Post of the Month: April 1998
by Ian Musgrave
On 1 Apr 1998 00:12:13 -0500, "RD Heilman" <firstname.lastname@example.org> wrote:
>email@example.com wrote in message
>>In article <aTnS.firstname.lastname@example.org>,
>> "RD Heilman" <email@example.com> wrote:
<snip intro re: "party-line" to focus on the following issues>
>>If there is anything resembling a party line concerning abiogenesis it
>>is that abiogenesis most probably happened spontaneously. As to exactly
>>how it might have happened there is no agreement whatsoever (though the
>>RNA world hypothesis seems to be winning).
>Yes, but still this is a far cry from a living organism. Unless we call the
>world where RNA molecules are able to replicate themselves, serving as
>their own enzyme,*living*. Not that I am suggesting anyone does. But where
>does this leave us?
At the first stage of development of organisms we would recognize as living. From self-replicating ribozymes, you could progress to say, ribozymes in liposomes, to membrane bound ribozymes with amino acid co-catalysts, to ribozymes coding for proteins . Step by step you progress toward something we would recognise as an organism (but not, of course a modern one).
>From what I have read replicating molecules is rather
>easy done in a modern lab. For example:
>Sol Spegelman in the 60s experimented with a supply of virus which he
>placed in a test tube, enriched a supply of the replicase enzyme that was
>required by the virus in order to replicate its RNA and an ample supply of
>free nucleotides. After he mixed these, and arranged a flow of materials
>into the system, he waited to see what happened. In the beginning the
>RNA copied itself rather faithfully. However, mutations quickly started
>cutting the RNA strands in half. These strands became increasingly
>shorter until after about 70 generations the RNA lengths stabilized at
>the shortest possible length capable of replicating itself. This strand
>contained about 220 nucleotides, little more than the recognition sight
>for the replicase enzyme. This molecule, labeled the Spiegelman Monster
>was able to reproduce itself at a fantastic rate in this protected test
>tube environment. But could not survive in the unprotected world,
>to say nothing of its survival in the primordial ocean.
Why would it not survive in a prebiotic world, where there are no competitors? 
>Manfred Eigen took the experiment one step further and started his
>experiment without the seed virus and with essentially the same results.
>This gave support to the naked gene hypothesis, which proposed
>that the first RNA consisting of a hundred or so nucleotides having
>only one purpose - to replicate themselves. But what are the chances
>of such a self - assembling molecule happening in the primordial
>seas, not to mention surviving.
Quite good actually. There are 1.6 x 10^60 possible 100 nucleotide sequences. In a primordial ocean of 10^24 litres with a nucleotide concentration of 10^-6M (reasonably dilute), assembling a 100 nucleotides sequences on clay al la Ferris  and assuming it takes a week to make a full sequence, then you can have produced roughly 1 x 10^50 sequences in a year! As it has been estimated that one in every 1 x 10^17 random RNA sequences is a high efficiency ligase , the chances of getting at least one self-replicating polymerase (or small self replicating assembly) is quite high.
Survival should be quite good, polynucleotides are quite stable (in the order of thousands of years), and there are no competitions to gobble them up, so a replicating ribozyme should come to dominate any lake or ocean it is in. With competition for resources, variants of the original ribozyme will come to dominate in certain environments.
>A second problem is the Gene-Protein linkup problem.
>The noble prize winning chemist, Walter Gilbert built upon the above
>work as well as the contributions of Orgel and others. Orgel succeeded
>in getting RNA to form new molecules in an energy rich nucleotide
>units then form new RNA chains matching the existing ones. They then
>automatically would form the double helix configuration. Gilbert proposed
>a scenario for the emergence of life. Beginning with self-catalytic ability
>needed to assemble themselves from the soup. Followed by
>recombination and mutation in order to explore new functions. Then the
>RNA molecules formed proteins. The protein enzymes are encoded by RNA.
>Finally the DNA appears giving a stable error correcting store of
>information. The main RNA functions, were then taken over by its creations, the protein
>The problem with this scenario is the same as with the others - getting the
>first step: getting the self - replicating RNA which experimentally comes only from
>present day modern RNA. Thus, the question is, how far have we come
>from the requirement for first life?
RNA (or RNA lookalikes ) can be generated abiotically, and RNA (or RNA lookalikes) can polymerize on clay substrates. Under plausible abiotic conditions virtually all possible 100 nucleotide sequences could be produced in under a billion years. We have come quite a long way.
<big snip re abiogenesis definitions>
>>The problem is that when you said
>>"then biological evolution would have no foundation,
>>since biological evolution proceeds only through natural
>>processes. And so, it seems a logical extension that life
>>must have also originated in the same manner." you seem to be
>>saying that if abiogenesis cannot be shown to be possible then
>>biological evolution must similarly be impossible
>I can accept your contention that abiogenesis is distinct from
>biological evolution, nevertheless it is a continuous and unbroken
>chain, beginning with or before the appearance of the
>self-replicating RNA which mutated, recombined and progressed
>up through the stage where it began to synthesis protein,
>enzymes and DNA. This process continued to mutate, the most
>efficient pre-cursor to life replicating and leaving the most
>offspring thus prenatural selection is born(?). This process
>continues to replicate and mutate until the first living biological
>entity appears. This first living entities continue to replicate,
>mutate, and become increasing complex. The first bacteria,
>blue-green algae, etc. appears and these or some relative
>prokaryote cells enter into a symbiotic relationship thus the
>first primitive eukaryotic cells are born. Long before this
>juncture ie the appearance of eukaryotic cells *evolution*
>was well on its way. But to call the process from the first
>RNA molecule to the first living entity is not evolution. Just
>how arbitrary is the break in this continuous process where
>non-evolution ends and evolution begins?
Evolution begins when you have replication, heredity (as you can have replication without heredity in some hypercycle systems) and selection of variant copies. So you could be justified in applying this to the first self-replicating RNA ribozyme. However the events leading up to the first self-replicating RNA ribozyme (prebiotic nucleotide synthesis RNA polymers assembled on clay, non-self replicating hypercycles) are not evolution.
Yes it is hard to decide what is the dividing line, even today it is hard to call the line between living and non-living (is a virus alive? it can replicate and evolve, a prion?). This in itself suggests that life is a natural process rather than divine fiat or deliberate construction.
>>when they do
>>not, in fact, work in the same manner at all, except insofar as
>>both are thought to be natural processes. Biological evolution
>>has been demonstrated to work, to the satisfaction of the vast
>>majority of scientists. Abiogenesis has not, but since they are
>>separate issues this does not make anyone doubt the veracity of
>Is this a fair question: is abiogenesis and evolution distinct because
>abiogenesis is poorly supported, consequently, it can lend no support
>to evolution? But then neither can it throw into question the veracity
>of evolution. So how can we know whether or not this is a protective
Abiogenesis and evolution are distinct because they involve distinctly different natural processes.
<snip more stuff>
>>Pasteur's experiment has demonstrated that water in a sterile
>>test-tube will not result in abiogenesis in a century or two (I believe the
>>test-tube is still on display in Paris). That hardly demonstrates that
>>life cannot arise from non-living matter on an entire planet full of
>>chemical reactions over the course of thousands or millions of years.
>Here again the proof is in the pudding. And there is scant evidence to the
>contrary. Pasteur also experimented with broth that had been sterilized
>(boiled). Then by using a flask with a crooked neck, in order to keep out
>microbes, was he able to demonstrate his hypotheses. Since microbes
>did not reach the sterile broth living organisms could not or did not
>appear. Thus, proving his hypothesis that life comes only from pre-existing life.
Again, no one is expecting an "amino acids to cyanobacteria" type transition that this implies. Furthermore, a litre or so of broth sitting quietly in a glass container for a century and a half is nothing like the primordial earth, where billions of litres of reactive chemicals in the ancients seas are churned by waves and mixed on catalytic clay and sand beaches, and even in this situation we might expect millennia to pass before we see something that could be defined as life (See Lacano refs at ).
>One thing is certain by removing the origin of life to an inaccessible time
>and place, researchers can never falsify the theory of the origin of life
>regardless of what theory scientist may advance. Consequently, they can
>experiment until their hearts are content with whatever results, great or
>small, they may obtain. No cynicism meant. just a statement of fact
>(as I see it).
This isn't true. The origin of life is placed where it is by evidence. As more evidence is accumulated various scenarios can be eliminated (as some have), new types of tests can be devised. Not long ago we had no way of detecting fossil bacteria, now we can. With more research we will undoubtedly be able to think of new ways of accessing these past times.
 Here I am giving only one possible scenario, others include "protein hypercycles first, then RNA/DNA" and "protein/RNA co-development".
 I am aware that this example required a pre-existing polymerase and that as well as the RNA , a polymerase would have to be around. However, in the prebiotic world this polymerase would not have to be anything like modern polymerases, even clay might do nicely, and so polymerase availability is not as limiting as in a modern example.
Ferris JP, Hill AR Jr, Liu R, and Orgel LE. (1996 May 2). Synthesis of long prebiotic oligomers on mineral surfaces [see comments] Nature, 381, 59-61.
Ekland EH, Szostak JW, and Bartel DP. (1995 Jul 21). Structurally complex and highly active RNA ligases derived from random RNA sequences. Science , 269, 364-70.
Miller SL. (1997 Mar). Peptide nucleic acids and prebiotic chemistry Nat Struct Biol , 4, 167-9.
Hager AJ, and Szostak JW. (1997 Aug). Isolation of novel ribozymes that ligate AMP-activated RNA substrates Chem Biol , 4, 607-17.
James KD, and Ellington AD. (1997 Aug). Surprising fidelity of template-directed chemical ligation of oligonucleotides [In Process Citation] Chem Biol , 4, 595-605.
Schwartz AW. (1997 Aug). Speculation on the RNA Precursor Problem J Theor Biol , 187, 523-7.
Bolli M, Micura R, and Eschenmoser A. (1997 Apr). Pyranosyl-RNA: chiroselective self-assembly of base sequences by ligative oligomerization of tetranucleotide-2',3'-cyclophosphates (with a commentary concerning the origin of biomolecular homochirality). Chem Biol , 4, 309-20.
Bohler C, Nielsen PE, and Orgel LE. (1995 Aug 17). Template switching between PNA and RNA oligonucleotides Nature , 376, 578-81.
Lazcano A, and Miller SL. (1996 Jun 14). The origin and early evolution of life: prebiotic chemistry, the pre- RNA world, and time. Cell , 85, 793-8.
Ertem G, and Ferris JP. (1996 Jan 18). Synthesis of RNA oligomers on heterogeneous templates. Nature , 379, 238-40.
Ishizaka M, Ohshima Y, and Tani T. (1995 Sep 14). Isolation of active ribozymes from an RNA pool of random sequences using an anchored substrate RNA. Biochem Biophys Res Commun , 214, 403-9.
Peta, Ian and Jack Francis
reynella at werple dot mira dot net dot au
Aitch Tee Tee Pee colon slash slash werple dot mira dot net dot au slash tilde reynella
Terry Pratchet fans, tree planters and sometime scientists (De Chelonian Mobile!)
First posted 2 April 1998
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