Abiogenesis discussion

[syzygy42]

Hmm .. not that it matters so much for this chit-chat, I believe there are 500 or so, naturally occuring amino acids. Of these, ~240 occur 'freely' in nature, (unbounded by proteins, where proteins are themselves, the end products of biosynthetic pathways). 20 are coded for by the Standard Genetic Code (with extra 2 'oddballs', as well).

One of the basic questions is why these 20? Why not more? The code is also optimized to minimize the effect of mutations on the function of a protein. Third base changes generally do not change the amino acid, and when they do it is usually on with the same chemical properties of the side chain. No one that I know of has put forth a compelling scenario for the evolution of the code.

Amino acids show up every where in metabolism, both D- and L-forms. A quick perusal of a few biosynthetic pathways will reveal that there are many more amino acids that are intermediates in the synthesis of the canonical 20. Why were any one of those not selected to be coded into protein? Perhaps some of them were, e.g., ornithine is an intermediate in arginine synthesis and could have filled a role for a basic amino acid in primitive proteins.

... and they've managed to sythesise ribosomes from scratch ! (Well, technically speaking its called 'bio-engineering' which capitalises on the flow-on benefits of DNA sequencing research, and a whole bunch of clever equipment).

Actually, I ran across a paper that is really stunning. Michael Yarus's lab found a 5 nucleotide RNA that could take an activated amino acid (Phe-AMP, Phe-UMP, or Met-AMP) and catalyze the transfer of the amino acid onto the 2'-OH of a partially complementary RNA. The sequence of the RNAs are GUGGC (the ribozyme) and GCCU (the substrate). What really blows me away is that further amino acids could be added to form short polypeptides on the end of the GCCU substrate.

Of course, this is only a small step and is somewhat artificial: the activated Phe-AMP was present at 1-2 mM, but just demonstrating this really, really simple reaction is important in discovering other interesting catalytic possibilities. Many of the ribozymes that have been discovered are much larger, though this may just be a byproduct of the methods used to make and select the molecules. Most methods I've seen are derived from the SELEX method of generating RNA aptamers.

Hmm .. well, clearly metabolism is essential. Heritability and replication are also essential. Whilst these latter two, clearly require metabolism, they are separable functions which also make use of the same cell componentry.

Certainly, classifying the functions of different components is a powerful way of organizing the processes of a cell, but at their core heritability and replication are a series of reactions in which one component meets another and something happens. One pitfall is to inappropriately assign a limiting definition of a function to a molecule or class of molecules. A prime example is the thought that only proteins were catalysts. Once RNA was show to perform catalysis, people started noticing that it was not an inert carrier of genetic information or a structural component of the ribosome.

I guess the point that I was trying to make was in thinking about prebiotic and early evolution, we have to be careful not to limit ourselves by the admittedly successful conceptual framework built around our knowledge of how cells function. In a self-sustaining system, every component is required for its own synthesis, be they intermediates in a metabolic pathway or a complex structure such as RNA polymerase. Coming to grips with the structure of biological networks is a challenge.

Finally, here is a fabulous lecture about the ribosome.

Cheers

[Paul Wally]

Certainly, classifying the functions of different components is a powerful way of organizing the processes of a cell, but at their core heritability and replication are a series of reactions in which one component meets another and something happens. One pitfall is to inappropriately assign a limiting definition of a function to a molecule or class of molecules. A prime example is the thought that only proteins were catalysts. Once RNA was show to perform catalysis, people started noticing that it was not an inert carrier of genetic information or a structural component of the ribosome.

I guess the point that I was trying to make was in thinking about prebiotic and early evolution, we have to be careful not to limit ourselves by the admittedly successful conceptual framework built around our knowledge of how cells function. In a self-sustaining system, every component is required for its own synthesis, be they intermediates in a metabolic pathway or a complex structure such as RNA polymerase. Coming to grips with the structure of biological networks is a challenge.

I'm beginning to think that it's not as simple as saying that anything we can observe in present cell chemistry came first, or before everything else. Perhaps we should look at it as the evolution of a whole chemical system over time, i.e. from one whole to the next whole, instead of this whole evolving from parts identifiable within this whole. Consider for instance what we may identify in current cell chemistry as a "component" e.g. a particular catalyst: What if this catalyst is simply the stable unchanging part of the chemical system, i.e. it exists in some kind of dynamic equilibrium with a whole chemical network?

[syzygy42]

I'm beginning to think that it's not as simple as saying that anything we can observe in present cell chemistry came first, or before everything else.

Paul,

I certainly agree with you here. Saying something came first, implies a first cause, a notion that brings several millennia worth of philosophical baggage -- turtles all the way down. I certainly favor models that postulate a coevolutionary development of specific subsystems within a larger framework. I especially dislike the strong/pure RNA world model, mostly because it also postulates that replicating RNA molecules also could catalyze the metabolism required to synthesize themselves. RNA can do amazing things but being a universal catalyst is not one of them. Nevertheless, there are some very good workers exploring the function space of RNA, and their results may have relevance even if they do not directly lead to a better understanding of abiogenesis. For me, I like to keep the edges of my models fuzzy so that I won't reject an idea purely on the basis of some strong philosophical position.

Perhaps we should look at it as the evolution of a whole chemical system over time, i.e. from one whole to the next whole.

I could not have said it any better. Trying to grok the structure and properties of such an evolvable system has been a pursuit of mine ever since I entered the world of biological research.

Consider for instance what we may identify in current cell chemistry as a "component" e.g. a particular catalyst: What if this catalyst is simply the stable unchanging part of the chemical system, i.e. it exists in some kind of dynamic equilibrium with a whole chemical network?

This cuts to the core. I could tell you what I think and link several papers on the subject, but I would rather hear how you arrived at this notion.

[Paul Wally]

Consider for instance what we may identify in current cell chemistry as a "component" e.g. a particular catalyst: What if this catalyst is simply the stable unchanging part of the chemical system, i.e. it exists in some kind of dynamic equilibrium with a whole chemical network?

This cuts to the core. I could tell you what I think and link several papers on the subject, but I would rather hear how you arrived at this notion.

Well, I noticed that your thinking lead in the direction of mutual inter-dependence, which leads to wholism: The whole depends on the part and the part depends on the whole i.e. mutual inter-dependence between part and whole. I read up a lot on emergence and wholism, so it's difficult to trace back to any particular reference.
I do remember reading a paper by Paul Humphreys (2008), Synchronic and Diachronic emergence, for a more general reason than biology. The concept that stood out for me there was "recirculating autonomy". Here's a quote from Humphreys' paper:

In the first kind, the macro-structure is stable under dynamic micro-processes involving the
same constituents over time. We can call this recirculating autonomy.

For me this is an example of dynamic equilibrium. I'm not sure, however, whether the same concept can be applied to cell biochemistry. For instance how would we tell the difference between a molecule that is in dynamic equilibrium with it's chemical environment and one that exists independently?

[syzygy42]

I do remember reading a paper by Paul Humphreys (2008), Synchronic and Diachronic emergence

Interesting reference -- A whole branch of systems/complexity theory that I was not aware of. I don't have access to the full paper, but there is at least a superficial similarity to Robert Rosen's work. What Rosen called replication, renamed organizational invariance by Cornish-Bowden, is a property of a system that can maintain its catalytic structure by replacing components lost to dilution or degradation. As I outlined in the other thread, there are many other systems that contain the same underlying thought. Over the years, I have run into conceptually similar thoughts permeating many other areas of study: economics, ecology, and engineering (of all types) along with some of the well known physics/math related subjects pioneered by Godel, von Neumann, Shannon, Turing, etc.

For me this is an example of dynamic equilibrium. I'm not sure, however, whether the same concept can be applied to cell biochemistry. For instance how would we tell the difference between a molecule that is in dynamic equilibrium with it's chemical environment and one that exists independently?

Such a thought has been around for a while. The old term is homeostasis, the ability of an organism to maintain a stable inner environment, far from equilibrium. The problem faced by biologists in trying to develop a comprehensive theory was that there was little knowledge of the components of the systems under study. One could detect that there was a system controlling for example the rate of consumption of glucose (this goes back to Pasteur), but how it was achieved was entirely speculative. Things changed with the development of modern biochemistry and genetics following Watson & Crick and Jacob & Monod among many others.

Armed with good maps of the molecular landscape along with an ever growing molecular and computational toolkit, biologists are now able to directly test some ideas that have been kicking around for decades. As you might expect, new analysis challenges some of the old, well established models that couldn't be tested when they were proposed. For example, end-product feedback regulation of the first committed enzymatic step in a pathway was thought to be the mechanism by which the flux along a metabolic pathway was controlled. It made sense: high amount of product would inhibit an enzyme early in its pathway, reducing the flux until the concentration of the end-product dropped. The prediction was that mutating the regulated enzyme so that it was no longer subject to feedback inhibition would increase the flux through the pathway and result in excess production of the end-product. Although some pathways worked that way, many did not, much to the frustration of the metabolic engineers. It turns out that the control of flux is often distributed along the whole pathway and the state of the whole system. Huh? Who ordered that?

One early success of a theoretical approach was the use of modelling and numerical simulation to explain how bacterial chemotaxis works. Bacteria can detect a concentration gradient and swim either up the gradient to higher attractant (sugars, amino acids) concentrations or down a gradient to avoid nasty stuff. Considering bacteria are only ~1 micrometer in length, it's a pretty good trick. One sort of general theme that has emerged is that flux along a metabolic pathway or transmission along a signalling pathway is highly variable. Rather that having a dynamic equilibrium or steady state, the cell is a noisy environment. There is a strong argument that a certain amount of noise is required for a system to properly function.

Things are still in their infancy. We are just catching glimpses of these systems in action. Besides abiogenesis, I am interested in how metabolic and regulatory networks evolve.

Cheers

[publiusr]

Rather than having a dynamic equilibrium or steady state, the cell is a noisy environment. There is a strong argument that a certain amount of noise is required for a system to properly function.

I seem to remember someone talking about brownian motion playing a part.

This is what makes me a bit skeptical (O/T) of independant nanotech. Imagine a mosh pit where a singer is being chased by two '"squares." Our hero dives from the stage, lands atop his admirers and gets pushed hand over hand to a doorway to make his escape. Things work out best when there was no direction.

The two 'square's are nanites.

"The shortest path between two points is a straight line--I'm here..the doorway of my prey is there, so I'll just go straight--ow, quit pushing! umph--hey, how'd I get backed into this corner?"

Life processes do well without trying. Be too goal oriented--and get stifled. Also, the more complicated something is, the more vulnerable. A zygote can become an aerospace engineer in 20-30 years, but literally has to be babied into existence at the micro and macro levels--umbilicals, etc. Place a zygote on the ground--and it dies.

Radiodurans is tough. it makes another radiodurens, and they both sit there and do little to nothing. The more you overthink the plumbing...