All extant DNA- and protein-based life may have descended from RNA-based life on the early Earth in which an RNA polymerase ribozyme catalyzed the replication of RNA genomes and the synthesis of ribozymes, including itself. Aiming to recreate these long-extinct activities in the laboratory, a directed in vitro evolution procedure has been developed to select RNA polymerase ribozymes able to synthesize functional RNA aptamers or ribozymes from RNA templates. Evolved variants of the class I polymerase ribozyme are now able to synthesize a variety of complex, structured RNAs and replicate short RNA sequences in an RNA-catalyzed form of the polymerase chain reaction. More recently, the polymerase has been shown to synthesize large parts of itself, including a functional form of the ancestral ligase that composes its catalytic core. A fragmented form of the polymerase can spontaneously assemble into a functional ribozyme that can in turn synthesize many of its constituent fragments, suggesting that it may be possible for a polymerase to construct itself from mononucleotides. Serendipitously, evolutionary improvement of RNA polymerase activity has also expanded catalytic promiscuity, retaining significant activity when the newly synthesized or templating strands contain nucleic acids with deoxyribose (DNA), threose (TNA), or arabinose (ANA) backbones. The details of the transition from RNA-based genetic systems to DNA-based ones remains unknown, while TNA and ANA-based genetic systems have been proposed as precursors or contemporaries to RNA-based life. The ability of an RNA polymerase to promiscuously catalyze information transfer between these distinct nucleic-acid-like molecules suggests a relatively shallow barrier to evolutionary transitions between early genetic systems. Most notably, the emergence without selection of forward and reverse transcriptase activity suggests that RNA polymerase ribozymes could have transferred RNA-based genetic information to and from DNA, enabling the evolution of DNA genomes prior to the invention of genetically-encoded proteins.

RNA-catalyzed polymerization of RNA, DNA, TNA, and ANA

2019 Fall National Meeting

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