Recent papers published in Biosystems and Molecular Biology and Evolution delineated why the RNA world hypothesis does not provide a sufficient foundation for the evolutionary events that followed.
The main objection to the molecule concerns catalysis: Some research has shown that for life to take hold, the mystery polymer would have had to coordinate the rates of chemical reactions that could differ in speed by as much as 20 orders of magnitude. Even if RNA could somehow do this in the prebiotic world, its capabilities as a catalyst would have been adapted to the searing temperatures — around degrees Celsius — that abounded on early Earth.
Before long, the symphony of chemical reactions would have fallen into disarray. Perhaps most importantly, an RNA-only world could not explain the emergence of the genetic code , which nearly all living organisms today use to translate genetic information into proteins. The code takes each of the 64 possible three-nucleotide RNA sequences and maps them to one of the 20 amino acids used to build proteins.
Nature had to find a different route, a better shortcut to the genetic code. It depends on a tight feedback loop — one that would not have developed from RNA alone but instead from a peptide-RNA complex. This implied an elementary kind of coding, a basis for the exchange of information between the RNA and the polypeptide.
He was on his way to sketching what that might have looked like, working backward from the far more sophisticated modern genetic code.
Since then, he, Wills and others have collaborated on a theory that circles back to that research. And so they turned not just to computation but also to genetics. These catalytic enzymes allow RNA to bond with specific amino acids in keeping with the rules of the genetic code. In a recent review , Thomas Cech discussed three RNA worlds, the first being the primordial world before life as we know it, the second consisting of all the current functions of RNA, and the third is the world of custom-designed and engineered RNA molecules, with a host of new functions.
This blog post will examine the first RNA world, with the second and third, hopefully, to be discussed at later times. Early molecular biologists envisioned mostly a DNA and protein world, in which DNA was the store of genetic information, while proteins provided structural support and did all the work. RNA was seen as mostly an intermediary that aided the translation of DNA information into protein sequences.
This neat division started to crack when it was revealed that some viruses use RNA as their genome. David Baltimore and Howard Temin further confused the issue when they showed that RNA could function as a template for the synthesis of DNA through reverse transcriptase.
Things became more complicated still in the s and s when various catalytic functions of RNA were revealed, such as self-splicing RNA transcripts. Francis Crick had suggested in that the early ribosome may have been composed entirely of RNA. Later analysis of modern ribosomes revealed that the peptide bond is formed in the central core without the aid of protein catalysts. Taken together, the evidence seems to suggest that DNA and proteins may be relatively recent inventions of clever RNA molecules.
As we have noted previously [ 5 ], the proposal that the RNA world evolved in acidic conditions [ 5 , 6 ] offers a plausible solution to Charles Kurland's criticism [ 57 ] that the RNA world hypothesis makes no reference to a possible energy source. As de Duve [ 87 ] has noted, "the widespread use of proton-motive force for energy transduction throughout the living world today is explained as a legacy of a highly acidic prebiotic environment and may be viewed as a clue to the existence of such an environment" [ 87 ].
Although Russell, Martin and others [ 23 — 26 ] have argued that proton and thermal gradients between the outflow from hot alkaline pH under-sea hydrothermal vents and the surrounding cooler more acidic ocean may have constituted the first sources of energy at the origin of life, the lack of RNA stability at alkaline pH [ 5 ] and references within would appear to make such vents an unlikely location for RNA world evolution.
Although possible, it seems unlikely that the A-C base pair 'mismatches' found in the tRNA genes of Ferroplasma acidarmanus and Picrophilus torridus two species of archaebacteria with a reportedly acidic internal pH [ 5 ] are corrected by C to U RNA editing that occurs, for example, with some - but not other - plant chloroplast tRNAs [ 88 , 89 ].
Such editing of secondary structure A-C base pair mismatches has so far not been found to occur in archaebacteria; however, in a single archaeal species Methanopyrus kandleri a tertiary structure A-C base pair found in 30 of its 34 tRNAs undergoes C to U editing catalyzed by a cytidine deaminase CDAT8 [ 90 ].
CDAT8, which contains a cytidine deaminase domain and putative RNA-binding domain, has no homologues in other arachaeal species, including F. Definitive proof, however, that the A-C base pairs in these two species are not modified would of course require e. I basically agree with Bernhardt. The RNA World scenario is bad as a scientific hypothesis: it is hardly falsifiable and is extremely difficult to verify due to a great number of holes in the most important parts.
Nevertheless, there is a lot going for the RNA World Bernhardt summarizes much of the evidence, and I add more below whereas the other hypotheses on the origin of life are outright helpless. Moreover, as argued in some detail elsewhere [ 91 ], the RNA World appears to be an outright logical inevitability. To clarify, this does not imply that the primordial RNA World did not have peptides; on the contrary, it is plausible that peptides played important roles but they were not initially encoded in RNA.
Moreover, straightforward observations on modern proteins indicate that the role of RNA in the ancient translation system was much greater that it is in the modern system.
Indeed, Class I aminoacyl-tRNA synthetases aaRS represent only a small branch on the complex evolutionary tree of Rossmann-like domains, so the common ancestor of all 10 Class I aaRS emerged after extensive diversification of this particular class of protein domains had already taken place.
Accordingly, one is compelled to conclude that a high-fidelity translation system that alone would enable extensive protein evolution existed already at the late stages of the hypothetical RNA World [ 92 ].
All this discussion is not pointless play with hypotheses. Realization of the unique status of the RNA World among the origin of life scenarios is critical for maintaining the focus of research on truly important directions such as experimental and theoretical study of the evolution of ribozymes rather than futile attempts to debunk the RNA World. He presents a very open-minded review of recent results and how they impact on old ideas, and distills a large amount of material.
Aside from the admirable attempt to synthesize a vast array of ideas, a valuable contribution hidden within is the critical assessment of the view that the RNA world hypothesis needs to be abandoned in favour of a peptides-first model. While I doubt that anyone seriously excluded peptides as part of a prebiotic milieu, the primacy of peptides does need careful consideration.
In this regard, the explicit explanation of why a pre-genetic code origin of proteins will not be detectable from comparative genomic analyses is an important contribution.
Perhaps this is obvious to some, but in light of a growing view that non-ribosomal peptide synthesis preceded ribosomal peptide synthesis, it would seem that the community needs a reminder, and Bernhardt spells it out in a very informative manner. Another issue with arguing for non-ribosomal peptide synthesis preceding the ribosome is that there is an enormous difference in information input versus output.
Almost always, progress to new understanding is sporadic, with insights coming in separated locales. Difficulties temporarily immobilize discussion, but then are surmounted by a successful theory.
This sometimes inchoate stagger toward a broader, more self-consistent argument is all that can be expected, even of an ultimately successful idea. Discussions of the RNA world sometimes forget this, and demand e. But this essay by Harold Bernhardt remembers what has happened for other successful evolutionary ideas, like the big tree. For all its successes, the tree is still being questioned under extreme prejudice in certain quarters, as is the RNA world.
Contrariwise, here we have here a sympathetic review of the support for the RNA world, which specifically makes the point that it fits our descent better than other ideas You look like the son of a montmorillonite to me, ya mangy mutant! It will be useful to those who want an entry to the RNA world literature, and could easily serve as the crux of a university course. Or to put it in other words, it is edgeless — some attitude would be welcome.
Some choice between hypotheses should go with the territory; some consequent make-or-break predictions are the responsibilities of a guide. But as a gentle introduction, you will not find better. Cold Spring Harb Perspect Biol. Biol Direct. Orig Life Evol Biosph.
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