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make3 a day ago

read up on the RNA world theory, it's so cool

HarHarVeryFunny 21 hours ago | parent | next [-]

Have you seen this MLST interview of Blaise Aguera ?

https://www.youtube.com/watch?v=rMSEqJ_4EBk

He's an interesting person overall - the long interview is well worth watching if you haven't already seen it - but the relevance here are his experiments with the emergence of self-replicating computer programs out of random components.

His starting point is entire "programs" (random sequences of 64 characters, of which only ~7 have any meaning - the program "statements" of the BF language), so perhaps more suggestive of this RNA world stage, but perhaps also of what came before it when there may have been collectively self-replicating soups consisting of discrete components rather then entire structural encodings.

adrian_b 19 hours ago | parent | prev [-]

Parts of the RNA world theory are correct, but other parts are completely bogus and completely illogical.

What is correct is that RNA must have existed a very long time before DNA, during which RNA was the only nucleic acid.

Moreover, self-replicating RNA must have existed before ribosomes and proteins (where "protein" means a polypeptide that is synthesized using a RNA template).

It should be obvious that neither ribosomes nor protein-encoding RNA-sequences may exist before the existence of self-replicating RNA, because the living being in which those would exist would immediately die without descendants, together with its content of ribosomes and proteins.

So far so good, but some of the supporters of the RNA World theory claim that before the existence of protein-based enzymes, all chemical reactions inside a living being must have been catalyzed by RNA molecules.

This is an illogical claim, which is false beyond any reasonable doubt. Some RNA-based catalysts may have existed quite early, and some still exist today. However, any RNA-based catalyst could have appeared only at a later time after the establishment of RNA self-replication. The argument is the same as for protein-based catalysts, any living being with a RNA catalyst, but without RNA replication would die and the RNA catalyst would disappear without descendants.

So there is no doubt that the first feature of RNA that has appeared was self-replication, and at that time RNA could not have any other role inside a living being, because any such role would not have been inherited.

In other words, the first self-replicating RNA molecules were a kind of RNA virus, which multiplied inside the existing living beings, consuming energy and substances, without providing benefits. Only later, when eventually RNA templates have become the main method for synthesizing the useful components of a living being, something akin to a symbiosis between RNA and the rest of the living being was achieved, arriving to the structure of life that is known today.

For the first self-replicating RNA molecule to appear, the living beings must have contained abundant ATP and the other nucleotides. So the original role of the nucleobases in living beings was not the storage of information, but the storage of the energy required for synthesizing organic polymers. The self-polimerization of the nucleotides, which forms RNA, was an unwanted side reaction. In other words, before the RNA world, there already was an ATP world, which was the first user of nucleobases.

If RNA could not have been the material for making enzymes before the proteins, such enzymes must have been made from peptides (i.e. polymers of amino-acids), exactly like the enzymes of today, but those peptides must have not been synthesized using ribosomes, like the proteins. Such peptides still exist today and they remain widespread in all living beings, and they are named non-ribosomal peptides. Their mechanisms of synthesis are much less understood than the mechanisms of RNA-based protein synthesis. It is likely that more research into non-ribosomal peptides might provide a better understanding of how a living being without RNA could function.

In order to have a self-replicating living being you do not need a self-replicating molecule able to store arbitrary information, like RNA. It is enough to have a chain of synthesis reactions that closes a positive-feedback cycle, i.e. the products of one reaction are reactants for the next reaction and the products of the last reaction are the reactants for the first. If the chain of reactions produces all the components of a living being, growth and self-replication can be achieved.

The defect of such a living being is that evolution is extremely difficult. any mutation in one of the catalysts used in the chain of reactions is more likely to break the positive feedback and lead to death, instead of producing an improved living being. After the appearance of memory molecules, i.e. RNA and later DNA, which can store the recipe for making an arbitrary polymer molecule, it became possible to explore by mutations a much greater space of solutions, leading to a greatly accelerated evolution of the living beings.

gus_massa 14 hours ago | parent | next [-]

I read a few times your comment and I went from "Nah" to "It makes a lot of sense". I'm adding the "ATP word" to my list of interesting ideas.

Some related stuff:

* https://www.science.org/doi/10.1126/science.adt2760 They made RNA that copies itself, but it use as a starting point activated triplets of bases. i.e, if ATP is AR-PPP, they use a mix of something compounds like AR-P-AR-P-AR-PPP that stil have the triphosphate to store energy and be easy to link, but already have tree linked bases. This is even more difficult that a soup of ATP and friends.

* https://en.wikipedia.org/wiki/PAH_world_hypothesis The idea is that before the RNA word, there was something simpler, like this. Is it possible to use ATP to build more PAH? I also remember about a version of RNA that instead of ribose it used something smaller (glicerol?), but I can't find it.

asdff 7 hours ago | parent | prev | next [-]

>However, any RNA-based catalyst could have appeared only at a later time after the establishment of RNA self-replication.

RNA by virtue of its biochemistry is capable of self replication already. Sequence affinity alone is sufficient to drive structure formation. But without a template, structure can also form on its own (example of an open access paper exploring one such mechanism under certain conditions, 1).

This would be enough to kick start things.

1. https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002...

adrian_b 4 hours ago | parent [-]

Nope.

RNA is not capable of self replication. RNA by virtue of its biochemistry is only capable to be used as a template for replication, but the copying of the template must be done by a different molecular machinery.

If you put almost any RNA molecule in a jar together with monomers, you can wait until the end of time to see its replication.

Normally, RNA can be replicated only by a special enzyme, a RNA-dependent RNA polymerase. This kind of protein is used by many viruses.

It is hypothesized that a RNA molecule with a very special structure might have been used in the beginning as the catalyst for template-controlled polymerization, instead of a RNA-dependent RNA polymerase, to ensure self-replication. Some experiments have suggested that this is indeed possible.

Only after a self-replicating RNA molecule already existed, or if a RNA molecule existed in combination with a RNA polymerase that was produced by other means than by using a RNA template, other RNA molecules with various other functions could appear, and they would have been replicated by the already existing mechanisms, so they would be inherited by the descendants of a living being.

The link provided by you has nothing to do with RNA replication.

It describes a mechanism for the polymerization of nucleotides, which produces random nucleic acid molecules, not molecules that replicate an existing template.

A chemical reaction of this kind is what must have existed before the appearance of a self-replicating RNA molecule. Among the many random polymers produced before that, there was eventually one capable of self-replication, which started the evolution of genetic information.

This kind of reaction is what I have referred to as "side reactions" that happened during the use of ATP and of the other nucleotides as energy sources for the polycondensation reactions used in living beings to make macromolecules.

XorNot an hour ago | parent | next [-]

> RNA is not capable of self replication. RNA by virtue of its biochemistry is only capable to be used as a template for replication

RNA molecules which can synthesize others have been produced in a lab.[1,2] Your claim is not only totally unsupported, it's been experimentally disproven.

Laboratory RNA production can be done with regular batch chemistry - no enzymes involved, so on a long enough time span heat and mixing would be able to polymerase candidates out of the primordial soup.

RNA self-affinity is well documented, double-stranded RNA viruses exist[2] so stable conformational arrangements of RNA are not only experimentally proven but so viable they exist in todays much more enzymatically hostile world.

The relative difficulty of the structure persisting is a point in favor it is as a replication medium, since if RNA could tightly bind RNA then templating new strands would inactivate it.

[1] https://www.science.org/doi/10.1126/science.1060786

[2] https://www.pnas.org/doi/full/10.1073/pnas.1610103113

[3] https://en.wikipedia.org/wiki/Double-stranded_RNA

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