From RNA to DNA: Emergence of reverse transcriptases from an ancestral RNA-dependent RNA polymerase

The transition from RNA as the informational molecule of primordial biological systems to the DNA genomes of modern organisms represents one of the greatest evolutionary transitions in the history of life. One way to understand this transition is to comprehend the origin of the enzymes responsible for the metabolism of nucleic acid polymers. In the present work, we reconstructed the ancestral sequence of RNA-dependent DNA polymerase (RdDp) and modeled its structure. The data demonstrate that, in terms of primary sequence, the ancestral sequences exhibit characteristic elements of RdDp; however, structurally, they are more similar to RNA-dependent RNA polymerase (RdRp). The presented data suggest that RdDp may have originated through modifications and neofunctionalization from an RdRp-like ancestor.