Comment by adrian_b

Comment by adrian_b 2 days ago

13 replies

About a half of the amino acids used in proteins, i.e. ten of them, can form easily in abiotic conditions and they are widespread in some celestial bodies.

They are easily distinguished from terrestrial contaminants, because they are a mixture of left-handed and right-handed isomers.

When analyzing the genetic code in order to determine which amino acids have already been used in the earlier versions of the genetic code and which have been added more recently, the same simpler amino acids that are easy to synthesize even in the absence of life are also those that appear to have been the only amino acids used earlier.

The article contains the phrase "Given the fact that the current scenario is that life on Earth started with RNA".

This is a fact that it is too often repeated like if it were true, when in reality one of the few things that can be said with certainty about the origin of life is that it has not started with RNA.

What must be true is only that RNA had existed a very long time before DNA and DNA has been an innovation that has been the result of a long evolution of already existing life forms, long before the last ancestor of all living beings that still exist now on Earth.

On the other hand, proteins, or more correctly said peptides, must have existed before any RNA. Moreover, ATP must have existed long before any RNA.

RNA has two main functions based on its information-storage property: the replication of RNA using a template of RNA (which was the single form of nucleic acid replication before the existence of DNA) and the synthesis of proteins using RNA as a template.

Both processes require complex molecular machines, so it is impossible for both of them to have appeared simultaneously. One process must have appeared before the other and there can be no doubt that the replication of RNA must have appeared before the synthesis of proteins.

Had synthesis of proteins appeared first, it would have been instantly lost at the death of the host living being, because the RNA able to be used as a template for proteins could not have been replicated, therefore it could not have been transmitted to descendants.

So in the beginning RNA must have been only a molecule with the ability of self replication. All its other functions have evolved in living beings where abundant RNA existed, being produced by self replication.

The RNA replication process requires energy and monomers, in the form of ATP together with the other 3 phosphorylated nucleotides. Therefore all 4 nucleotides and their phosphorylated forms like ATP must have existed before RNA.

ATP must have been used long before RNA, like today, as a means of extracting water from organic molecules, causing the condensations of monomers like amino acids into polymers like peptides.

The chemical reactions in the early living forms were certainly regulated much less well than in the present living beings, so many secondary undesirable reactions must have happened concurrently with the useful chemical reactions.

So the existence of abundant ATP and other phosphorylated nucleotides must have had as a consequence the initially undesirable polymerization and co-polymerization of the nucleotides, forming random RNA molecules, until by chance a self-replicating RNA molecule was produced.

Because the first self-replicating RNA molecule did not perform any useful function for the host life form, but it diverted useful nucleotides from its metabolism, this first self-replicating RNA molecule must be considered as the first virus. Only much later, after these early viruses have evolved the ability to synthesize proteins, some of them must have become integrated with their hosts, becoming their genome.

The catalytic functions that are now performed mostly by proteins, i.e. amino acid polymers that are synthesized using an RNA template, must have been performed earlier by peptides, i.e. typically shorter amino acid polymers that are synthesized without the use of RNA templates.

Even today, all living beings contain many non-ribosomal peptides, which are made without RNA, using processes that are much less understood than those that involve nucleic acids.

The difference between a living being that would be able to make only non-ribosomal peptides and one that makes proteins using RNA templates is pretty much the same difference as between a CPU with hard-wired control and a CPU with micro-programmed control, with the same advantages and disadvantages.

Life forms able to reproduce themselves must have existed before the appearance of the nucleic acids, but they must have been incapable of significant evolution, because any random change in the structure of the molecules that composed them would have been very likely to result in a defective organism that would have died without descendants. This is similar with a hard-wired control, where small random changes in the circuits are unlikely to result in a functional device.

On the other hand, once the structure of the enzymes was written in molecules of nucleic acids, the random copying errors could result in structures very different from the original structures, which could not have been obtained by gradual changes in the original structures without passing through non functional structures that could not have been inherited.

So the use of molecules that can store the structural information of a living being has enabled the evolution towards much more complex life forms, but it cannot have had any role in the apparition of the first life forms, because the replication of any such molecule requires energy that can be provided only by an already existing life form.

tim333 2 days ago

>On the other hand, proteins, or more correctly said peptides, must have existed before any RNA

How come? It seems you can have reproducing RNA without protein needed. Here's Gerald Joyce talking briefly about making those https://youtu.be/aBrYsFeeVzE?t=171

  • adrian_b a day ago

    Reproducing RNA without proteins has nothing to do with the necessity of peptides/proteins existing before any RNA.

    Polymerizing nucleotides into RNA requires energy and monomers that can be provided only by an already living being with a functional metabolism.

    That requires enzymes for catalyzing the chemical reactions that compose the metabolism, which must have been non-ribosomal peptides, before the existence of nucleic acids.

    The main source of energy for the first life forms must have been the conversion of free hydrogen (dihydrogen) and carbon monoxide and/or dioxide into acetic acid (acetogenesis). An auxiliary source of energy could have been the gradient of ions that exists in hydrothermal vents. Both sources of energy have their origin in the oxidation of volcanic rocks by water, and the energy comes ultimately from the internal heat of the planet (because the volcanic rocks formed at high temperatures, where they are in chemical equilibrium, are no longer in chemical equilibrium in the presence of water after they cool to lower temperatures). At least for now, there is no known mechanism for the appearance of life elsewhere than on a planet with water, internal heat and volcanism.

    Some people see that simple organic substances can form in any place in the cosmic space where there is not enough oxygen to oxidize them, so they assume that perhaps life could appear there. However that is wrong, because without a continuous source of energy all those organic substances will stay dead forever. The only suitable continuous source of energy is the internal heat of big enough planets, which will not cool quickly, because capturing the energy of stellar light requires very complex structures that cannot be generated spontaneously, but they can be only the result of a long evolution of already existing life forms.

    • 0u89e a day ago

      >>>Some people see that simple organic substances can form in any place in the cosmic space where there is not enough oxygen to oxidize them, so they assume that perhaps life could appear there.

      LUCA is considered anaerobic - any contact with oxygen would have killed it. However we do not know what were preRNA Life forms.

      >>>However that is wrong, because without a continuous source of energy all those organic substances will stay dead forever.

      Unless they are getting frozen and put on pause, like all the stable chemical ingredients can exist in your household.

      >>>The only suitable continuous source of energy is the internal heat of big enough planets, which will not cool quickly, because capturing the energy of stellar light requires very complex structures that cannot be generated spontaneously, but they can be only the result of a long evolution of already existing life forms.

      The only known life, that is known to me that can process stellar light are plants and animals, that have eaten plants and are getting sugar from their cells, that are integrated into their organism.

      I am not sure what this text was compiled together from, but most of chemical processes that are happening on any planet does not require any stellar light. Initially all of matter was part of a Sun and when it went Supernova, it involved some stellar light, but after that, no need for that.

      >>>The main source of energy for the first life forms must have been the conversion of free hydrogen (dihydrogen) and carbon monoxide and/or dioxide into acetic acid (acetogenesis). An auxiliary source of energy could have been the gradient of ions that exists in hydrothermal vents. Both sources of energy have their origin in the oxidation of volcanic rocks by water, and the energy comes ultimately from the internal heat of the planet (because the volcanic rocks formed at high temperatures, where they are in chemical equilibrium, are no longer in chemical equilibrium in the presence of water after they cool to lower temperatures). At least for now, there is no known mechanism for the appearance of life elsewhere than on a planet with water, internal heat and volcanism.

      This also looks like something compiled from different thoughts. But, ok - in terms of Life originating on the planet, this is only more or less applicable to evolutionary stage of Life, that happened on our planet in thermal vents, and only when planet was stable enough for a Life to exist there as we have no idea if Life was on our planet already, before Theia merged into our planet and destroyed everything organic, which seems to have been the case. But the issue here is not so much if Life originated on our planet, but where all the previous organic forms evolved, which are considered much older than our planet and primordal soup that is needed to create Life simply could not have happened in thermal vent like you are supposing.

      From what I have read, comets are excellent places for primordal soup to happen as one of the prerequisites for a Life. Whenever they are approaching Sun, there is water boiling and all the processes that are similar to what thermal vents would have, but with light in addition and plentiful of resources for Life to spring. Like I mentioned earlier, freezing over would not reverse chemical processes that ere happening during that boiling and in next approach they would continue and there is basically indefinite time for those cycles to happen and disperse whatever end products that were happening on comets whenever they were passing plants - not to mention if they would land on them. There is life, that can exist in atmosphere, so there is actually no need for a comet to hit a planet to disperse product from their primordial soup. So, generally comets are one of the stages for prereq of Life, where explosion of Suns to disperse their thermonuclear product is previous stage. There seems to be impossible for Life not to appear the way how Universe functions.

      PS I am not challenging RNA stuff, but Life also includes preRNA Life, so while your POV in regards to RNA based Life seems to be ok, everything outside of those boundaries are not ok.

highfrequency 2 days ago

Awesome post and thanks for writing this out - probably the most insightful piece I’ve read on plausible origin of life through pre-RNA autocatalytic peptides. Would you be willing to share a contact email / online profile? (could edit afterward to delete if you are worried about spam from crawlers)

sdwr 2 days ago

Beautiful work! Do you have any thoughts on the relative size of complexity spaces explored by different forms of mutation?

exe34 2 days ago

sorry if I missed it, but it sounds like you've just pushed the mystery one step back but still ended up with the same mystery - where did the original Titan species come from? is there any evidence for their existence other than your belief that an RNA replicator would have needed a host cell? would this host cell have been built out of lipid bilayers? what would its inside mechanisms be made of - if not protein or RNA?

  • nathan_compton 2 days ago

    Ultimately science always terminates in so-called brute facts. I'm not sure it always makes sense to call these mysteries. In the end, some things appear to simply be without any sort of causal or even logical explanation. I try not to get too worked up about it.

    On the other hand, one has to keep kicking over rocks to see what is underneath or life would get boring.

  • adrian_b a day ago

    It is not certain that the first living beings consisted of cells. This is actually very unlikely.

    The very first living being that was able to reproduce itself could not have had a closed cell membrane, because that cannot function without pores and pumps provided by peptides/proteins, which control the exchange of substances through the membrane.

    The very first self-reproducing chemical system is likely to have been an open structure formed by organic substances attached to the surface of a mineral containing the catalysts for the metabolic reactions, e.g. an iron sulfide impurified with nickel and cobalt.

    There is a hypothesis, which seems very plausible, that before the appearance of closed cells, the living beings consisted of discoidal fatty membranes with peptides attached to them, which obstructed pores in minerals located in hydrothermal vents, where the environment provided a flux of ions equivalent with the flux of ions that must be provided by ionic pumps in any closed living cell.

    It is likely that only after the development of active trans-membrane ionic pumps, it became possible for living beings to take the form of free closed cells, unattached to minerals.

    It is not clear which happened first, the transition to free closed cells or the apparition of self-replicating RNA.

    The first membranes must have also been formed by molecules with hydrophobic and hydrophilic parts like the present lipid bilayers. However the molecules must have been different and simpler. Perhaps the first membranes were made just of free fatty acids, but with short chains. They certainly must have been much more permeable than today, to allow the passing of some molecules for which there were not yet adequate transporters. In any case, the phospholipids that are dominant today in membranes are likely to have appeared only some time later than the first life forms.

    There is not much positive evidence about the early forms of life, but there is a lot of evidence about many things that are impossible, so we can say for sure that they could not have existed in the first forms of life.

    We can say with absolute certainly that no other function of RNA could have existed before it acquired the ability of self-replication. More precisely, if any such function would have happened accidentally in any living being it would have been immediately lost forever, because it could not have been transmitted to descendants.

    We can also say with absolute certainty that the self-replication of RNA could never appear otherwise than in an environment where a source of energy ensured a continuous production of the 4 monomers required for making RNA.

    That environment must have been an already existing living being, not only because there is no other known environment that could produce phosphorylated nucleotides, but also because without such an already living host there would not have been a path of evolution for the self-replicating RNA, where it acquired extra abilities of catalyzing other chemical reactions, culminating in the ability of synthesizing proteins, such that eventually the mechanism of making proteins via RNA has substituted in most cases the mechanisms for making non-ribosomal peptides.

    There are many other things that we know that they could not have existed in the first living beings. Most of the living beings that we know, including many anaerobic bacteria from places without light about which it is frequent to see in the popular but incompetent press claims that they live independently of the Sun, depend either directly or indirectly on the phototrophic living beings, which capture solar energy.

    There are only two kinds of bacteria or archaea that are really independent of the solar energy, which do either acetogenesis or methanogenesis. We can rule out with certainty both phototrophy and methanogenesis as sources of energy for the first living beings, which leaves only acetogenesis, a process for which there is ample evidence that it already existed in the ancestor of all present living beings.

    Besides the source of energy, we also have a pretty good knowledge about the chemical composition of the first living beings.

    While a human needs around 20 chemical elements, much less are needed for the simplest self-reproducible life forms.

    5 non-metals are certainly needed in any life form for the organic substances: H, C, N, O and S. These happen to also be the most abundant non-metals in the Universe (not counting noble gases). The minimal set of metabolic reactions for a self-reproducing chemical system powered by acetogenesis requires at least 3 catalytic metals, iron, nickel and cobalt. The consumption of carbon dioxide instead of the less abundant carbon monoxide and of dinitrogen instead of the less abundant ammonia requires an additional catalytic metal, either molybdenum or tungsten. This extra catalyst may be a later addition to the living beings, enabling them to also live in less reducing environments, where carbon monoxide and ammonia became scarce. Besides organic substances and catalysts, there is a necessity for the first living beings to have abundant potassium ions in their environment, in order to neutralize the excess of organic acids from living matter. While in the present oceans sodium is more abundant, forcing all living beings to have means to expel sodium from their cells, it is likely that in the early oceans potassium was more abundant because it is easier dissolved from the volcanic rocks than any other component, so it was the first to become abundant in sea water, until the concentration of other ions has caught up with it after the passing of time has brought them in solution too.

    This brings the total to 9 chemical elements that are certain to have been used in the first self-replicating living beings. With the later increase in complexity, other chemical elements must have been added, the most important being the addition of phoshphorus (as phosphoric acid) and of magnesium, which have lead to the use of ATP as a dehydrating agent, presumably replacing the earlier use of thioesters, which had as a byproduct the appearance of RNA.

    There are a lot of unknowns, but there are also a lot of restrictions to the space of possible solutions, so there are chances that eventually it would become possible to demonstrate a self-replicating system of chemical reactions that could be similar with the first forms of life, even if it is unlikely that the solution is unique, so we might never know the precise details how it happened.

    • nerdralph 18 hours ago

      What about sulfur-reducing bacteria? The process also requires iron, but seems to be possible without cobalt (desulfovibrio africanus).

kjkjadksj 17 hours ago

> RNA has two main functions based on its information-storage property: the replication of RNA using a template of RNA (which was the single form of nucleic acid replication before the existence of DNA) and the synthesis of proteins using RNA as a template.

This heavily simplifies what RNA is capable of doing. When we talk about the ribosome templating rna to make protein, that is true, but the ribosome itself is made out of structural rRNA and some rna bound protein. RNAs have been found to have enzyme activity alone. When people talk about the RNA world hypothesis they mean that RNA is sufficient to be the information and catalytic unit of early life, as a sort of occams razor what is the most simple step with the fewest parts involved before taking more complicated steps with more separate pieces sort of way.

“ the majority of known ribozymes carry out mostly phosphoryl transfer reactions”

Now that sure seems like a potential smoking gun for an early phosphorylation based energy cycle.

https://pmc.ncbi.nlm.nih.gov/articles/PMC10583251/

f1shy 2 days ago

Thanks. People like you make HN an enjoyable place.