The Interplay between RNA and DNA Modifications: Back to the RNA World
Patrick Forterre and Henri Grosjean
An RNA/protein world (probably cellular) is widely accepted as a probable step in the early evolution of life. During subsequent life evolution various enzymes emerged that allowed some organisms to generate deoxyribonucleotides from ribonucleotide precursors and to synthesize DNA molecules using ancestral RNA genomes as templates. Later on, once the DNA became the major repository of genetic information, cells and viruses had to develop new strategies to protect their DNA genomes against the aggressive chemical environment and/or destructive enzymes produced by competitors. This was performed mainly by further modifying the DNA genomes after their synthesis through pre and postreplicative enzymatic processes, using enzymes, mostly methyltransferases and deaminases that were probably initially designated to modify primordial RNAs. Relics of this ancient interplay between RNA and DNA modification in cells and viruses are still abundant in our modern \'DNA‑makes‑RNA‑makes‑proteins\' world. Some enzymes are still able today to modify both DNA and RNA, demonstrating the versatility of the modification apparatus and testifying for the time when proteins of the late RNA world were recruited to work with DNA. Here, we review what is known about these enzymes that were designated to synthesize DNA within the framework of a hypothetical cellular and viral co‑evolution. From this analysis, DNA appears as just another type of (hyper)modified RNA polymer, specialized in storing the genetic inheritance of the living organisms.