Date: Thu Nov 26 1992 08:59:52 To: Richard Rearden Subj: abiogenesis Attr: science Rick, e

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Date: Thu Nov 26 1992 08:59:52 From: Jeff Otto To: Richard Rearden Subj: abiogenesis Attr: science ------------------------------- Rick, earlier you have questioned the probability of life spontaneously evolving. In other messages, I have posted extensively on the RNA world hypothesis. In the following messages, I address the chemistry involved in the synthesis of these precursor molecules, I posted the following messages back last august in the SCIENCE echo. Recently, it has been requested that the material be posted once again. I have not kept up with the field as much as I would have liked (my own thesis work taking more and more of my time these days), and consequently, have little to add to the following text. The one addition is that further evidence is accumulating that the functional parts of snrps (small nuclear riboproteins), is in fact the RNA. I got this information second hand from a biochemist (Stephen Monroe), who atttended an RNA meeting late last summer. If anyone can update what I have here, or address the role of lipid formation in early biological systems, I would be greatly indebted. The bottom line remains the same. The following does not prove that this is the way that life first evolved. Rather it indicates a possible scenario where life might have evolved. From this, even with its problems it is clear that the chemistry of the compounds of which we are made is such that abiogenesis could occur. A further distinction should also be made. The following has no bearing on evolutionary theory. Evolutionary theory would predict the same regardless of: special creation, space men, abiogenesis or anything else. It only predicts change in the frequency with which certain alleles exist in a population as environmental forces act upon that population. Jeff Otto 3-30-92 ==================================================================== Chuck Maier has requested that I post a detailed message involving a possible biochemistry of abiogenesis. The following messages contain my comments on the matter. The following are various organic/biochemical reactions that may have occurred on primitive earth. The reactions are taken directly from the text Biochemistry by Geoffrey Zubay, the second edition, 1988. To be honest, I though this text was more comprehensive that it appears to be. In order to address abiogenesis, one first must decide what would be required for a primitive "living" system. Based on the studies of Thomas Cech, Norman Pace, Sidney Altman, and Alan Weiner, I would suggest that a membrane encapsulated system containing RNA or an RNA like molecule would be sufficient. This is based upon experiments which have demonstrated that RNA can perform the following: 1) act as a polymerase and direct template specific synthesis of RNA 2) act as a site specific nuclease to cleave RNA 3) act as polymerase and direct template independent synthesis of RNA The result of these reactions is a molecule that under different ionic conditions can replicate, and release the products of replication via cleavage. To my way of thinking, in order to optimize the concentrations, and allow for somewhat adequete conditions for a self replicating system, it should be self contained, thus a membrane would be important if not required for our first "living" organism. It is quite possible that the earliest life forms performed these required reactions by nucleating in pockets of salt water saturated clays. Eventually however, a membrane is required. You should not from the above discussion assume that proteins are not required for this most primitive of scenarios. Beyond this, there is circumstantial evidence that would support RNA's role in primitive life. First of all, it is completely ubiquitous and absolutely required for life of all known systems. No known biological systems can survive without RNA. DNA viruses have to go through an RNA intermediate. Not all RNA viruses require a DNA intermediate. This is an important distinction. Secondly, increasing evidence has demonstrated that it is the RNA in ribosomes that is critical for protein synthesis, not the proteins. It appears that the proteins are more of a scaffolding, while the RNA performs the catalytic function. Thus we have evidence of yet another role for RNA - that for polypeptide synthesis. Furthermore, RNA has been implicated in maintenance of telomeres, which is important to prevent loss of genetic information in each round of replication. Other groups have also implicated RNA as a catalyst involved in carbohydrate metabolism. From these examples it is clear that no other molecule is nearly as wide reaching in its biological implications as RNA. Now, what is required to form an RNA molecule, and is it reasonable to expect that these molecules may have formed spontaneosly on primitive earth? To answer the first part, you need bases, a sugar and phosphates. To answer the second part, the answer is yes, and no. Although the arguments are certainly not definitive, they are currently the best ones that I am aware of, although it is entirely possible that I have missed important research in this area in the last few years. The next message(s) will detail these reactions and my comments on them. Much to my regret, the text that I have does not supply the reactions for lipid synthesis or sugar synthesis. The lipid reactions I have completely forgotten and will have to ignore. The sugar reactions, I remember a bit more of, and will try to recount what I can. First, I will discuss the biochemistry required for synthesis of the purine bases adenine and guanine. Under conditions postulated to have occurred on primitive earth, all of these reactions have been shown to occur, and the resulting end products are major products of the precursors. H2N CN This is diaminoaleonitrile, a \ / relatively simple product, easily HCN ---> C synthesized from hydrogen cyanide || C / \ H2N CN | | Now add a little ionizing radiation | and another molecule of HCN and we V get: NC N \ / \ \ A mess. Organic molecules do C not lend themselves well to this || C media. Seriously though, you get C / 5-aminoimidazole-4-carbonitrile / \ N which is a direct precursor of H2N adenine. Just add HCN | | HCN V NH2 | N N // \/ \\ | || C \\ / \ / N N By adding H2O to 5-aminoinudazole-4 carbonitrile you get a precursor of guanine | | H2O V O Is it my imagination or are || N my drawings getting better? / \ / \\ anyways, now just add a little H2N || C cyanogen and voila! / \ / H2N N H | | (CN)2 | V O || N HN/ \ / \\ Here is guanine. So the purines | || C seem easy enough to make. Lets /\\ / \ / try some pyrimidines now. NH2 N N H Fortunately at least one pathway for pyrimidine synthesis is a bit less complicated than for the purines. For the sake of brevity I will post it here, if you are genuinely curious, you can find all of this in the text cited in the first message. NH2 O HC | || ||| NCO- //\ H2O / \ C ------> N C -----> HN C C | || | || N //\ / //\ / O N O N H H Cytosine Uracil So now we have four bases. The next step is the sugar. To me, this is the biggest problem of the whole thing. Not because sugars would not form spontaneously under these circumstances, but because of the exponential nature of stereoisomers that can form with each additional carbon atom. The number of separate 5 carbon sugars is high enough to make the selection of ribose seem prohibitive. Some researchers think that glycerol or another similar sugar may have evolved first, simulating the structure that would later be achieved through ribose. Such a structure might look like: O Base \ | C H H / | C - C H OH OH Where as ribose looks like: * HOCH O Base \ / \ | C C /\ H H / | H C - C H OH OH * ** * denotes carbons involved in forming nucleotide polymers ** denotes hydroxyl groups required for RNA catalytic activity. As can be seen in the above diagrams glycerol supplies the critical catalytic hydroxyl, but lacks the carbons required for polymerization. To me, this is critical, and needs to be resolved, but until such a time it is the most current thinking. As for the phosphates, suffice it to say that they are added fairly easily. I will look for the lipid reactions, and if I can find them, I will post them along with the phosphate reactions. I hope everyone has found this interesting and informative. Jeff

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