Base-mispairing due to tautomerism to the rare lactim and imino forms The bases of DNA can exist in rare tautomeric forms. The fraction of each type of base in the form of these imino and enol tautomers is about10-4. The imino tautomer of adenine can pair with cytosine, eventually leading to a transition from A-T to G-C; ditto for 5BrU replacing T for T-A to C-G. Spontaneous mutation rate is about 1 in 10 billion / replication / base in E. coli

Deamination of bases: Chemical mutagenesis and possibly carcinogenesis Nitrous acid (HNO2) hydrolyzes amino groups on bases via diazotization. Adenine is deaminated to hypoxanthine, cytosine to uracil, and guanine to xanthine. Hypoxanthine pairs with cytosine, inducing a mutation of A-T to G-C. It is likely that mutations in DNA repair genes will lead to the accumulation of mutations throughout the genome. In time, genes important in controlling cell proliferation become altered, resulting in the onset of cancer. Therefore, beware of nitrite as food preservative, but don’t go to extremes as nitrate is converted to nitrite in our body by gut and oral bacteria.

Nature’s strategy to protect from natural deamination: Use thymine base in DNA Why is a methylated base employed in DNA and not in RNA? Heterocyclic amine hydrolyzes via imine or diazotization. Cytosine in DNA spontaneously deaminates at a perceptible rate to form uracil.

For DNA as codon, this reaction has grave consequence in base pairing For DNA as codon, this reaction has grave consequence in base pairing. With thymine instead of uracil in DNA, U can be recognized and repaired

Steric effect of hexopyranosyl units ("too many atoms") affect base Rationaloe for the ribose-phosphate backbone in nucleic acids 1. Why ribosyl but not glucosyl phosphate as part of duplex chain Steric effect of hexopyranosyl units ("too many atoms") affect base pairing Hexopyranosyl-(4'6') oligonucleotides vs. RNA duplexes

Homo-DNA, an artificial oligonucleotide containing 6-mem Homo-DNA, an artificial oligonucleotide containing 6-mem. pyranose ring with an additional CH2 group, shows much stronger base pairing due to the higher rigidity of pyranose vs. that of furanose rings, resulting in a preorganization of the single strand's backbone conformation toward the double strand's pairing conformation. But the system also has pronounced adenine and guanine self-pairing. For the family of hexopyranosyl-(4'6') oligonucleotides, whose structures differ from that of homo-DNA by 2 additional OH groups and relate to the natural hexoses in the same way that RNA relates to ribose, none exhibit discernible Watson-Crick base pairing between adenine and uracil. Instead, some purine-purine self-pairing occurs, although much weaker than in homo-DNA. Guanine-cytosine pairing is far weaker than in RNA, hence incompetent for informational base pairing. Note: additional OH at 2' equatorial results in a steric clash between this OH and the neighboring nucleobase.

Why are phosphate groups used to form the nucleic acid chain ● A coding tape with polyanions for ionic interactions   Phosphoric acid is specially suited for its role in nucleic acids because it can link two nucleotides and still ionize. The resulting diester is stable to hydrolysis because there is still a negative charge to stabilize it against hydrolysis. The ionic interactions in water serve to retain the molecules within a lipid membrane.

Why not polyamide backbone as illustrated in PNA (Peptide Nucleic Acid) TOO MUCH inter-chain binding (H-bonds and other forces as found in protein secondary structures; also no electrostatic repulsion as present in phosphate anion) negates specific template base-pairing.