Why Life Must Start with RNA and not Something Else.

In the previous post, I argued that reproduction had to start with RNA, but that leaves the obvious question, why not something else? The use of purines and pyrimidines to transfer energy arises simply because the purines and pyrimidines are the easiest to form, given the earliest atmosphere almost certainly was rich in ammonia, hydrogen cyanide, cyanocetylene, and urea would soon be formed. Some may argue with the “easily formed”, however leaving a sample of ammonium cyanide and urea to its own devices will get nucleobases. Cytosine is a little more difficult, but with available cyanoacetylene, it is reasonably likely. The important point is that if you accept my mechanism for how rocky planets form, these chemicals are going to be prolific. I shall justify that later. The important thing about these chemicals is that they lead to the formation of multiple hydrogen bonds only with their partners. As explained in the last post, there is no alternative to hydrogen bonds for transferring information, and these are the only chemicals that can provide accuracy under abiogenic conditions.

The polymer linking agent is phosphate, so why phosphate? Phosphoric acid has three hydrogen atoms that are available for substitution, i.e.it can form three functions. Two are to form esters and as I noted previously, the third is to provide solubility. The solubility is important because if there was not anionic repulsion, the strands would bundle together and reproduction would not work. The strands would also not provide catalysis, which occurs because a strand can fold around a cation like magnesium and form the shapes that seem to be needed. The good news is that unlike in enzymes, it can rearrange the magnesium and thus get different effects. Of course, enzymes are hugely more effective, but an enzyme generally only does one thing.

The polymer forms esters by phosphate bonding to a sugar. Think of the reaction as

P – OH  + HO – C    ->  P – O – C  + H2O       (1)

where P is the phosphorus of a phosphate or phosphoric acid, and C is the carbon atom of a sugar. Note that this reaction is reversible, but at room temperature the bonds are quite stable. These ester bonds are very strong, which is important because you do not want your carefully prepared polymer to randomly fall to bits. On the other hand, it must be able to be disrupted or substituted and not be essentially fixed, as would happen if proteins were used for information transfer. The reason is, life is evolving by random trials, and it is important that since many of these trials will be unproductive, there has to be a way to recover an many of the valuable chemicals as possible for further trials, and also to unclutter the system so that something that conveys advantages does not get lost in the morass of failures or otherwise useless stuff. Only phosphate offers these properties. In principle, you might argue for arsenate, but its bonds are weaker, thus less reliable, and worse, arsenic reacts with hydrogen sulphide (common around fumaroles which as we shall see are necessary sites) to form insoluble sulphides. These are the very pretty yellow layers in geothermal areas. No other element will do.

There are a variety of other sugars that if used to link nucleobases to phosphate will form duplexes, so the question then is, why weren’t they used? The ability to catalyse its own scission is the first of two reasons why ribose is so important. Once the strands get long enough to fold around themselves, catalysis starts, and one of the possible catalytic reactions is the promotion of the remaining OH group on the ribose to help water send the reaction (1) into reverse, which would break a link in the polymer chain. Deoxyribose does not have such a free hydroxyl and hence does not have this option, which is why DNA ended up being the information transfer chemical once a life form that had something worth keeping had emerged. What this means is that RNA has the opportunity to mutate, which is a big help in getting evolution going, and when it is broken, the bits remain available for further tries in some rearranged form.

The question then is, how do you form the phosphate ester? You mix phosphate and the sugar in solution and – oops, nothing happens. Reaction (1) is so slow at ambient temperature that you could sit there indefinitely, however, if you heat it, it does proceed. However, the rate of a reaction like this depends on the product of the concentrations on each side, with such a product on the right-hand side determining the rate of the reaction going from right to left. If you look at (1), it probably occurs to you that in aqueous solution, the concentration of water is far greater than the concentration of sugar. You will see people say that life could start around black smokers, but when you check, at the temperatures they require for the forward reaction to go it requires the concentration of water to be less than about 2%. Good luck getting that at the bottom of the ocean. You may protest that nevertheless there is life there, devouring emerging nutrients. True, although the ocean acts as a cooling bath, and the life forms have evolved protective systems. There are no such things when life is getting started. Life has moved to be close to black smokers but it did not start there.

What we need is a more precise way of delivering the required energy to the reaction site. So far, one and only one method has been found to make such initial linkages, and that is photochemical. If adenine is irradiated with light in the presence of ribose and phosphate, you get AMP, and even ATP. We now see why only ribose was chosen. AMP, and for that matter, RNA, link the nucleobases and phosphate through the ribofuranose form. Such sugars can exist in two forms: a furanose (a five-membered ring involving an oxygen atom linked to C1 of the sugar) and a pyranose form (the six-membered equivalent.). Now the first important point about a sugar is it cannot transmit electronic effects arising from the nucleobase absorbing a photon. However, it can transmit mechanical vibrational energy, and this is where the furanose becomes important. While the pyranose form is always rigid, the furanose form is flexible. The reason ribofuranose can form the links, in my opinion, is it can transmit and focus the mechanical energy to the free C-5 which will vibrate vigorously like the end of a whip and form the phosphate ester. Ribose is important because it is the only sugar with a reasonable amount of furanose form in aqueous solution. It is also worth noting that in the original experiments, no phosphate ester was formed from the pyranose form. As the furanose is used, the equilibrium ensures pyranose maintains the furanose/pyranose ratio.

That leaves open the question, how are the polymers formed? It appears that provided you can get the mers embedded in a lipid micelle or vesicle (the most primitive form of the cell wall), leaving these in the sun on a hot rock to dry them out leads to polymers of about 80 units in an hour. This is the first reason why life probably started around geothermal vents on land. Plenty of hot rocks around, with water splashes to replenish the supply of mers, and sunlight to form them. The second reason will be in the following post.

The title statement can now be answered. Life must start with RNA because it is the only agent that can lead to biological reproduction without external assistance. I started the last post indicating I would show what sort of planets might harbour life. The series is nearly there, but some might like to try the last step for themselves.

8 thoughts on “Why Life Must Start with RNA and not Something Else.

  1. Science Fiction writers, and even some exobiologists seemed to have suggested that exotic life forms, not carbon based, could develop. However, Carbon, Oxygen are most frequent, and most reactive, so carbon based life seems more likely.
    Now you are saying that actually life should start, roughly as we know it… with RNA. RNA is most natural, considering the abundance of its basic elements.

    What happens in synthetic DNA, which are now being made? Are they also less natural?

    • Hello Patrice. Everything life does is based/powered through chemistry, so you need the chemicals to be based on an element that can form a lot of reasonably strong bonds but of roughly equal energy so that you can use a whole lot of different chemicals to do various tasks. Now, suppose you chose silicon as a carbon replacement. As soon as it comes into a reaction with oxygen (including in water) you find the Si – O bond is so much stronger than anything else and that bond almost never breaks. Accordingly, all silicon atoms end up as rocks, and they don’t do anything. Rocks never show the slightest sign of life. Only carbon can form these sort of bonds. Also, silicon-oxygen bonds, other than in silicic acid, seem incapable of participating in hydrogen bonds, and silicic acid seems to slowly convert itself into quartz.

      Yes, I am saying that RNA is the only place you can start with reproduction from abiogenic conditions. I am not sure what you mean by synthetic DNA. If you mean DNA made in the lab, no it is not natural. But if you mean DNA synthesised by enzymes, yes, that is natural, but it could not be part of the start. There is no way DNA can appear under abiogenic conditions, because you can’t make 2-deoxyribose before enzymes appear.

  2. As Patrice mentions, I’ve wondered if there might be something that could be called “life” that’s totally different from what we identify as such. Your explanation of the basics provides a perspective I haven’t thought about before, but I suppose the answer comes down to a definition of “life,” which I think you provided in the post before this one. These things are always worth thinking about, so thanks for providing fuel for that process, Ian!

    • Yes, Audrey, it does depend to some extent on what constitutes life. I am not saying reproduction is the only thing, but I feel if it cannot reproduce it isn’t life. There may be an issue later with artificial intelligence – it is alive? But for the moment I am considering what could have arisen from the fabled primordial soup.

  3. Hi Ian and Audrey, here is what I meant, “Unnatural Base Pair”, extracted straight from Wikipedia. Before I give that quote, I wonder if Ian’s assertion that all life has to start with RNA is affected by UBP. This is all cogent and practical, as it seems to me that the probability of microbes on Mars is high… And Mars colonization is one functioning thermal nuclear rocket away…

    Unnatural base pair
    DNA sequences have been described which use newly created nucleobases to form a third base pair, in addition to the two base pairs found in nature, A-T (adenine – thymine) and G-C (guanine – cytosine). Multiple research groups have been searching for a third base pair for DNA, including teams led by Steven A. Benner, Philippe Marliere, and Ichiro Hirao.[34] Some new base pairs have been reported.[35][36][37]

    In 2012, a group of American scientists led by Floyd Romesberg, a chemical biologist at the Scripps Research Institute in San Diego, California, published that his team designed an unnatural base pair (UBP).[3] The two new artificial nucleotides or Unnatural Base Pair (UBP) were named d5SICS and dNaM. More technically, these artificial nucleotides bearing hydrophobic nucleobases, feature two fused aromatic rings that form a (d5SICS–dNaM) complex or base pair in DNA.[4][38] In 2014 the same team from the Scripps Research Institute reported that they synthesized a stretch of circular DNA known as a plasmid containing natural T-A and C-G base pairs along with the best-performing UBP Romesberg’s laboratory had designed, and inserted it into cells of the common bacterium E. coli that successfully replicated the unnatural base pairs through multiple generations.[34] This is the first known example of a living organism passing along an expanded genetic code to subsequent generations.[4][39] This was in part achieved by the addition of a supportive algal gene that expresses a nucleotide triphosphate transporter which efficiently imports the triphosphates of both d5SICSTP and dNaMTP into E. coli bacteria.[4] Then, the natural bacterial replication pathways use them to accurately replicate the plasmid containing d5SICS–dNaM.

    The successful incorporation of a third base pair is a significant breakthrough toward the goal of greatly expanding the number of amino acids which can be encoded by DNA, from the existing 20 amino acids to a theoretically possible 172, thereby expanding the potential for living organisms to produce novel proteins.[34] The artificial strings of DNA do not encode for anything yet, but scientists speculate they could be designed to manufacture new proteins which could have industrial or pharmaceutical uses

    • Hello Patrice and Audrey,
      Different base pairs are theoretically possible, but the problem is how are they made? The advantage of the ones RNA uses is that all we need is ammonia, hydrogen cyanide, urea, and cyanoacetylene, all of which can be reasonably expected with the right starting materials, which I shall deal with in a later post.

      You will note also that RNA does not use Thymine, presumably because it could not form by itself without some enzyme assisting it. RNA still uses uracil instead. Another point is that adenine is the easiest purine to form, and it will always be present in excess until there is more controlled synthesis. The initial part of RNA controlling aminoacid condensation would also be limited by the availability of different aminoacids.

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