We have often considered the difficulties inherent in the popular RNA world scenario that is envisioned for primitive life. According to this model, prior to the emergence of DNA and proteins, RNA ribozymes served as the first replicators. The model is intended to circumvent the problem of causal circularity — that DNA must be copied by proteins, which are themselves coded for by DNA. Problems abound for the RNA world theory. Chief among those are the inherent instability of RNA (being single stranded, and possessing an additional 2’ OH group, rendering it prone to hydrolysis) and the fact that ribozymes have not been shown to be capable of complete self-replication. 

A Physical Limitation

Indeed, on this latter point, when RNA forms complementary base pairs to fold back on itself, part of the molecule no longer presents an exposed strand that can serve as a template for copying. Thus, there is a physical limitation on the capability of RNA to self-replicate.

Another problem that has not received as much attention is the problem of replication fidelity. What do I mean by this? An important requirement of life is a means of minimally accurate self-replication. Biologist Jack Szostak explains that “In order for RNA to have emerged as the genetic polymer that enabled protocells to evolve in a Darwinian manner, the process of RNA replication must have been accurate enough to allow for the transmission of useful information from generation to generation, indefinitely.”¹ Indeed, as biochemist Sy Garte observes, when the replication fidelity falls below a certain threshold, “modern organisms undergo an error catastrophe from which they cannot recover, as has been shown in the cases of viruses, aging, in evolution and in macromolecular replication in early life.”² Viruses, particularly RNA viruses, are close to this critical threshold, with approximately one mutation per replication — and, in fact, increasing the rate of mutations to result in an error catastrophe has been proposed as an anti-viral strategy.^3,4,5

A Minimum for Life?

What is the minimum level of replication fidelity needed to sustain life? This “has been estimated to be equal to 1-(1/L), where L is the length of the information molecule polymer.”⁶ The size of the smallest ribozymes is in the ballpark of around 50 ribonucleotides.⁷ For a string of ribonucleotides of this length, Jack Szostak concludes that “the error rate during template copying should be less than ~2% at each position, assuming that only about half of the nucleotide positions need to be specified, but each position must be copied twice for full replication.”⁸ But what is the average error rate during RNA copying? According to one study, this was estimated to be around 17 percent, which is significantly higher than the error rate threshold given above.⁹ With optimized nucleotide ratios, however, this may be reduced to less than 10 percent. And (since U residues are the biggest contributors to error rate, resulting from G:U mismatch formation) it may be even further decreased to around 5 percent on GC-rich templates.¹⁰ This, however, suggests a finely tuned and optimized sequence of ribonucleotides. And, yet, 5 percent is still too high — more than double what it needs to be for survival and evolution. Thus, Szostak concludes, “Clearly, a robust means of further reducing the error rate is critical if non-enzymatic RNA replication is to serve as the means for initiating Darwinian evolutionary processes.”¹¹ Again, though, this will require additional levels of fine-tuning and design.

“A Sort of Phase Transition”

Sy Garte, in a paper published in BioCosmos, invites us to consider that the minimum threshold of replication fidelity needed to sustain life “represents a sort of phase transition” — values below this threshold cannot be increased by evolutionary mechanisms.¹² This presents a significant challenge to naturalistic origin-of-life scenarios, since natural selection is impotent to produce the high replication fidelity needed for life to thrive and for evolution itself to take place. The earliest life must therefore have had a minimally reliable replication system right from the beginning. This is extremely difficult to account for on the hypothesis of naturalistic evolution. This fact, however, becomes much less surprising on a design-based view, since intelligent agents can optimize and fine-tune engineered systems.

Garte concludes his paper by noting, 

While the concept of emergence is a useful phenomenological description of what happens at phase transitions, it is quite likely that further progress into elucidating the emergence of biology from chemistry might require the use of radically new perspectives on possible biological mechanisms, including teleology, which are beyond the scope of this report.

On a Design-Based View

Thus, Garte expresses an openness to teleological explanations with regard to the origin of life. How might such a teleological inference be expressed? As a Bayesian, I conceive of evidence in terms of a likelihood ratio — the probability of the evidence given the hypothesis (on the numerator) against the probability of the evidence given the falsity of the hypothesis (on the denominator). The top-heaviness of this likelihood ratio (referred to as the Bayes factor) corresponds to the evidential value of the observation under consideration. On a design-based view, it is not particularly surprising that the first life would be finely optimized to reduce copying errors sufficiently for survival and evolution. On the other hand, it is really quite surprising on the falsity of the design hypothesis. Thus, this data tends to confirm a design-based framework.

Notes

1. Szostak, J.W. The eightfold path to non-enzymatic RNA replication. J Syst Chem. 2012 3(2).
2. Garte S. Evidence for Phase Transitions in Replication Fidelity and Survival Probability at the Origin of Life. BioCosmos. 2021 1(1):2-10.
3. Bull JJ, Sanjuán R, Wilke CO. Theory of lethal mutagenesis for viruses. J Virol. 2007 Mar;81(6):2930-9.
4. Anderson JP, Daifuku R, Loeb LA. Viral error catastrophe by mutagenic nucleosides. Annu Rev Microbiol. 2004;58:183-205.
5. Eigen M. Error catastrophe and antiviral strategy. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13374-6.
6. Garte S. Evidence for Phase Transitions in Replication Fidelity and Survival Probability at the Origin of Life. BioCosmos. 2021 1(1):2-10.
7. Ferré-D’Amaré AR, Scott WG. Small self-cleaving ribozymes. Cold Spring Harb Perspect Biol. 2010 Oct;2(10):a003574.
8. Szostak, J.W. The eightfold path to non-enzymatic RNA replication. J Syst Chem. 2012 3(2).
9. Leu K, Obermayer B, Rajamani S, Gerland U, Chen IA. The prebiotic evolutionary advantage of transferring genetic information from RNA to DNA. Nucleic Acids Res. 2011 Oct;39(18):8135-47.
10. Szostak, J.W. The eightfold path to non-enzymatic RNA replication. J Syst Chem. 2012 3(2).
11. Ibid.
12. Garte S. Evidence for Phase Transitions in Replication Fidelity and Survival Probability at the Origin of Life. BioCosmos. 2021 1(1):2-10.