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Author Topic:   Self Replicating molecules
singularity
Inactive Member


Message 1 of 25 (14377)
07-29-2002 6:50 AM


Hi All

I found an article which may be of interest if you can access it.

Journal of the American Chemical Society
Vol. 124, No. 24 June 19, 2002
Approaching Exponential Growth with a Self-Replicating Peptide
Roy Issac and Jean Chmielewski pp 6808 - 6809

The abstract is:

---------

Self-replicating peptide systems hold great promise for a wide range of technological applications, as well as to address fundamental questions
pertaining to the molecular origins of life. The development of self-replicating compounds capable of high efficiency, however, has remained elusive.
Here we disclose a successful strategy whereby modulation of coiled-coil stability results in remarkable catalytic efficiency for self-replication. By shortening the peptide to the minimum length necessary for coiled-coil formation a highly efficient self-replicating system was obtained due to very low background reaction rates, bringing the efficiency close to naturally occurring enzymes.

-----------

The system consists of two different short polypeptide chains (13 and 14 amino acids long) which naturally adopt a helical conformation which can be joined to produces a longer peptide. Three longer peptide chains will spontaneouly aggregate into a trimer, which then binds one of each of the two shorter chains and causes them to join together to form a fourth long peptide. One long peptide dissociates from the complex and the catalytic trimer is reformed.

On the upside the sequences are completely designed by humans, so you can't argue that they are just a copy of divine origin. They also only contain five different amino acids, which simplifies things. One of the peptide chains is chemically activated though (with a reactive thioester group) so the dice are definitely loaded energetically. It does nicely demonstrate the principle of self replicating molecules though and the kinetics are almost as efficient as real enzymes.

This is undoubtedly a simple and idealised system. I think a historical perspective is required though. Do we look back on the simple experiments of Newton as inadequate and incomplete foundations for his theories or do we admire his vision and determination? You may argue that scientists are nowhere near demonstrating that abiogenesis ever took place, but can you argue that this isn't a step in the right direction?

Shane


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singularity
Inactive Member


Message 10 of 25 (14592)
07-31-2002 8:14 PM
Reply to: Message 9 by axial soliton
07-30-2002 2:22 AM


I don't think you can readily define a threshold between molecules that self replicate and those that don't- its only a matter of efficiency and how picky they are about their environmental requirements for replication. It is a high dimensional problem so any "interfaces" will be necessarily fuzzy.
This message is a reply to:
 Message 9 by axial soliton, posted 07-30-2002 2:22 AM axial soliton has responded

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 Message 12 by axial soliton, posted 08-02-2002 2:23 AM singularity has responded

  
singularity
Inactive Member


Message 13 of 25 (14804)
08-03-2002 11:59 PM
Reply to: Message 12 by axial soliton
08-02-2002 2:23 AM


The salt example is an excellent analogy of how simple self replication can be when you consider that a salt crystal can act as a nucleus for crystallisation in a supersaturated solution. Life by analogy is a vastly more complicated crystallisation/coalesence that occurs in a system where a thermodynamic gradient exists and a starting structure (seed/spore etc) is present which can tap into that energy is present also.

I think the signposts to what is self replicating and what is life will be arbitrary. You only have to consider the unresolved issue of whether or not viruses are worth considering alive. The virus example is a good point as it requires a very complex biological environment in which to behave in a manner akin to life. In the peptide example I posted you also need a specific environment where the appropriate conditions and substrates are present. I think the sign posts will be arbitrary because it is a simple thought experiment to take a living cell and limit its complexity in a step wise manner where every loss of a function places limitations on the environment in which it can survive. For example you could remove its capacity to synthesise the amino acid tryptophan, placing a limitation on its environment to one that contains sufficient exogenous tryptophan. This process can be extended endlessly until the cell IS the environment.

Shane


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 Message 14 by axial soliton, posted 08-04-2002 2:44 AM singularity has responded

  
singularity
Inactive Member


Message 16 of 25 (14933)
08-07-2002 12:35 AM
Reply to: Message 14 by axial soliton
08-04-2002 2:44 AM


I meant arbitrary on the basis that it always comes down to someone subjectively deciding if something qualifies as life (including ourselves on our more philosophical days ), to which there will always be differing views. It is like trying to define the difference between a fried egg and a scrambled egg. Sure we all know what the traditional definitions are but it is quite easy to imagine everything in between. Names apply to extremes and continuitites underlie everything we describe. To clarify I am not saying that the nature of life is arbitrary- just the borders of what should be considered as living or nonliving.

Carbon is an exceptional element, but the 6/6/6 observation isnt the key to its adaptability and intergrity to living systems. For instance bacteria are routinely grown in 13C containing media (six protons, six electrons and seven neutrons) and 14C media (six, six and eight) with no major effects except from the low level radioactivity of the latter. The versatile bonding and redox behaviour of carbon adequately explains its utility in living systems. I don't think the question about folding DNA makes sense- there is carbon throughout the molecule so of course it is involved at folding sites, along with oxygen and phosphorous primarily. Your enzyme question is also very confusing.


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 Message 14 by axial soliton, posted 08-04-2002 2:44 AM axial soliton has responded

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 Message 17 by axial soliton, posted 08-07-2002 4:34 PM singularity has responded

  
singularity
Inactive Member


Message 18 of 25 (15020)
08-08-2002 5:27 AM
Reply to: Message 17 by axial soliton
08-07-2002 4:34 PM


Hi Axial

My instinct is after reading your theory that it sounds like a long shot (but what good is instinct?! ). It brought up memories of a few papers I have seen on DNA conducting electricity over short distances (a tunneling effect from memory) and some recent observations that proteins vibrate in a manner which is seems to be part of the basis of their catalytic activity. Sorry no detailed references- it was a long time ago and only in passing. I am not familiar with conductivity in carbon nanotubes, but expect that their expectional properties will not be applicable to biomolecules even over short distances.

I agree that there probably is a boundary between life and nonlife, but as I think it will be polydimensional and dependent on definitions and assumptions (and therefore in my mind artificial). The article you cited on retrosposons being wide spread was interesting, but they arent definitive proof an "RNA world" ever existed.

From my lessons on chemical bonding I remember being told that carbon's versatility is a product of its variable hybridisation and oxidation states and efficient orbital overlap (small nucleus effect I guess). Sulfur for example is also capable of catenation but is less versatile and the bonds are weaker because of the same factors. It is nice to imagine silicon based organisms but the truth is that life here already deals in it to a limited degree and would probably have utilised it if it was worthwhile. It is simply too happy being silicon oxide.

Where I loose faith in your theory is where it is implied that carbon-carbon bonds are essential to the phenomenon, yet DNA doesnt contain a continuous chain of C-C bonds. The basic units of the backbone are liked through phosphates (O-P-O) and even the bases and the sugars are separated by an oxygen.

There is aromatic pi electron stacking through the nucleobases in a manner not dissimilar to the packing of graphite sheets. I still don't understand what the resonance you talk about it actually supposed to *do*. Proteins interacting with DNA and RNA are dependent on local sequence and conformation only- as far as I know there is no unexplained influence of sequence at a distance that would require a different mechanism to explain. Interactions within DNA and RNA is mediated by complementary hydrogen bonding, which again acts locally.

Perhaps you can clear up some of my possible misinterpretations....

Shane


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 Message 20 by axial soliton, posted 08-10-2002 4:06 PM singularity has responded

  
singularity
Inactive Member


Message 21 of 25 (15178)
08-11-2002 4:11 AM
Reply to: Message 19 by Quetzal
08-08-2002 6:46 AM


I disagree totally that protein self replicators are necessarily incapable of mutation across generations. The interactions for catalysis are not simple yes or no propositions. Modifying single residues only changes the catalytic efficiency to some degree. The paper I cited made their catalytic system more efficient by making the peptides assemble less strongly, thus speeding up the rate of substrate exchange. Rates of nonspecific catalysis were observed for earlier model peptides...

I agree that peptides alone are unlikely candidates for first life, but they are no worse than any nucleotides or PNA. The biggest problem in abiogenesis is a big enough energy source to power catalysis. I was thinking about this recently and wondered if elemental iron and carbonates could react to give iron oxides and reduced forms of carbon- perhaps catalysed by iron sulfur complexes which still form the core of all biological energetic systems. I just found a good link which supports the basic idea:

http://www.nature.com/nsu/000224/000224-3.html

So much of the hard work of living systems is controlled by very inorganic looking systems, such as iron-sulfur in metabolism and metals in enzyme catalysis.

Any comments?

Now actually getting to pRNA or PNA outside a lab is a bit more chancy. Both require pretty stringent conditions. Guess where the creationist designer/god is currently located?

[/B][/QUOTE]


This message is a reply to:
 Message 19 by Quetzal, posted 08-08-2002 6:46 AM Quetzal has responded

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singularity
Inactive Member


Message 22 of 25 (15179)
08-11-2002 4:25 AM
Reply to: Message 20 by axial soliton
08-10-2002 4:06 PM


>I have always wondered why DNA comes in only 1 handedness. Has this
>anything to do with supporting properties of replication?

The handedness of DNA is due to the handedness of the sugars in the back bone. They simply wont bend the other way, but using the enantiomers of the sugars would give a helix with the opposite handedness. The chirality of life may just be a detail- there is no reason to believe why an organism cant be a molecular mirror image of itself, except of course that interactions are also chiral and it would have trouble living in a world with the opposite chirality. It may just be a convenience for organisms to deal in one kind of enantiomers for the basic building blocks- a metabolic common currency to support a free market

I still don't see DNA acting as a long range wire in vivo- for one thing there is no known plausable mechanism for providing the necessary electrochemical energy up and down the helix that I am aware of.


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 Message 20 by axial soliton, posted 08-10-2002 4:06 PM axial soliton has responded

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