The Origin of Biochemical Chirality

[John Hewitt]

Biochemical chirality is the fact that living things are made mainly from left or right handed molecules but, generally, not both. For example, proteins use L-amino acids and only a few D amino acids are found in nature.

The origin of this chiral specificity is now recognized as a very perplexing problem for biology and for our ideas about evolution and the origin of life.
As many readers will know, I have my own views on some of these matters - bioepistemic evolution.

I argue that all evolution is a data process and that all evolutionary theory should be based upon the concept of data. Therefore, I argue, it is not correct to regard genes as central to evolution and that genes merely format some of the data in DNA. Among other things, I have applied this evolutionary approach to abiogenesis, the origin of life and the emergence of metabolism.

Over the past year or so I have been extending this approach by addressing the problem of chirality. I have now made that study available on the internet. People interested in the problem are referred to

http://www.sexandphilosophy.co.uk/pe20_evolution_chirality.htm

Readers are especially referred to the section on metabolic bistability. In my view, this "metabolic bistable" idea is the best approach to the problem of chirality. I may add that my discussion seems to be the first time such ideas have been applied to the chirality problem.

I would be interested in what people think.

 

[BenBurch]

Ummm...

Actually the biologists I know chalk it up to random chance and nothing more.

 

[The Man]

I argue that all evolution is a data process and that all evolutionary theory should be based upon the concept of data. Therefore, I argue, it is not correct to regard genes as central to evolution and that genes merely format some of the data in DNA. Among other things, I have applied this evolutionary approach to abiogenesis, the origin of life and the emergence of metabolism.

So is the other data, not formatted into genes, not formatted at all or formatted in some other configuration?

 

[Graham Jackman]

Much speculation , little evidence. However rare chiral rocks may be, they seem a much more likely explanation than an asymmetry in chemical reactivity of isomeric forms in an achiral medium

 

[John Hewitt]

Much speculation , little evidence. However rare chiral rocks may be, they seem a much more likely explanation than an asymmetry in chemical reactivity of isomeric forms in an achiral medium

"Much speculation, little evidence" fairly describes the field as a whole, not particularly my work. Its applicability is probably inevitable. In my judgment, achiral rocks are too rare to have influenced events.

It is a definite fact that bistable circuits can be made in electronics that are physically symmetrical but which enter an asymmetric state when powered. Another fact is that bistable behaviour is known in existing metabolic systems.

My point is that it does seem possible to construct analogous bistable circuitry using the metabolic pathways of amino acid metabolism. Many of the necessary enzymes are known so the theory seems reasonable to me.

 

[John Hewitt]

So is the other data, not formatted into genes, not formatted at all or formatted in some other configuration?

Formatted in other configurations.

In reply to Ben Burch, most biologists do regard this issue as a problem and there is a large literature on it.

 

[Graham Jackman]

"Much speculation, little evidence" fairly describes the field as a whole, not particularly my work. Its applicability is probably inevitable. In my judgment, achiral rocks are too rare to have influenced events.

It is a definite fact that bistable circuits can be made in electronics that are physically symmetrical but which enter an asymmetric state when powered. Another fact is that bistable behaviour is known in existing metabolic systems.

My point is that it does seem possible to construct analogous bistable circuitry using the metabolic pathways of amino acid metabolism. Many of the necessary enzymes are known so the theory seems reasonable to me.

Electronic bistables are not chiral. Your examples of enzymes reqwuires that quite complex structures had evolved before chirality ensued. I could see this producing a local effect, but on average you'd expect a population of chiral pairs, rather than a single chiral form. I await evidence.

 

[MRC_Hans]

It is a definite fact that bistable circuits can be made in electronics that are physically symmetrical but which enter an asymmetric state when powered. Another fact is that bistable behaviour is known in existing metabolic systems.

Apart from being irrelevant, it is also incorrect. The definite fact is that it is impossible to make a bistable electronic circuit that is entirely symmetrical. Even if we assume ideal components (which do, of course, not exist in the real world), there will be an asymmetry on the quantum level on start-up.

.... Interestingly, if you use circuit simulation programs, a symmetrical bistable will not enter an assymetrical state when powered (unless you have programmed in a noise source).

Now for chirality: The fact that researchers call it a "problem" does not mean that it in any way jeopardizes the main theories (of evolution and abiogenesis). In the scientific world, a "problem" is something that still lacks a definitive explanation, and is thus still open for research and theorizing. Since chirality is probably required for proteines to function, it is probably a result of early evolution; the proto-organisms that did not have chirality were most likely selected against.

Hans

 

[The Man]

Formatted in other configurations.

In reply to Ben Burch, most biologists do regard this issue as a problem and there is a large literature on it.

What is the foamat of these other configurations?

 

[John Hewitt]

Electronic bistables are not chiral. Your examples of enzymes reqwuires that quite complex structures had evolved before chirality ensued. I could see this producing a local effect, but on average you'd expect a population of chiral pairs, rather than a single chiral form. I await evidence.

I don't understand the relevance of your first sentence. As I said, electronic bistables can be physically symmetrical, which is another way of saying they are not necessarily chiral.
I have previously shown how metabolic pathways could have emerged by evolution of chemical oscillations. Within this view, chiral specificity emerged from their further evolution. I expect the earliest evolution of amino acid pathways would have had parallel, L and D, enantiomeric pathways and I would argue that chirality emerged by the emergence of crossover inihibition that would cause one of those pathways to be switched off by the other. In other words, yes, I do think that chirality emerged within an existing evolutionary process and from structures that were, as you say, already quite complex.
A bistable switches one channel of its circuit on and the other off. The theory makes the mirror image, L and D, metabolisms into the two channels and thus requires that either the L or the D enantiomeric metabolism will remain switched on and the other will be switched off. This seems consistent with the facts. Modern organisms emerged from within the pathway that stayed switched on, which will have been L amino acids.

 

[John Hewitt]

What is the foamat of these other configurations?

You should read the bioepistemic evolution link on "sex and philosophy." Bioepistemic evolution is an example of a multilevel selection scheme which defines its levels according to the location of the selective process.
The levels are
Level0, prebiotic evolution
Level1, evolution based on DNA sequence
Level2, selection of sensory information
Level3, selection of deliberately transmitted information within the receiving organism of a social group.
Level4 is irrelevant for evolutionary biology.

 

[John Hewitt]

Apart from being irrelevant, it is also incorrect.

No, it is correct and this is just school level physics.

The definite fact is that it is impossible to make a bistable electronic circuit that is entirely symmetrical. Even if we assume ideal components (which do, of course, not exist in the real world), there will be an asymmetry on the quantum level on start-up.

.... Interestingly, if you use circuit simulation programs, a symmetrical bistable will not enter an assymetrical state when powered (unless you have programmed in a noise source).

This seems to be pedantry.

Now for chirality: The fact that researchers call it a "problem" does not mean that it in any way jeopardizes the main theories (of evolution and abiogenesis). In the scientific world, a "problem" is something that still lacks a definitive explanation, and is thus still open for research and theorizing. Since chirality is probably required for proteines to function, it is probably a result of early evolution; the proto-organisms that did not have chirality were most likely selected against.

My work is not affected by whether people call this topic a "problem" or a "difficulty." My aim has been simply to accommodate the origin of chiral specificity into the overall scheme of "the evolution of prebiotic oscillations." I begin with metabolic pathways since that theory offers an understanding of their origin.
I see no similar foundation for the claims you have made.

 

[tracer]

For example, proteins use L-amino acids and only a few D amino acids are found in nature.

When Miller and Urey did their experiment, where they created amino acids out of what they thought (at the time) was the primordial atmosphere of the Earth by simple electrical jolts, what kinds of amino acids were formed?

Did the experiment (A) form mostly L amino acids, (B) form mostly D amino acids, or (C) form L and D amino acids in roughly the same proportions?

If the answer is (A), that's the reason right there. No need to load any information theory on top of it.

 

[MRC_Hans]

No, it is correct and this is just school level physics.

This seems to be pedantry.

Unfortunately, it is the kind of pedantry that shows you to be wrong.

My work is not affected by whether people call this topic a "problem" or a "difficulty." My aim has been simply to accommodate the origin of chiral specificity into the overall scheme of "the evolution of prebiotic oscillations." I begin with metabolic pathways since that theory offers an understanding of their origin.

Perhaps not, but it is pertinent to the relevance of your work. If chirality was a fatal problem for evolution, then developing a theory to encompass it would be important, but if it isn't, then building some complex theory on top of the existing evolution theory is unparsimonious.

Hans

 

[John Hewitt]

When Miller and Urey did their experiment, where they created amino acids out of what they thought (at the time) was the primordial atmosphere of the Earth by simple electrical jolts, what kinds of amino acids were formed?

Did the experiment (A) form mostly L amino acids, (B) form mostly D amino acids, or (C) form L and D amino acids in roughly the same proportions?

If the answer is (A), that's the reason right there. No need to load any information theory on top of it.

Under normal circumstances, all chemical reactions that produce chiral compounds produce them as racemic mixtures, that is to say, as an exactly equal mixture of L and D isomers. That is what the Miller Urey experiment did. No large enantiomeric excesses have been found to result from any plausible physical process.

The same result is what is found in most interstellar sources of "organic compounds." In a few cases, most notably the Murchison meteorite, an enatiomeric excess of the L form is claimed by some workers. Others have failed to confirm that observation and have ascribed the reported results to contamination from biological sources during impact with earth or during sample handling. In any case, the claimed excess is of the order of 2-3% which, in my view, would not be sufficient to overcome the racemization processes that would be present on earth.

 

[John Hewitt]

Unfortunately, it is the kind of pedantry that shows you to be wrong.

I would be grateful if, rather than simply asserting that you believe my work to be incorrect, you would explain how you come to that conclusion and in what particulars you believe it to be in error.
One school book that discussed bistable circuits was Tom Duncan's A level physics book from 1982. You might note that one does not need to think about quantum asymmetry or variation in the properties of transistors in order to understand the workings of such devices.

Perhaps not, but it is pertinent to the relevance of your work. If chirality was a fatal problem for evolution, then developing a theory to encompass it would be important, but if it isn't, then building some complex theory on top of the existing evolution theory is unparsimonious.

Hans

My most recent study is intended to present an interpretation of chiral specificity, the molecular mirror asymmetry, that is seen in biology. The fact of that specificity is beyond any dispute.
I develop my interpretation from within the context of my own previous work, namely bioepistemic evolution (evolution based upon data not genes) and the evolution of prebiotic oscillations which is, itself, a theory of abiogenesis derived from bioepistemic evolution.
My work is, therefore, evolutionary in character and I fail to see why you describe it as a challenge to "evolution." It is true that there are popular approaches to evolutionary theory with which I disagree, notably the "gene-centred" approach popularized by Dawkins and the "replicator" approach to abiogenesis and evolution in general.
I consider those notions to lack any serious theoretical foundation. One of my primary aims is to identify phenomena which have not been interpretable in terms of these popular ideas and develop interpretations in terms of bioepistemic evolution.
The observed phenomena upon which I have focused so far have been
1. Human sexuality
2. Humour
3. Abiogenesis
4. Chiral specificity

In each case, no satisfactory "gene-centred" interpretation has been developed but, in each case, bioepistemic evolution has been able to do so. What that tells me is that conventional evolutionary theory is incorrectly formulated.

 

[blutoski]

I think my major criticism with the paper is that in 7.3 you dismiss what is in most people's opinion a very satisfactory model. This leads to your 'metabolism first' assumptions.



I think the problem is that you're focusing on amino acids, but at this point, it's pretty much consensus that AA was a late development in precellular life. The most primitive enzymes in cells are made of RNA. The most primitive enzymes - a sort of biochemical archaeology - suggest that replication predates metabolism.

Having said that, while I understand the bistable circuit metaphor, I confess I had trouble understanding how it mapped to chemical pathways. Are you suggesting that the L pathways evolved to create chemical outputs that blocked D pathway active sites (or disassembled D pathway components), and vice-versa, until one was completely shut down and the line exterminated?

If so, then... sure: why not?




I do have a question about these enzymes that are 'not made on ribosomes'. What does this mean - how are they assembled?

 

[anor277]

Under normal circumstances, all chemical reactions that produce chiral compounds produce them as racemic mixtures, that is to say, as an exactly equal mixture of L and D isomers. That is what the Miller Urey experiment did. No large enantiomeric excesses have been found to result from any plausible physical process.

............

There are in fact a few examples of spontaneous generation of chirality during a physical process. The best example, now classic, is the crystallization of certain binaphthyls whose enantiomers could be interchanged in solution. In certain circumstances, the first (chiral!) crystal provided a template for the homochiral crystallization of the rest of the batch. From memory, repeated recrystallizations gave a range of ee's in the shape of a Gaussian. If you want it, I will try to dig out the reference.

 

[John Hewitt]

I think my major criticism with the paper is that in 7.3 you dismiss what is in most people's opinion a very satisfactory model. This leads to your 'metabolism first' assumptions.

Section 7.3 was rather brief because I had already reviewed origin of life theories elsewhere. I am think you are referring to the RNA world theory as the idea that most people find satisfactory. I don't understand why they find it satisfactory because, so it seems to me, the RNA world theory presents a bigger chirality problem than do amino acids. Of the 20 standard amino acids, 18 have only one chiral centre - threonine and isoleucine being the exceptions. So, for most of the amino acids, there are only two isomers to worry about. By contrast, pentose sugars like ribose have three chiral centres. Hence, to build an enzyme from ribose you must solve this same problem three times over.

So, the amino acids seem to offer a simpler approach.

I think the problem is that you're focusing on amino acids, but at this point, it's pretty much consensus that AA was a late development in precellular life. The most primitive enzymes in cells are made of RNA. The most primitive enzymes - a sort of biochemical archaeology - suggest that replication predates metabolism.

It is true that those are the claims made by advocates of the RNA world theory but I do not think there is any genuine evidence to support them. RNA is a very labile molecule and offers a much narrower range of potential enzymatic activities than does RNA. I understand, for example, that RNA has not yet been shown to catalyze any redox reaction. This is disquieting since redox reactions underlie the energy producing activities of cells.

Having said that, while I understand the bistable circuit metaphor, I confess I had trouble understanding how it mapped to chemical pathways. Are you suggesting that the L pathways evolved to create chemical outputs that blocked D pathway active sites (or disassembled D pathway components), and vice-versa, until one was completely shut down and the line exterminated?

If so, then... sure: why not?

Yes I am saying that. In fact I am saying that, since the L and D pathways were competitive, each with have evolved to create products that blocked the other by channeling material back into the achiral pool. Those activities would have produced the cross-inhibition that converted these pathways into an evolutionary bistable. Over the generations one would be left with one, but at most remnants of the other. It is notable that D-amino acid dehydrogenase, an enzyme that would have a cross-inhibitory effect in such a system, exhibits its activity against almost all the D amino acids, not just one or two of them. This is what I would expect.

I do have a question about these enzymes that are 'not made on ribosomes'. What does this mean - how are they assembled?

I am not too sure which enzymes you are referring to. Amino acids can come together to form peptides under some conditions. According to my work, the initial synthesis of catalysts would be on oily droplets but would be powered by temperature cycling as with other oscillations.

If you mean the peptide antibiotics or the peptidoglycans of the bacterial cell wall, then these exist today. Their metabolic pathways are understood and do not involve ribosomes. I would interpret those pathways as hangovers from the time before data storage processes had evolved. It is notable that they do involve D amino acids.

 

[John Hewitt]

There are in fact a few examples of spontaneous generation of chirality during a physical process. The best example, now classic, is the crystallization of certain binaphthyls whose enantiomers could be interchanged in solution. In certain circumstances, the first (chiral!) crystal provided a template for the homochiral crystallization of the rest of the batch. From memory, repeated recrystallizations gave a range of ee's in the shape of a Gaussian. If you want it, I will try to dig out the reference.

Yes, as you say, there are a few examples of chiral separation being demonstrable but those are quite unusual circumstances and I don't think they apply to biochemical chirality.
I have come across the "lockwasher" structures that come about with the polyaromatics but I didn't think that was a crystallization process; rather, I thought that each molecule was either the L or D structure and that they didn't interchange. That's only a vague recollection and I am probably wrong. I would be interested in the paper.