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Challenge to Origin of Life: Replication (with References)

Long Story Short, Episode 8 View at YouTube

What is life and how did it originate? Many origin of life researchers claim that life started as a primitive self-replicating molecule, and evolved from there into all the complex forms of life we observe. But does the evidence support this? This video reviews obstacles to forming a self-replicating system, challenging the “RNA World” and “RNA-Peptide World” hypotheses and other supposed examples of self-replicating molecules.

This is the fifth of several episodes about the origin of life presented as part of the Long Story Short series. More episodes here.

References and Notes

Sources and notes from the video.

  1. Note: Replicating DNA is a very complex process. This paper shows that it takes a minimum of 14 different enzymes (made of 25 proteins) to replicate DNA. Su’etsugu, M.; Takada, H.; Katayama, T.; Tsujimoto, H. “Exponential propagation of large circular DNA by reconstitution of a chromosome-replication cycle“, Nucleic Acids Research 2017, 45 (20), 11525-11534.
  2. Note: The name was coined by Walter Gilbert later, in 1986.
  3. Lincoln, T. A.; Joyce, G. F. “Self-sustained replication of an RNA enzyme“, Science 2009, 323 (5918), 1229-1232.
  4. Adamala, K.; Engelhart, A. E.; Szostak, J. W. “Generation of functional RNAs from inactive oligonucleotide complexes by non-enzymatic primer extension“, Journal of the American Chemical Society 2015, 137 (1), 483-489.
  5. Robertson, M. P.; Joyce, G. F. “Highly efficient self-replicating RNA enzymes“, Chemistry & Biology 2014, 21 (2), 238-245.
  6. Mizuuchi, R.; Furubayashi, T.; Ichihashi, N. “Evolutionary transition from a single RNA replicator to a multiple replicator network, Nature Communications 2022, 13 (1), 1-10.
  7. Vaidya, N.; Manapat, M. L.; Chen, I. A.; Xulvi-Brunet, R.; Hayden, E. J.; Lehman, N. Spontaneous network formation among cooperative RNA replicators, Nature 2012, 491 (7422), 72-77.
  8. Jeancolas, C.; Matsubara, Y. J.; Vybornyi, M.; Lambert, C. N.; Blokhuis, A.; Alline, T.; Griffiths, A. D.; Ameta, S.; Krishna, S.; Nghe, P. “RNA diversification by a self-reproducing ribozyme revealed by deep sequencing and kinetic modelling“, Chemical Communications 2021, 57 (61), 7517-7520.
  9. (accessed December 2022).
  10. (accessed December 2022).
  11. Mills, D. R.; Peterson, R.; Spiegelman, S. “An extracellular Darwinian experiment with a self-duplicating nucleic acid molecule“, Proceedings of the National Academy of Sciences 1967, 58 (1), 217-224.
  12. Joyce, G. F. “Forty years of in vitro evolution“, Angewandte Chemie International Edition 2007, 46 (34), 6420-6436.
  13. Note: This isn’t some inherently unique capacity of RNA, as it is often assumed. Because life uses RNA both to carry information (such as mRNA during protein synthesis) and for enzymatic activity, there is an impression that RNA is some special case of an object that can both perform physical functions and store information. However, any physical object with at least 2 conformational states can serve as an information storage device (including sticks and stones). Therefore, practically any object that performs a physical function can also be used to store information. The reverse is also true, and there is evidence that the cell’s main information storage medium, DNA, could also perform certain enzymatic functions, although that is not how DNA is currently used in life.
  14. Note: “If ribozyme-catalysed metabolic reactions exist at all, they account for only a marginal fraction of cellular metabolism.”. Ralser, M. “An appeal to magic? The discovery of a non-enzymatic metabolism and its role in the origins of life“, Biochemical Journal 2018, 475 (16), 2577-2592. Benner, S. A.; Burgstaller, P.; Battersby, T. R.; Jurczyk, S. “Did the RNA world exploit an expanded genetic alphabet? Cold Spring Harbor Monograph Series 1999, 37, 163-182. Wilson, T. J.; Lilley, “D. M. RNA catalysis — is that it?“, RNA 2015, 21 (4), 534-537. DOI: 10.1261/rna.049874.115  From NLM.
  15. Note: Stealing, really? Yes, they are taking things they ought not. That’s stealing.
  16. Deck, C.; Jauker, M.; Richert, C. Efficient enzyme-free copying of all four nucleobases templated by immobilized RNA, Nature Chemistry 2011, 3 (8), 603-608. Adamala, K.; Szostak, J. W. “Nonenzymatic template-directed RNA synthesis inside model protocells“, Science 2013, 342 (6162), 1098-1100.
  17. Szostak, J. W. “The eightfold path to non-enzymatic RNA replication“, Journal of Systems Chemistry 2012, 3 (1), 1-14.
  18. Engelhart, A. E.; Powner, M. W.; Szostak, J. W. Functional RNAs exhibit tolerance for non-heritable 2′–5′ versus 3′–5′ backbone heterogeneity, Nature Chemistry 2013, 5 (5), 390-394.
  19. Note: Engelhart, Powner, and Szostak took a relatively simple ribozyme that could break bonds.  The correct linkage (3′-5′) made a ribozyme that could break 80% of bonds in 48 hrs (Figure 3b).  Then they tried a ribozyme with 10% of the wrong linkage (2′-5′). That one could break 60% of bonds in 48 hours.  With 25% of the wrong linkage, it broke about 25% of the bonds in 48 hours. With 50% of the wrong linkage, it broke only a few % of the bonds in 48 hours.
  20. Note: A second major problem with the chemical replication of RNA is that RNA duplexes greater than 20– 30 nucleotides in length are difficult or impossible to thermally denature under template copying conditions” Engelhart, A., Powner, M. & Szostak, J. “Functional RNAs exhibit tolerance for non-heritable 2′–5′ versus 3′–5′ backbone heterogeneity“.
  21. Eigen, M. “Selforganization of matter and the evolution of biological macromolecules“, Naturwissenschaften 1971, 58 (10), 465-523.
  22. Note: Ref#7 Above.  Quote “To create a cooperative network, we fragmented the Azoarcus ribozyme into two pieces in three different ways with the intent of observing how they could spontaneously reassemble via intermolecular cooperation (Fig. 1a, b). We manipulated the IGS (canonically GUG) and its target triplet to generate both matched and mismatched partners.”.
  23. Note: Ref#8 above.  Quote: “First, we show that RNA1 is elongated by multiple additions of small fragments in the presence of the ribozyme.”.
  24. Note: Ref#6 above.  Quote: “Long-term evolution of an RNA replicator. The RNA replication system (Fig. 1a) consists of a single-stranded RNA (host RNA) that encodes the catalytic subunit of Qβ replicase (an RNA-dependent RNA polymerase) and a reconstituted Escherichia coli”.
  25. Di Giulio, M. On the RNA world: evidence in favor of an early ribonucleopeptide world. Journal of molecular evolution 1997, 45 (6), 571-578. Piette, B. M.; Heddle, J. G. A peptide–nucleic acid replicator origin for life, Trends in Ecology & Evolution 2020, 35 (5), 397-406. Müller, F.; Escobar, L.; Xu, F.; Węgrzyn, E.; Nainytė, M.; Amatov, T.; Chan, C. Y.; Pichler, A.; Carell, T. “A prebiotically plausible scenario of an RNA–peptide world“, Nature 2022, 605 (7909), 279-284.
  26. Bernhardt, H. S. The RNA world hypothesis: the worst theory of the early evolution of life (except for all the others)a, Biology Direct 2012, 7 (1), 1-10.
  27. Note: Something like Le Chatelier’s Principle — where, if a chemical reaction would have happened naturally, increasing the concentration of those chemicals would speed it up. For instance if nature could produce a chemical and make a reaction happen over the course of 100 years, we could artificially increase the concentration to decrease the time needed for that same reaction to happen. Assuming, of course, that the reactants have very long shelf-lives and the reaction could occur at all with such a low concentration. Frequently the concentrations of available reactants use in the putative origin of life conditions were so low as to not allow the desired reactions to happen at all. So even this could be cheating if the reaction is not merely sped up, but enabled to happen when it otherwise wouldn’t.
  28. Jia, T. Z.; Fahrenbach, A. C.; Kamat, N. P.; Adamala, K. P.; Szostak, J. W. “Oligoarginine peptides slow strand annealing and assist non-enzymatic RNA replication“, Nature Chemistry 2016, 8 (10), 915-921.
  29. Jia, T. Z.; Fahrenbach, A. C.; Kamat, N. P.; Adamala, K. P.; Szostak, J. W. Retraction Note: “Oligoarginine peptides slow strand annealing and assist non-enzymatic RNA replication“, Nature Chemistry 2017, 9 (12), 1286-1286.
  30. Note: Though some believe DNA arose simultaneously with RNA, which has its own problems beyond the scope of this video.