which contain nitrogenous bases, similar to purines and pyrimidines in ordinary DNA. Hydrogen bonds are formed between purines and pyrimidines, which are necessary for the formation of the base pairs that make up the double strand of DNA. Thus, S (pyrimidine) binds to B (purine), and P (triazine) binds to Z (pyridine) according to the principle of complementarity, similarly to the way adenine binds to thymine and cytosine to guanine in ordinary four-letter DNA.
It was confirmed that “hachimoji” -DNA meets the basic requirements for ensuring Darwinian evolution, including predictable thermodynamic stability, regardless of the nucleotide sequence. For example, replacing a pair of synthetic bases with another pair will not lead to the loss of crystal properties, that is, mutations can occur in DNA that do not deprive the eight-letter deoxyribonucleic acid of the ability to carry genetic information and, in theory, to transmit it by inheritance.
Scientists also managed to transcribe "hachimoji" -DNA, that is, to use it as a template for the synthesis of hachimoji-RNA molecules. First, the researchers tested the necessary enzyme for this - RNA polymerase, isolated from the bacteriophage T7 virus and capable of selecting each nucleotide in the DNA strand corresponding to the complementarity principle of ribonucleotide ("building blocks" of RNA).
It turned out that this type of polymerase is not capable of attaching only ribonucleotide S, corresponding to nucleotide B, to the growing chain of hachimoji RNA. To solve this problem, the researchers sorted out several mutant polymerase variants and found that one of them - FAL polymerase with three amino acid substitutions - is capable of working with all four new "letters". This allowed the researchers to construct a fluorescent Spinach aptamer from Hachimoji RNA, a short molecule capable of binding to the DFHBI molecule, causing it to emit green light.
According to scientists, the creation of eight-letter DNA may be useful in various areas of synthetic biology, and also expands the understanding of possible biological structures in alien life.
