DNA is made up of nucleobases represented by the letters A, T, G and C. They form the basis of the genetic code and are present in all living things. But in a bacteriophage, another base, represented by the letter Z, exists. This exception, the only one observed to date, has long remained a mystery. Scientists from the Institut Pasteur and the CNRS, in collaboration with the CEA, have now elucidated the biosynthetic pathway of this database. This work was published in the April 30, 2021 issue of Science.
DNA, or deoxyribonucleic acid, is a molecule that acts as a carrier for storing genetic information in all living organisms. It is a double helix characterized by an alternation of purine nucleobases (adenine and guanine) and pyrimidinucleobases (cytidine and deoxycytidine). The bases of each DNA strand are located in the center of the helix and are linked together, thus connecting the two DNA strands: adenine forms two hydrogen bonds with thymine (AT) and guanine forms three bonds. hydrogen with cytosine (GC). This applies to all living things, with one exception.
Cyanophage S-2L, an exception to conventional genetics
Cyanophage S-2L is a bacteriophage, that is, a virus that infects bacteria. In this phage, adenine is completely replaced by another base, 2-aminoadenine (represented by the letter Z). The latter forms three hydrogen bonds with thymine (ZT), instead of the usual two bonds between adenine and thymine. This higher number of bonds increases the stability of DNA at high temperatures and changes its conformation, which means that DNA is less well recognized by proteins and small molecules.
2-aminoadenine biosynthetic pathway elucidated
Since its discovery in 1977, the S-2L cyanophage has been the only known exception, and the 2-aminoadenine biosynthetic pathway has remained unknown. Scientists from the Institut Pasteur and the CNRS, in collaboration with the CEA, recently elucidated this biosynthetic pathway and demonstrated its enzymatic origins. They did this by identifying a homolog of the known enzyme succinoadenylate synthase (PurA) in the cyanophage S-2L genome. A phylogenetic analysis of this family of enzymes revealed a link between the homolog, known as PurZ, and the enzyme PurA in archaea. This indicates that the homolog is an ancient enzyme which likely conferred an evolutionary advantage. The research was carried out using the crystallography platform of the Institut Pasteur.
The new ZT base pair and the discovery of the biosynthetic pathway show that new bases can be incorporated enzymatically into genetic material. This increases the number of coding bases in DNA, paving the way for the development of synthetic genetic biopolymers.
Source of the story:
Material provided by Pastor Institute. Note: Content can be changed for style and length.