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Transitioning to DNA Genomes in an RNA World

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Transitioning to DNA Genomes in an RNA World INSIGHT ORIGIN OF LIFE Transitioning to DNA genomes in an RNA world The unexpected ability of an RNA polymerase ribozyme to copy RNA into DNA has ramifications for understanding how DNA genomes evolved. RAZVAN COJOCARU AND PETER J UNRAU In modern metabolism, protein-based Related research article Samanta B, Joyce enzymes called reverse transcriptases can copy GF. 2017. A reverse transcriptase ribozyme. RNA to produce molecules of complementary eLife 6:e31153. DOI: 10.7554/eLife.31153 DNA. Other enzymes can promote the produc- tion of DNA nucleotides (the building blocks of DNA molecules) from RNA nucleotides via chal- lenging chemical reactions. So how did the first DNA genomes come to be? There are two pos- or as long as history has been recorded, sibilities within the framework of the RNA world. humanity has tried to answer the ancient In the first, protein enzymes evolved before question of our origins. The ‘central DNA genomes. In the second, the RNA world F contained RNA polymerase ribozymes that were dogma’ of molecular biology, first stated by Fran- able to produce single-stranded complementary cis Crick in 1958, represented a major step for- DNA and then convert it into stable double- ward in our efforts to answer this question stranded DNA genomes. (Figure 1A; Crick, 1958). In this model, the A number of laboratories around the world genetic information stored in DNA is transcribed are trying to build ribozymes that can sustain to produce RNA, which is then translated by the RNA replication (Wang et al., 2011; ribosome to produce chains of amino acids. Attwater et al., 2013). Recently, David Horning These chains fold to make the proteins that are and Gerald Joyce artificially evolved a ribozyme responsible for almost everything that happens in that is capable of copying complex RNAs and cells. amplifying short RNA templates (Horning and The flow of information from DNA to RNA to Joyce, 2016). Now, in eLife, Joyce and Biswajit protein is thought to have evolved out of a simpler Samanta at the Salk Institute demonstrate that evolutionary period when genetic information this ribozyme is also a reverse transcriptase was stored and transmitted solely by RNA mole- (Samanta and Joyce, 2017). Feeding DNA cules. This theory, known as the ‘RNA world nucleotides to this ribozyme enabled it to copy hypothesis’, posits that an RNA enzyme or ‘ribo- short segments of RNA templates into comple- zyme’ capable of copying RNA molecules existed mentary DNA. This suggests that if an RNA early in evolution, and that protein synthesis by world contained DNA nucleotides, DNA Copyright Cojocaru and Unrau. the ribosome (which is also an RNA enzyme) genomes could have been assembled and then This article is distributed under the evolved out of this system (Figure 1B; Gil- presumably replicated by ribozymes. terms of the Creative Commons Whether DNA genomes existed very early in Attribution License, which permits bert, 1986; Atkins et al., 2011). The theory, how- evolution fundamentally rests on whether DNA unrestricted use and redistribution ever, is largely silent on how DNA genomes provided that the original author and evolved. nucleotides were available in the RNA world. source are credited. There are plausible routes by which RNA and Cojocaru and Unrau. eLife 2017;6:e32330. DOI: https://doi.org/10.7554/eLife.32330 1 of 3 Insight Origin of life Transitioning to DNA genomes in an RNA world A Replication dNTPs dNTPs DNA RT Protein RNA Protein Transcription Translation NTPs B Replication NTPs dNTPs dNTPs RdRp DNA RT Ribozyme RNA Figure 1. The emergence of DNA genomes in the RNA world. (A) In the central dogma of molecular biology, information flows from DNA (red oval) to RNA (green oval) to protein (blue box). DNA is formed of building blocks called deoxynucleoside triphosphates (dNTPs) and can be replicated (solid looping red arrow); RNA is formed of nucleoside triphosphates (NTPs). Enzymes called reverse transcriptases (RT) enable complementary DNA to be made from the building blocks of RNA (dashed arrow). Blue rectangles represent processes catalyzed by proteins; green rectangles show processes catalyzed by RNA; translation is mediated by an RNA catalyst (green inner rectangle) that has proteins that modulate its activity (blue outline). (B) In the RNA world, ribozymes (RdRp) replicate RNA genomes (solid looping red arrow). Based on the work of Joyce and Samanta, if dNTPs were present in the RNA world, reverse transcriptase ribozymes could have constructed DNA genomes using RNA genomes as a template (straight red arrow). Ribozymes could also have potentially replicated DNA genomes (dashed red arrow). DNA nucleotides could have been synthesized also available early in evolution, then the synthe- before life emerged, meaning that they are likely sis of DNA nucleotides by an RNA system to have been available at the dawn of an RNA appears likely. While this area is currently under- world (Ritson and Sutherland, explored experimentally, there appears to be no 2014; Becker et al., 2016; Kim and Benner, fundamental reason why DNA nucleotides could 2017). Likewise, artificially selected ribozymes not have been abundant quite early in evolution. have been used to synthesize the two types of Demonstrating that DNA polymerase ribo- bases found in RNA nucleotides from simpler zymes are able to rapidly use such DNA nucleo- precursors, suggesting RNA nucleotides could tides would represent a major step forward for have been built by early RNA systems the early DNA genome model. While the field of (Martin et al., 2015). If DNA precursors were artificial RNA polymerase ribozymes has made Cojocaru and Unrau. eLife 2017;6:e32330. DOI: https://doi.org/10.7554/eLife.32330 2 of 3 Insight Origin of life Transitioning to DNA genomes in an RNA world rapid strides, their ability to add multiple nucleo- Chemistry 5:1011–1018. DOI: https://doi.org/10.1038/ tides rapidly is still very limited. Current ribo- nchem.1781, PMID: 24256864 zymes are significantly longer and more complex Becker S, Thoma I, Deutsch A, Gehrke T, Mayer P, Zipse H, Carell T. 2016. A high-yielding, strictly than the sequences that they are able to copy, regioselective prebiotic purine nucleoside formation but to make self-evolving systems, ribozymes pathway. Science 352:833–836. DOI: https://doi.org/ need to be able to copy sequences that are lon- 10.1126/science.aad2808, PMID: 27174989 ger and more complex than themselves. It will Crick FH. 1958. On protein synthesis. Symposia of the Society for Experimental Biology 12:138–163. therefore be exciting to see if the techniques PMID: 13580867 that have created such RNA polymerases are Gilbert W. 1986. Origin of life: The RNA world. Nature also able to evolve DNA polymerase ribozymes 319:618. DOI: https://doi.org/10.1038/319618a0 that have the potential to make self-replicating Horning DP, Joyce GF. 2016. Amplification of RNA by systems using DNA and not RNA as a source of an RNA polymerase ribozyme. PNAS 113:9786–9791. genetic material. Such a system would bring us DOI: https://doi.org/10.1073/pnas.1610103113, PMID: 27528667 closer to understanding the transition from an Kim HJ, Benner SA. 2017. Prebiotic stereoselective RNA world to a type of life that respects the synthesis of purine and noncanonical pyrimidine rules of the central dogma of modern biology. nucleotide from nucleobases and phosphorylated carbohydrates. PNAS 114:11315–11320. DOI: https:// doi.org/10.1073/pnas.1710778114, PMID: 29073050 Razvan Cojocaru is in the Department of Molecular Martin LL, Unrau PJ, Mu¨ ller UF. 2015. RNA synthesis Biology and Biochemistry, Simon Fraser University, by in vitro selected ribozymes for recreating an RNA Burnaby, Canada world. Life 5:247–268. DOI: https://doi.org/10.3390/ Peter J Unrau is in the Department of Molecular life5010247, PMID: 25610978 Biology and Biochemistry, Simon Fraser University, Ritson DJ, Sutherland JD. 2014. Conversion of biosynthetic precursors of RNA to those of DNA by Burnaby, Canada photoredox chemistry. Journal of Molecular Evolution [email protected] 78:245–250. DOI: https://doi.org/10.1007/s00239-014- https://orcid.org/0000-0003-1392-6948 9617-0, PMID: 24736972 Competing interests: The authors declare that no Samanta B, Joyce GF. 2017. A reverse transcriptase competing interests exist. ribozyme. eLife 6:e31153. DOI: https://doi.org/10. 7554/eLife.31153, PMID: 28949294 Published 01 November 2017 Wang QS, Cheng LK, Unrau PJ. 2011. Characterization of the B6.61 polymerase ribozyme accessory domain. References RNA 17:469–477. DOI: https://doi.org/10.1261/rna. Atkins JF, Gesteland RF, Cech TR. 2011. RNA Worlds. 2495011, PMID: 21224380 Cold Spring Harbor Laboratory. Attwater J, Wochner A, Holliger P. 2013. In-ice evolution of RNA polymerase ribozyme activity. Nature Cojocaru and Unrau. eLife 2017;6:e32330. DOI: https://doi.org/10.7554/eLife.32330 3 of 3.
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