Natural selection of specific protobiomonomers during abiogenic development of the prototype genetic code is hindered by the diversity of structural, spatial, and rotational isomers that have identical elemental composition and molecular mass (M), but can vary significantly in their physicochemical characteristics, such as the melting temperature Tm, the Tm:M ratio, and the solubility in water, due to different positions of atoms in the molecule. These parameters differ between cis- and trans-isomers of dicarboxylic acids, spatial monosaccharide isomers, and structural isomers of (...) α-, β-, and γ-amino acids. The stable planar heterocyclic molecules of the major nucleobases comprise four (C, H, N, O) or three (C, H, N) elements and contain a single –C=C bond and two nitrogen atoms in each heterocycle involved in C–N and C=N bonds. They exist as isomeric resonance hybrids of single and double bonds and as a mixture of tautomer forms due to the presence of –C=O and/or –NH2 side groups. They are thermostable, insoluble in water, and exhibit solid-state stability, which is of central importance for DNA molecules as carriers of genetic information. In M–Tm diagrams, proteinogenic amino acids and the corresponding codons are distributed fairly regularly relative to the distinct clusters of purine and pyrimidine bases, reflecting the correspondence between codons and amino acids that was established in different periods of genetic code development. The body of data on the evolution of the genetic code system indicates that the elemental composition and molecular structure of protobiomonomers, and their M, Tm, photostability, and aqueous solubility determined their selection in the emergence of the standard genetic code. (shrink)

Properties of non‐canonical GC base pairs and their relations with mechanochemical cleavage of DNA are analyzed. A hypothesis of the involvement of the transient GC wobble base pairs both in the mechanisms of the mechanochemical cleavage of DNA and epigenetic mechanisms involving of 5‐methylcytosine, is proposed. The hypothesis explains the increase in the frequency of the breaks of the sugar‐phosphate backbone of DNA after cytosines, the asymmetric character of these breaks, and an increase in break frequency in CpG after cytosine (...) methylation. As an alternative hypothesis, probable implication of GC+ Hoogsteen base pairs is considered, which now exemplify the best‐studied non‐canonical GC base pairs in the DNA double helix. Also see the video abstract here https://youtu.be/EUunVWL0ptw. (shrink)