Theoretical origin of life; flaws of RNA-World theory (Introduction)

by David Turell , Saturday, February 15, 2020, 15:09 (1531 days ago) @ David Turell

thoughts from a chemist:

https://www.chemistryworld.com/opinion/flaws-in-the-rna-world/4011172.article

"The hypothesis of an ‘RNA world’ as the font of all life on Earth has been with us now for more than 30 years, the term having been coined by the biologist Wally Gilbert in 1986. You could be forgiven for thinking that it pretty much solves the conundrum of how the replication of DNA could have avoided a chicken-and-egg impasse: DNA replication requires protein enzymes, but proteins must be encoded in DNA. The intermediary RNA breaks that cycle of dependence because it can both encode genetic information and act catalytically like enzymes. Catalytic RNAs, known as ribozymes, play several roles in cells.

"It’s an alluring picture – catalytic RNAs appear by chance on the early Earth as molecular replicators that gradually evolve into complex molecules capable of encoding proteins, metabolic systems and ultimately DNA. But it’s almost certainly wrong. For even an RNA-based replication process needs energy: it can’t shelve metabolism until later. And although relatively simple self-copying ribozymes have been made,1 they typically work only if provided with just the right oligonucleotide components to work on. What’s more, sustained cycles of replication and proliferation require special conditions to ensure that RNA templates can be separated from copies made on them.

"Perhaps the biggest problem is that self-replicating ribozymes are highly complex molecules that seem very unlikely to have randomly polymerised in a prebiotic soup. And the argument that they might have been delivered by molecular evolution merely puts the cart before the horse....It’s nigh impossible to see how anything lifelike could come from it without mechanisms for both concentrating and segregating prebiotic molecules – to give RNA-making ribozymes any hope of copying themselves rather than just churning out junk, for example.

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"Joyce and his coworkers have now found a ribozyme that holds the potential to copy heritable ‘pre-genetic’ information into RNAs considerably more complex and structured than any seen before.

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"The best RNA polymerase the researchers obtained this way had a roughly 8% chance of inserting any nucleotide wrongly, and any such error increased the chance that the full chain encoded by the molecule would not be replicated. What’s more, making the original class I ligase was even more error-prone and inefficient – there was a 17% chance of an error on each nucleotide addition, plus a small chance of a spurious extra nucleotide being added at each position.

"These errors would be critical to the prospects of molecular evolution, since there is a threshold error rate above which a replicating molecule loses any Darwinian advantage over the rest of the population – in other words, evolution depends on good enough replication. Fidelity of copying could thus be a problem, hitherto insufficiently recognised, for the appearance of a self-sustaining, evolving RNA-based system: that is, for an RNA world.

"Maybe this obstacle could have been overcome in time. But my hunch is that any prebiotic molecule will have been too inefficient, inaccurate, dilute and noise-ridden to have cleared the hurdle. Rather, we’ll need to look for ways in which noisy, heterogeneous and perhaps compartmentalised molecular collectives could have bootstrapped their way to life. And that, after all, makes complete sense when you recognise that this is precisely what cells still are."

Comment: As Paul Davies noted in his book, a miracle is needed. All the lab work is intelligent design.