The metabolism first model of the origin of life

[CraigD]

I recently read NYU chemists Robert Shapiro’s “A Simpler Origin for Life” (6/07 Scientific American preprint), and found its ideas – more of a description of a biological paradigm and a comparison with an earlier paradigm than a theory – compelling.

 

The essence of what Shapiro and others call the “small molecule” or “metabolism first” model for the origin of life on Earth (prettily illustrated in the print and subscriber online versions of the article), and its contrast to the earlier “RNA first” or “replication first” model, is that early “life” – as described by a “thermodynamic definition of life”, to distinguish it from the usual definitions, which typically requires hereditary information storage (eg: RNA and DNA) – arose wherever conditions permitted energy-utilizing, cyclic chemical reactions in naturally occurring “containers” such as cavities in rock. Most of these reactions were neither self-sustaining nor tending to decrease local entropy, producing, as they tend to do today, organic tars and other “waste” results, but some, the model proposes were both, resulting in self-sustaining chemical systems. As other compounds “hitched a ride” on the dominant reaction cycles, eventually catalysts formed, giving the system a efficiency advantage, driving an evolution-like process. “Reproduction” was synonymous with “expanding into new containers”, and hereditary information was transmitted by a “compositional genome” – that is, a particular mix of molecules, rather than a code for producing and arranging molecules, as is found in modern, DNA-based life. These catalysts eventually became the first RNA molecules, from which point the “metabolism first” model merges with the “RNA first”, with RNA and later DNA assuming an information-storage role, enabling the evolution of the complex life we find today.

 

A major virtue of the metabolism first model vs. the replication first model is that “metabolism”, according to the thermodynamic definition, appears many orders of magnitude more statistically likely than the chance assembly of the simplest replicator molecules, making it a “many less unlikely occurrences”, or gradual, model, vs. a “one very unlikely occurance” model – though estimating such probabilities is difficult, and, to date, appear to me unconvincing.

 

The metabolism first model and the “thermodynamic definition of life” hold a lot of intuitive appeal for me. Critics point out and proponents admit that the model lacks experimental support – even in simplified computer simulations, no one has yet shown an actual chemical process that results in the emergence of such proto-life. However, unlike the replication first model, which seems unlikely to be experimentally reproduced, there’s some hope that, via computer simulation and large numbers of chemical experiment, such a demonstration may prove possible.

 

Thoughts?

Edited August 9, 2015 by CraigD
Fixed broken link

[billg]

Fascinating.

 

I can't help but think the distinction is in fact based more on how you choose to define life than an actual difference in models. I'm not sure on the specifics of either, but surely anyone proposing the RNA model is not proposing the self-replicating RNA models simply emerged out of nowhere. Like any model of abiogenesis, the initial "spark" would be presumed to occur in a primordial soup rich in energy, complex molecules, and metabolism-like reactions. It seems to me the difference in models is where one calls this soup itself the "life", the other calls the first replicating molecules "life". This makes the advantage of the metabolism model being more statistically likely fairly meaningless; as you said, it merges with the RNA hypothesis, so it's really the same model with the same probability.

 

Personally, I think I'll stick with the RNA definition of life. All that we call life today involves RNA or DNA. RNA has the additional advantage of being not only "information storing" but the potential to act as a catalyst. I would suggest the promordial soup was merely the environment in which first life could have arisen, and not the life itself.

[Eclogite]

I don't see it as an either/or situation. The replication function may have been evolving in a non carbon based setting, such as Cairns-Smith's ideas on clays, while in parallel ever more complex metabolisms based on autocatalytic cycles were emerging. Then, at some point, the two came together - voila, life Jim, just as we know it.

[CraigD]

I can't help but think the distinction [metabolism vs. replication first] is in fact based more on how you choose to define life than an actual difference in models. I'm not sure on the specifics of either, but surely anyone proposing the RNA model is not proposing the self-replicating RNA models simply emerged out of nowhere.

My read of Shapiro’s summary of RNA/replicator first models is that, in essence, they do suggest that early self-replicating models emerged out of a “nowhere” of constantly changing molecules – the “primordial soup”. Another comparison between small molecule/metabolism first and large molecule/replication first models is that the former describe incremental, gradual change, while the later describe “catastrophic”, abrupt change.

 

There’s a very nice graphic in the print/subscription .pdf article contrasting the models, which I’ll try to summarize textually (and expand upon) here.

1. Both models: Small organic molecules (eg: amino acids) form from non-biological processes.
   
2. Metabolism First: Naturally occurring compartments present and necessary.
   Replicator First: Compartments not necessary or desirable. Large reactive soup preferrable
   
3. RF: Small molecule form chains
   MF: Small molecules participate in energetic reactions within and across container walls
   
4. RF: Most chains don’t replicate.
   MF: Most reactions aren’t self sustaining, ending in tars and other glops.
   Repeat step 3 until molecules that work for the model appear
   
5. RF: Number of replicating molecule increases geometrically, quickly outnumbering all others
   MF: Many dissimilar reactions of similar efficiencies exists, expanding linearly and competing for limited energy and reactants
   
6. RF: Replicating molecule mutate randomly.
   MF: Reaction cycles vary, including “side reactions” that neither help nor hurt the main reactions’ stability
   
7. Repeat step 6 until …
   RF: … genes to produce efficient metabolism, including ones to create films and/or cell walls (compartments), appear and quickly out-compete other genomes
   MF: … side reactions that catalyze (increase efficiency of) main reactions appear, allowing catalyzed reactions to slowly or quickly out-compete non-catalyzed ones. Compartments already exist
   
8. MF only: Repeat steps 6 and 7 until RNA-like catalysts capable of storing genetic information appear, and quickly out-compete others.
   
9. Both: Darwinian evolution
   

The two models can be characterized by very different external appearances:

• RF: (large) molecules in “soup”, then cells in soup
  
• MF: ooze (many smaller interacting molecules) in rocks, bubbles, etc, then cells in soup
  

Step 3 and 4 mark the critical argument for preferring MF over RF – MF proponents contend that the required number of repetitions of these steps for RF exceeds the time available for life to have formed, while the less improbable but more numerous required “lucky breaks” for MF do not.

 

Shapiro emphasizes that, despite compelling experiments such as 1953 Stanley L. Miller’s 1953 “spark in the soup” that showed that small amino acids could be formed non-biologically, nobody has a convincingly good estimate of the actual probabilities of the “repeat until” events required by both model – but that obtaining such estimates for MF, and thus proving or disproving its theoretical viability – is much easier than for RF. In a bit of rhetoric that apparently irked some of his RNA-first promoting colleagues, Shapiro compared “prebiotic synthesis”, the discipline of explaining steps 3 and 4 in RF models, to a person playing 18 holes of golf, then arguing that they had demonstrated in principle that a golf ball could “play itself around the course in his absence” – in short, accusing RF proponents of excessive wishful thinking.

Personally, I think I'll stick with the RNA definition of life. All that we call life today involves RNA or DNA. RNA has the additional advantage of being not only "information storing" but the potential to act as a catalyst. I would suggest the promordial soup was merely the environment in which first life could have arisen, and not the life itself.

I don’t see any problem with drawing the line for the origin of “true life” at the emergence of RNA. The two kinds of models differ only in when this occurred, and what preceded it. “Thermodynamic life” and “prebiotic” can, I think, reasonably be considered synonyms.

[CraigD]

I don't see it as an either/or situation. The replication function may have been evolving in a non carbon based setting, such as Cairns-Smith's ideas on clays, while in parallel ever more complex metabolisms based on autocatalytic cycles were emerging. Then, at some point, the two came together - voila, life Jim, just as we know it.

Cairns-Smith’s clay theory is intriguing – thanks for introducing me to it. I can’t work out, however, how it makes the jump from information-storing clay crystals, which have a lot of Si and few if any C bond (organic) molecules, to RNA or proto-RNA, which has nothing but C H O and N.

 

A bit off-topic I think “parallel evolution” provides the best explanation of complicated multicellular life. Rather than the DNA of simpler organisms “inventing” variant cells and plans for connecting them into tissues, I believe that much of multicellular life is the result of both “peer colonies”, in which one organism eventually encased the others, either incorporating them into its own nuclear DNA, or, as in the case of mitochondria, simply providing a safe container for them, and “invasion colonies”, such as bacteria and viruses, in which the genomes of former parasites and pathogens are incorporated into larger cells’ DNA. In a real sense, I think animals such as ourselves are “evolved walking biofilms/pond scums” :).

 

Such developments, if I’m correct in believing they occurred, were much later developments than the early life Shapiro and Cairns-Smith describe – making me guilty of hijacking my own thread! :eek2:

[Kayra]

Hmm, having been often compared to (or out and out called) pond scum on many a friday evening, I always brushed it off as a side effect of the alcohol she was drinking and how it affected her vision. It would appear the observation was more accurate then I thought.

 

As to Shapiro's theory, it appears to be much simpler and vastly more probable then any other I have encountered.

 

As you stated CraigD, it strikes an intuitive chord and I look forward to experiments testing it's achievability.

[Gregorio]

The dispute whether replication or metabolism came first is naive, and grows out of a lack of understanding about the nature of energy and how it manifests itself at the chemical level. The five requirements that Shapiro says metabolism must meet are all expressed in an equation, called Kleiber's Law, that relates metabolic rate to biological organism mass and metabolic efficiency. This equation differs from that version preferred by the quarter power scalers like Geoffrey West and James Brown. This latter equation has the value 3/4 for the exponent of mass, something that occurs only when metabolic efficiency is 100%.

 

Metabolic efficiency is defined by Lloyd Demetrius of Harvard, in the equation, as the ratio of the rate of reduction reactions to the rate of oxidation reductions, and is a statement then of the efficiency of redox coupling. A graph of this equation features metabolic efficiency on the X axis, and metabolic rate on the Y axis, with a different curve for each mass.

 

Examination of the graph with the thermodynamic pressure for metabolic rate to stabilize as background presumption, reveals that replication is part of metabolism, and takes place either to retrieve or prevent further perturbation in metabolic rate given changes in metabolic efficiency (in the exponent for mass).

 

The claims of Addy Pross in his "Causation and the Origin of Life...", to the affect that the metabolism first argument is experimentally unverifiable, unlikely, and trivial, are based upon a failure to understand that what he calls "kinetic pathways" boils down to electrochemistry, what Kleiber models in its relation to changes in the organization of the mass and to the size of the mass. This includes replication, whether the mass is a micelle, a phage, a cell, or a multi-cellular organism.

 

Pross ludicrously says that the work of Urey-Miller that involved electrical discharge in a prebiotic atmosphere to trigger the assembly of biological molecules like amino acids suggests that replication must have come first when, in fact, that very discharge is what metabolism is all about - electrochemistry acting upon atoms and molecules. Where replication comes in is where increases in metabolic rate from increases in energy availability (the denominator of the metabolic efficiency ratio) can only be absorbed by the mass through its division, its loss of mass.

 

I recommend that one study this equation and the graph of it, for it provides a whole series of testable inferences that vary from the use of electrochemistry to build muscle mass or to destroy and prevent cancer, to the use of that very same electrochemistry to stop and reverse the degeneration of aging. The equation clearly models how aging is a result of the antagonism of basal and field metabolic rates, where the increase of one translates to the diminution of the other, especially for all organisms over 25% efficient. In fact the equation defines a sort of universal metabolic attractor that occurs at 25% metabolic efficiency and one gram mass, where stabilization of perturbed metabolic rates with changes in metabolic efficiency (from food excess, starvation, activity, or mutation) is most easily accomplished.

 

Again, replication is part of metabolism, and not to be distinguished from it. The answer is in math and physics. Curiously, Kleiber, when viewed this way, reveals that evolution is about metabolism primarily, and genetics only secondarily. In fact the thesis of John Cairns in his 1988 "The Origin of Mutations", that mutation rates accelerate in bacteria exposed to stress from starvation, are modeled in this equation, as well as the findings of Paul MacClean that weight regain after dieting is facilitated by increased metabolic efficiency from dieting.

 

Contrast this with the arrogance of those in the DOEB at Harvard (one of whom is Lloyd Demetrius), in particular those in the Program for Evolutionary Dynamics (headed by Martin Nowak), who strut around wielding Nowak's 2006 book Evolutionary Dynamics and insisting they are going to reduce Darwin to a series of equations. Examination of Nowak's book reveals not a single equation dealing with metabolism, as if life began only with the RNA/DNA world. Those guys at Harvard are like hillbillies in the Appalachias. It turns out that Demetrius has never run the numbers in his own equation (I've never seen it anywhere else except in his 2004 paper on caloric restriction and the longevity of mice), and in emails to me he has confessed he doesn't know jack about either electrochemistry or metabolism, though he insists metabolic energy is quantized, just like the electron. Surprise! Metabolic energy IS THE ELECTRON, but that's another story beyond the conceptual capabilities of those who believe that bioelectricity involves diffusion gradients of ions and protons. That means all of neuroscience is incapable of understanding why encephalization is related to the evolution of longevity in mammals. Too bad.

[coldcreation]

I recently read NYU chemists Robert Shapiro’s “A Simpler Origin for Life” (6/07 Scientific American preprint), and found its ideas – more of a description of a biological paradigm and a comparison with an earlier paradigm than a theory – compelling....snip...

 

Thoughts?

 

I adhere to the notion that there is no begining of life, just a slow evolution, a transition, a kind of continuum that progresses from inanimate to animate, from inert to an organic physically alive state. In that context the concept or theory you write about is intreging (though I still have not read the original paper).

 

One thing is for sure; doors are opening outwards to a new and fruitful era in our pursuit of knowledge. Our understanding of what nature is and how it works is expanding, shedding light onto our ultimate goal, the grand aim of all science and indeed of all humanity: understanding life and its relation to the natural laws, the essence of the physical universe and its evolution in time.

 

 

CC

[Pyrotex]

A little side-note on the above (and fascinating) debate between metabolism vs replication first:

 

Metabolism was first. However, RNA was a waste-product.

 

RNA was a waste-product that stored information that reflected the metabolism process. Each step of metabolism produced an amino acid and a sugar molecule as wastes. Like those long strings of feces you see trailing from your pet goldfish, RNA trailed from the metabolic reaction, and eventually interferred with or "poisoned" that reaction.

 

It was a short bio-chemical twist of evolution from RNA as record of past actions, to RNA as template for operation--and then template for reproduction.

 

Information is like energy. It can drive reactions.

 

[EDIT] As far as I know, this theory is mine. I do not recall reading this any where else.

Nelson Thompson

[VladimirMatveev]

Vladimir Matveev. The great basic question of science: Membrane compartment or non-membrane phase compartment is a physical basis for origin of life?

Oral presentation at The 2nd All-Russian Conference on Astrobiology. Moscow, Pushchino, 5-9 June 2016. 

Video in English: https://youtu.be/Hn7A-1w0tuQ

 

Presentation slides in English as pdf:

http://www.bioparadigma.spb.ru/conf/Matveev-2016-The.great.basic.question.of.science_Eng_Slides.pdf

 

Comments for slides in English: 

http://www.bioparadigma.spb.ru/conf/Matveev-2016-The.great.basic.question.of.science_Comments_Eng.pdf

[Moontanman]

 

Vladimir Matveev. The great basic question of science: Membrane compartment or non-membrane phase compartment is a physical basis for origin of life?

Oral presentation at The 2nd All-Russian Conference on Astrobiology. Moscow, Pushchino, 5-9 June 2016. 

Video in English: https://youtu.be/Hn7A-1w0tuQ

 

Presentation slides in English as pdf:

http://www.bioparadigma.spb.ru/conf/Matveev-2016-The.great.basic.question.of.science_Eng_Slides.pdf

 

Comments for slides in English: 

http://www.bioparadigma.spb.ru/conf/Matveev-2016-The.great.basic.question.of.science_Comments_Eng.pdf

 

 

 

I'll do my best to discuss this after I've watched your video a couple more times. First blush on this is very positive.. 

[Moontanman]

 

Vladimir Matveev. The great basic question of science: Membrane compartment or non-membrane phase compartment is a physical basis for origin of life?

Oral presentation at The 2nd All-Russian Conference on Astrobiology. Moscow, Pushchino, 5-9 June 2016. 

Video in English: https://youtu.be/Hn7A-1w0tuQ

 

Presentation slides in English as pdf:

http://www.bioparadigma.spb.ru/conf/Matveev-2016-The.great.basic.question.of.science_Eng_Slides.pdf

 

Comments for slides in English: 

http://www.bioparadigma.spb.ru/conf/Matveev-2016-The.great.basic.question.of.science_Comments_Eng.pdf

 

 

 

Are you familiar with Dr. Jack W. Szostak's work?  

[VladimirMatveev]

Are you familiar with Dr. Jack W. Szostak's work?  

 

He works with a membrane model (see link below). Such experiments could be replicated with bulk phase models (like Fox's microspheres). In this case, the results could have been even more impressive. Unfortunately lipid membrane limits an imagination of scientists. 

http://exploringorigins.org/protocells.html

Edited August 9, 2016 by VladimirMatveev