RNA World Update

Conversation
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Indeed, also the fact that the PTC (and rRNA in general) is produced in a manner that relies on DNA as the template, that doesn’t imply that DNA was always the template for rRNA. We already know that DNA isn’t the only thing that can serve as a template for RNA. RNA can be a template for itself. As pointed out before, non-reverse transcribing RNA viruses (Baltimore groups III, IV, and V) do this all the time. The RNA strands of their genomes act both as mRNAs to make viral proteins, such as RdRps, AND these strands also act as templates for said RdRps. Although in the case of group V (-ssRNA viruses) the mRNA has to be transcribed from the single stranded genome first.

Furthermore, we also know that these genes can go from being RNA-templated to DNA-templated. Sometimes, a random reverse-transcription enzyme may encounter the genome of a non-RT RNA virus and reverse transcribe it into DNA, which can be integrated in to the DNA genome of the host, becoming a ‘nonretroviral integrated RNA viruse’ (NIRV). Of course, ERVs are a lot more common since reverse-transcription is a part of the retrovirus life cycle, but NIRVs do happen.

So, RNA can act as templates for RNA, and act as mRNA for protein, and act as catalysts (ribozymes), and they can transition into the ‘DNA world’ via reverse-transcription. I agree that these facts alone are not nearly enough to solve the origin of life; how the biosphere operated prior to DNA, and how/why the transition to DNA happened. However, it does show that the hypothesis cannot be dismissed simply by pointing out that… currently

Furthermore…

Not always. Sometimes the introns are able to fold into a structure which catalyzes their own splicing. For example, Group I and II introns (The spliceosome likely evolved from these). The nobel prize winning discovery by Cech’s lab in 1981 (previously alluded to by @Rumraket) of a pre-rRNA that was able to splice out an intron even in the absence of proteins was among the first experimental demonstrations of ribozymes.

First a nitpick: post-transcription modifications into non-canonical bases mostly occurs prior to the separation of the rRNAs.

More importantly, we also know of base-modifying ribozymes.

[Not a specific response to @theaz101, just some commentary for anyone here] Related to these base-modifications, a paper from a couple of years ago discusses these non-canonical bases (in tRNA) and argues that they are vestiges for an RNA-peptide world. Another curious note, the manner at which rRNA is modified are quite different between domains of life. While Archaeans and Eukaryotes mostly rely on small-RNA guided ribonucleoproteins (sRNPs/snoRNPs), these are absent in bacteria which solely rely on site-specific enzymes. Yet, a significant portion of these modifications are shared, by type and location in tRNA and rRNA, across the domains of life. Very reminiscent of what @Rumraket mentioned about the fact that the enzymes of DNA replication is not conserved between eukaryotes/archaeans and bacteria. To me this implies that the non-canonical bases in rRNA and tRNA are more ancient than the enzymes that makes them from canonical bases, which makes sense if they are indeed relics of the RNA(-peptide) world. Perhaps prebiotic chemistry provided more than just the four canonical (Watson-Crick) base pairs, and the precursors to tRNA and rRNA were also composed of non-canonical bases as well. If this is the case, I suspect that some of non-canonical bases would’ve ended up functionally embedded and ‘locked-in’ the modern structures. Even after the four canonical bases came to dominate inside nucleic acids (perhaps because ATGC have the most stable and least error-prone base pairing [see here]), these non-canonical bases are still required, but now they have to be produced from the canonical 4 via processes that evolved independently in Bacteria and Archaea [at least, that’s my impression]. Also came accross this review paper published very recently, but it’s paywalled :frowning:.

Well, one can make a good argument that all life STILL is “RNA based”, and that DNA is just a version of RNA that is modified to be chemically inert (hence why DNA is not very catalytic).

Quoting a relevant section from one of my favorite books on the subject:
NOTE: The authors make a distinction between ‘weak’ and ‘strong’ RNA world. They accept the minimal premises of the ‘weak’ version, but they contest the additional premises of the ‘strong’ version (a.k.a. RNA-first), e.g. that RNAs were able to undergo template-replication and that their Darwinian evolution led to biochemistry, in contrast to the continuity with geochemistry that is emphasized by metabolism-first proponents. I tend to agree with their assessments.

From “The Origin and Nature of Life on Earth The Emergence of the Fourth Geosphere” by Eric Smith and Harold J Morowitz

Page 347 [Emphasis mine]

Weak RNA World: The minimal set of assumptions defining the RNA World, we will term the conservative RNA World, or weak RNA World. They are: (1) that life passed through a stage in which proteins did not yet exist to carry the function of catalysis, and DNA did not carry the function of heredity; and (2) that in this stage both of these functions were carried by RNA.{6} The weak RNA World may describe much of cellular life before the advent of the ribosome as a translation apparatus from RNA to proteins. The relatively conservative interpretation of an RNA World is as well motivated as any proposal for early life, and only becomes stronger and more appealing as our understanding of RNA expands. Today it would not be an exaggeration to describe the cell as an RNA-regulated machine in which a very narrow set of functions has been transferred to DNA,{7} and a less narrow but still restricted set of functions has been taken on by peptides.{8} RNA has retained functions in small-molecule catalysis, interference-based regulation, and to a limited extent, large-molecule catalysis [203]. Had the RNA World concept arisen today rather than against a history of cell biology in which RNA had been regarded largely as a “helper molecule,” we might refer to the modern era still as an “RNA World,”{9} and to the pre-DNA and pre-translation era simply as less differentiated stages in the complex systems biology of RNA.

  1. Examples of assumptions that are not implied in a conservative interpretation include:

    1. That peptides were absent or that they were not functional; the only assumption is that they were not produced by translation and thus were not genetically encoded catalysts;
    2. that copying of RNA was carried out in an RNA-only system, or that the preservation of RNA reflected competition in the rates of copying;
    3. above all, that RNA replication was the first process to distinguish geochemistry from life, or that Darwinian competition among RNA replicators was a necessary prerequisite to the formation of metabolism.

  2. DNA is the “queenbee” of the cell, specialized for preserving and transmitting hereditary information but atrophied in most other functions possessed by RNA.

  3. These include not only catalysis, but also structure, traction and trafficking, and all-important, the regulation of gene expression itself.

  4. This richer understanding of the roles of RNA is captured by Cech in his reference to a “second RNA World” of the present [122].

Some more that go in deeper discussions about rRNA. Interestingly, they hypothesize that the ribosome was basically the first genome; the template for its own replication and a mRNA for making ribosomal proteins.

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A post was merged into an existing topic: Is there really information being conveyed within a cell?

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I moved @Nesslig20 's comment to create a new topic because I felt it deserved more attention than it was likely to get buried deep in another discussion. Use the link below to see the replied-to comment in the original context.

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True, but you both seem to be missing the fact that the nature of PT was predicted before it was known. That makes it significant evidence, regardless of anyone’s post hoc thinking about it.

This is another empirical fact that is routinely concealed by the IDcreationists whose hearsay @theaz101 is basing his opinions on.

So one has to ask, if this isn’t convincing evidence, why conceal it from @theaz101? This is not obscure stuff, as both findings won Nobels.

And yet again, @theaz101’s hypothesis has made another false empirical, perfectly objective prediction (presented as fact).

The most important point.

Other questions:

  1. Why is translation initiated by a tRNA, but terminated by proteins?
  2. Why have tRNAs at all, when it’s trivial to evolve proteins that bind specific DNA sequences in the lab?
  3. While all proteins are synthesized beginning with methionine, what proportion of functional proteins retain it?

All of these questions are addressed by the RNA World hypothesis. IDcreationists can’t even muster a design explanation after the fact.

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And that, is pretty darn cool. :slight_smile:

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I thought sure that the “RNA World Update” would be the Universal Studios official press release announcing a new theme park in Orlando, Florida.

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I should clarify that #3 is explained not by the RNAW hypothesis itself, but by evolution after proteins get involved in translation.

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Last month, there was a very nice Perspective article in Nature Chemistry on the RNA World as an “intellectual framework” for theorizing about the OOL. Sadly it’s paywalled but you can read it here without downloading. I put some excerpts below and am happy to send the PDF on request.

Intellectual frameworks to understand complex biochemical systems at the origin of life

Abstract:

Understanding the emergence of complex biochemical systems, such as protein translation, is a great challenge. Although synthetic approaches can provide insight into the potential early stages of life, they do not address the equally important question of why the complex systems of life would have evolved. In particular, the intricacies of the mechanisms governing the transfer of information from nucleic acid sequences to proteins make it difficult to imagine how coded protein synthesis could have emerged from a prebiotic soup. Here we discuss the use of intellectual frameworks in studying the emergence of life. We discuss how one such framework, namely the RNA world theory, has spurred research, and provide an overview of its limitations. We suggest that the emergence of coded protein synthesis could be broken into experimentally tractable problems by treating it as a molecular bricolage—a complex system integrating many different parts, each of which originally evolved for uses unrelated to its modern function—to promote a concrete understanding of its origin.

End of introduction:

In this Perspective, we examine how the RNA world framework spurred research, and where it may reach its limitations when addressing the emergence of complex systems. We introduce Jacob’s molecular bricolage (Box 1) as a possible intellectual framework through which to study the early complexification of life.

Beginning of first section, “Intellectual frameworks as a guide,” with nice historical overview (emphasis mine):

Notably, the RNA world theory created a concrete intellectual framework with which to explore a possible origin of life. The RNA world theory itself was originally sparked by the newly determined structure of transfer RNA (tRNA)—the molecule that physically links specific RNA information (anticodons, which bind to messenger RNA (mRNA)) to particular amino acids. The structure of tRNA exhibited unexpected complexity compared with the double helix of DNA, including multiple stems and loops and stacking of secondary structure elements to give an overall L-shaped structure. The complexity in RNA folding was reminiscent of the protein folding seen in enzymes. Since sequence information determines structure, which determines function, this observation led to speculation that perhaps the complexity of the structure adopted by RNA indicates that RNA, too, could have complex functions such as catalysis. The proof that RNA could indeed catalyse reactions came decades later in the 1980s, in the laboratories of Sidney Altman and Thomas Cech, who shared the Nobel Prize in Chemistry in 1989 for the discovery of catalytic RNA, or ribozymes, in biology. Notably, both laureates devoted substantial time in their Nobel lectures to the topic of the origin of life. In retrospect, the discovery of catalytic RNA initiated sustained excitement about the RNA world theory as a conceptual lens through which experimentalists could probe the origin of life.

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For me, that seems inadequate as I don’t see that anyone has a good idea as to which came first: metabolism (moving protons across barriers) or RNAs. The RNA World hypothesis (still short of theory status IMO) still works for either, as it simply means that RNA came before protein.

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Regarding metabolism first ideas, I have also seen people emphasizing electrons and organic chemistry, such as the following often quoted phrases:

"The purpose of life is to hydrogenate carbon dioxide”
Michael Russell

“Life is nothing but an electron looking for a place to rest”
Albert Szent-Györgyi

Let’s consider the biochemistry of the smallest compounds with the fewest carbon atoms, particularly the rTCA (reductive citric acid cycle) and closely associated organic molecules. They have peculiar properties, such as being ‘sticky’ for CO2 and the network itself is structured such that it is self-amplifying. AND… every material found in the whole biosphere is synthezised from biochemcial pathways which start from one of the compounds of this small network. It’s like the center of a web, reminiscent of the phrase “all-roads-lead-to-rome” because all roads were build from that city.

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These properties seem very law-like such that (even I would make a bet that) a biochemical network like this should be at the core of the biochemistry that sustains any other biosphere in the whole universe. Sorry, but no silicon-based life. A good short article written by authors of the book I referenced previously.

Yes, the authors (Eric Smith and Harold Morowitz) make a distinction between the ‘weak’ and ‘strong’ RNA worlds.

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I normally like to make the distinction between metabolism first vs RNA first hypotheses for the origin of life. But speaking of the RNA world more broadly, the term encompasses the whole range of models from those that say RNA came before DNA, to those that posit life basically began with some sort of self-replicating system of RNA molecules. And there’s a lot of different versions in between.

I am definitely persuaded there was some sort of RNA world preceding DNA-based life, where the primary genetic material was RNA and many of the roles today performed by proteins were also done by RNA. I am much less persuaded by the idea that life began basically “directly” with the prebiotic synthesis of RNA, and that a sort of self-replicating system emerged for the first time when a collection of RNA molecules learned to replicate.
While I am sure scientists will eventually discover that such a system is possible (I do believe RNA sequence space contains the much searched for self-replicase that can fully replicate itself, and that they will find it rather soon, they are already close), I nevertheless think the geochemical scenarios conjectured to give rise to it seem too ad-hoc and rather contrived.

I think some sort of metabolism (or even a messy chemistry) preceded RNA, and that evolution began in this chemical system before the emergence of the first genetic polymers (which RNA is likely to have been), and that RNA was quite possibly a kind of parasite similar to a virus, that eventually integrated itself with the host and like some transposons, eventually gained functions that served the host, and ended up taking over the whole system.

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@Nesslig20 I have restored the topic. It was “Deleted by Automatic Timer”, which is a housekeeping function of Discourse, but I don’t know why yet.

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A brilliant and detailed new review article is up at a respected online journal. It provides some clear new insights into the RNA World and a provocative prediction.*

*In the rollover text

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