Chapter 2: The Earth, Life and Genomic Uracil

Life emerged some 3.8 billion years ago, possibly even earlier. Furthermore, in the scenarios for non-enzymatic synthesis of molecules still present in all life forms, uracil was among those found in substantial yields. Uracil may thus have been one of the original bases in RNA polymers in the hypothetical prebiotic RNA World. It may also have been one of the bases in the first cells, which were thought to contain RNA as the hereditary material. The transition to a DNA World had major advantages; the DNA backbone is much more stable than that of RNA because of the reactivity of 2′-hydroxyl group in ribose. This allowed expansion of DNA-genome sizes. Furthermore, RNA replication is intrinsically error-prone compared to DNA replication. DNA cells appear to have completely outcompeted RNA cells. If RNA cells still exist, they must be confined to hitherto unexplored niches. RNA viruses may be remnants of RNA cells, although their origin remains uncertain. The transition from RNA to DNA cells was made possible by evolution of ribonucleotide reductase (RNR, Chapter 3.1.3). This enzyme converts ribonucleotides to deoxyribonucleotides, the building blocks of DNA. The first DNA cells probably contained uracil in the genome, since RNR could directly produce dATP, dGTP, dCTP and dUTP from the corresponding ribonucleotides, but not dTTP. Furthermore, DNAviruses carrying uracil instead of thymine in their genomes do exist, possibly representing relics of a uracil-DNA world…