Theoretical origin of life: RNA lab manufactured (Introduction)

by David Turell , Thursday, March 18, 2021, 20:49 (1128 days ago) @ David Turell

Knowing what is required in an RNA world, this lab Frankensteined together a better mousetrap all by intelligent design:

https://science.sciencemag.org/content/371/6535/1225?utm_campaign=toc_sci-mag_2021-03-1...

"The RNA World Hypothesis posits that at the dawn of evolution, RNA played a key role in the establishment of life. Central to this hypothesis is the existence of an RNA replicase ribozyme capable of copying its own genome using a supply of prebiotically synthesized nucleotide monomers and RNA polymers. Ever since the class I ligase ribozyme was isolated from a high-diversity RNA pool, there has been a sustained effort to produce highly processive polymerase ribozymes. Because the affinity of these polymerases for their RNA templates is weak, with Michaelis constant (KM) values in the millimolar range, the most successful strategies to date have colocalized polymerase ribozymes with their substrates using concentration-enhancing micelles or by anchoring either the RNA template or the RNA primer to be extended to the polymerase ribozyme. These strategies create a high local concentration of primer template with respect to the polymerase but fail to create a truly processive polymerase by virtue of the tethering strategies used to enhance polymerization.

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"All extant DdRPs, including the bacteriophage polymerases, use a variation of this two-step process. Thus, we selected a ribozyme with a similar mechanism to explore the potential connection between promoter recognition and processivity.

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"We engineered three changes into this parental ribozyme by appending a PBS to its 5′ end, synthesizing a high-diversity pool containing 1013 sequence variants by inserting random sequence libraries at three distinct sites, and removing sequence from the B6.61 accessory domain known to be redundant.

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After 25 rounds of selection, a substantial decrease in pool diversity occurred, with the final five rounds of selection being dominated by five major ribozyme polymerase families.

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"Through in vitro evolution, we have found an RNA polymerase that can search for a promoter by first forming a functional open holopolymerase complex and then in a second step rearrange into a processive elongation form. The correct assembly of this CPCLOSED complex results in a more than one order of magnitude increase in extension, with extension on randomly generated templates being directly comparable to the best RNA polymerase ribozymes isolated to date, which on highly repetitive tethered templates are able to synthesize 75 to 203 nt of sequence."

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Although many outstanding challenges remain to producing a self-evolving system in the laboratory, including increased polymerization rate, fidelity, and, most importantly, strand displacement, the development of a promoter-dependent RNA polymerase ribozyme with processive clamping ability offers many insights into the dilemmas faced by life in the earliest periods of evolution on this planet. (my bold)

Comment: I have necessarily omitted all the intricate details of how they cobbled this molecule together. The color red segment in the bold shows what they really proved. It takes intelligent design.