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An encounter with a critic of biological semiosis

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RoyalSociety3

For those who are unfamiliar with The Royal Society, it’s an academic organization whose membership includes many of the world’s most eminent scientists, and is “the oldest scientific academy in continuous existence”. In loose terms, they are a British forbearer to many of the various Academies of Science sprinkled throughout the nations of the world. From their mission statement:

The Society’s fundamental purpose, reflected in its founding Charters of the 1660s, is to recognize, promote, and support excellence in science and to encourage the development and use of science for the benefit of humanity.

This article isn’t necessarily about the Royal Society, except for the fact that it serves as the genesis of the story, and also a proper backdrop to frame the issues at hand.

What is at issue is the void that seems to exist between the average working biologist and the fundamental reality that DNA (the genome) is a genuine representational medium. It operates in a system that translates the representations it uses to encode biological information into long-term memory. It is not sort-of-like information; it is not kind-of-like information. From a physics perspective, it functions exactly like the words you are reading right now. In fact — again from a physical systems perspective — only genetic encoding can match the variety and open-ended content of the words on this page. The genetic code and recorded language are the only two physical systems like this in the entire cosmos. They use spatially-oriented representations and a reading-frame code. It is the organization of arbitrary constraints that enables the combinatorial encoding of effects. In the total sum of human knowledge, they are a set of two    – with no others.

Royal-Society-March-2016

In their March 2016 volume, the Philosophical Transactions of the Royal Society published a special collection of papers under the no-nonsense heading “DNA as Information”. The content of those papers reflect the fact that the study of information remains a huge subject in the sciences, with an array of research opportunities in every direction. Contributions among the twenty-odd papers in the collection include such topics as semantics, mathematics, physics, encoding, measurement, complexity, and the role of meaning in biology.

This issue of Philosophical Transactions is where this story begins. More specifically, it begins with a particular paper (presented in that collection) by a well-respected Italian professor and researcher, Marcello Barbieri, who has for many years promoted a paradigm shift to biological semiosis (biosemiosis) and who is currently advancing this effort under the moniker “Code Biology”.

In opening his paper, Dr Barbieri addresses the central issue of this article:

Molecular biology is based on two great discoveries: the first is that genes carry hereditary information in the form of linear sequences of nucleotides; the second is that in protein synthesis a sequence of nucleotides is translated into a sequence of amino acids, a process that amounts to a transfer of information from genes to proteins. These discoveries have shown that the information of genes and proteins is the specific linear order of their sequences. This is a clear definition of information and there is no doubt that it reflects an experimental reality. What is not clear, however, is the ontological status of information, and the result is that today we have two conflicting paradigms in biology. One is the ‘chemical paradigm’, the idea that ‘life is chemistry’, or, more precisely, that ‘life is an extremely complex form of chemistry’. The other is the ‘information paradigm’, the view that chemistry is not enough, that ‘life is chemistry plus information’.

A link to Marcello Barbieri’s abstract is available on the Royal Society website here.

We pick up the story on the reaction side of its publication; the reaction to these observations by an average American scientist — a published biologist — who voices his point of view on the World Wide Web.

In this article it will not be necessary to perform any critical review of the biologist’s comments; one can tell within just a few words the gist of his position. He clearly has no questions about the “life is chemistry” paradigm he was taught at his university, and he clearly finds any other suggestion to be simply absurd. In his critique of Barbieri’s paper, he begins on his left foot:

Critic: “The first thing that I need to point out is that the author is not a biologist. He is a semiotician (someone who studies symbols and meanings). This will readily explain some of his more idiotic claims …”

I entered the conversation to say that he was tremendously misinformed about Marcello Barbieri’s qualifications, and I posted a short passage of text copied from Barbieri’s webpage about his background. I was also little surprised by the complete disregard for the source of the publication itself – the world’s “oldest scientific academy in continuous existence”. Not only can Barbieri be ignored, but the Royal Society is publishing “idiotic claims” about biology – or so it seems.

code-biology-conf

But there is certainly more to this. I believe there are possibly three things at work in the reaction presented above. First and foremost are the material facts themselves; i.e. the observation of genuine representations and arbitrary constraints (formalized in memory) inside the cell are difficult things to explain by the physical properties of matter. After all, the very essence of genetic translation is that it systematically decouples the production of effects from sheer determinism (physicalism), making possible the full range effects necessary for biology to exist. In other words, a system that functions only by locally eliminating your favorite explanation is a difficult nut to crack.

Secondly, Barbieri’s paper was presented (in this particular instance) under the rubric of philosophy, which (as a general rule) is often looked down upon by certain classes of scientists. Not surprisingly, these often include those sciences (like evolutionary biology and theoretical physics) that promote the notion that they are answering mankind’s biggest questions. As I wrote on Biosemiosis.org, this is cavalier conduct in light of the actual evidence. In any case, for many people, the idea of systematic learning without philosophical grounding is a cart without a horse. The practice of systematic learning is itself a philosophy.

But thirdly, there is something even more central to this critic’s comments; he isolates the lowly “creationist” as the key figure in his response. They are, as it turns out, the real impetus for his comments. He begins “So, it seems that creationists have been spamming this article so I’ll analyze it”. By using the word creationists here, some might suggest the critic intends to attack only those who believe such things as the earth being six thousand years old, for instance. But I think we can fairly assume he intends to attack anyone who believes that life on earth is the product of a creation, and of course, anyone who could believe such a thing obviously deserves to be attacked. The mere appearance of the word provides sufficient license to trivialize both the observations being made, as well as any outfit that publishes them.

Now, I have no evidence one way or another that anyone or any group has piled on to Barbieri’s paper – and it makes not one ounce of difference either way. The real issue here is that verifiable physical evidence is being routinely belittled and ignored simply because it doesn’t conform to the personal metaphysics of proper-thinking biologists — and clearly this is about metaphysics. It’s about the treatment and teaching of metaphysics in science. While the self-appointed defenders of science posture about the provisional nature of science, make no mistake; no physical evidence is allowed to take root if it leads to the unimaginable proposition that today’s biologists could be wrong in their personal beliefs about ultimate reality.

And this view doesn’t merely exist among anonymous biologists posting on the web; it is the dominant view found throughout biology at all levels. For instance, Larry Moran is a respected Professor of Biochemistry at the University of Toronto, and has written multiple textbooks on the subject. But four and a half years ago, I asked him for a clear statement as to whether or not the genome (DNA) actually contained information. He replied:

In common parlance we refer to these sites as containing “information” in the form of specific nucleotide sequence. It’s a very useful analogy and I think everyone knows what we mean when we use it. Nobody expects it to conform to the meanings of “information” in other disciplines. Nobody, that is, except some IDiots who like to play semantic word games instead of addressing real science. I hope you’re not one of those people.

The problem with this, of course, is that investigator expectations are a secondary concern; the genome functions exactly like language, and vice versa.

In any case, the war on outcast metaphysics is made evident again and again. It’s a socio-political enterprise, and when it rises to the level of ignoring valid evidence, it becomes an enterprise aligned against reason itself. This critic of semiosis had no idea that semiosis was physically identifiable, and he doesn’t want to know.

–Upright BiPed

 


 

The remainder of my exchange with the critic follows below. What it lacks in debate it thankfully makes up for in brevity. The critic clearly threw in the towel, rather than show any interest in the science.

UB:  (posted Barbieri’s extensive background…)

– – – – – – – – – – – –

Critic:  Thank you for the correction. From the references that immediately jumped, he seemed to study biosemiotics. That’s very disappointing that he actually has conducted research because he is so wrong-headed in his article.

With regards to my name, I’m a published biologist. I’m a scientist and my name is Sam.

– – – – – – – – – – – –

UB:  Hi Sam. Good to know. Take care.

By the way, he is entirely correct in his paper, you are just unaware of the issues. It happens.

– – – – – – – – – – – –

Critic: No he isn’t. I gave very good reasons. This is far closer to my area of research than his.

– – – – – – – – – – – –

UB: Barbieri states that the code is not reducible to physics. He is correct. Like all code systems ever known to exist, the genetic translation system contains a natural (and necessary) discontinuity between the arrangement of the medium and the determination of its effect within the system. This local discontinuity is what makes it possible for a spatial arrangement of bases in a codon to specify a particular amino acid during synthesis. It is what establishes combinatorial permutations and enables open-ended heredity. I can appreciate the fact that this all sounds foreign to you, but that is only because you are unaware of the data – which has been documented in physics literature starting about half a century ago by physicists such as Howard Pattee and others.

– – – – – – – – – – – –

Critic: “Like all code systems ever known to exist, the genetic translation system contains a natural (and necessary) discontinuity between the arrangement of the medium and the determination of its effect within the system.”

There is no discontinuity. You must’ve never taken molecular biology.

“This local discontinuity is what makes it possible for a spatial arrangement of bases in a codon to specify a particular amino acid during synthesis.”

How so? This is just a bald assertion.

“It is what establishes  combinatorial permutations and enables open-ended heredity.”

Again, bald assertion.

“I can appreciate the fact that this all sounds foreign to you, but that is only because you are unaware of the data – which has been documented in physics literature starting about half a century ago by physicists such as Howard Pattee and others.”

How about you stop condescending to someone who wrote his Master’s thesis on the dynamics of the genetic code? Please make an argument rather than bald assertions you supercilious imbecile.

– – – – – – – – – – – –

UB: “There is no discontinuity.”

Like I said, the local discontinuity is an organizational necessity. The arrangement of bases in a codon does not determine which amino acid is presented for binding. I would think this should be obvious to someone of your training.

– – – – – – – – – – – –

Critic: “The arrangement of bases in a codon does not determine which amino acid is presented for binding.”

Strictly speaking, that is true, but there are a lot of contingencies built into the structure of the code. For example, we have the third base wobble. We also have the fact that more similar amino acids correspond to more similar codons. Thus, there seem to be contingencies built into the code. But, even if I grant you this, where does it get you in an argument?

– – – – – – – – – – – –

UB:  “where does it get you in an argument?”

This is one of the empirical markers a physicist would use to identify the organization of a semiotic code, i.e. the preservation of the discontinuity between the arrangement of the medium and the determination of its effect. The cell accomplishes this by isolating the establishment of the code from the reading of the codons, i.e. the amino acid-to-anticodon association is temporally and spatially isolated from the codon-to-anticodon association. This discontinuity is a physical necessity for translation to occur, and is evident in all instances of semiotic translation.

But that is just the first marker that a physicist would look for. There are others. For instance, genetic translation employs a reading frame code using combinatorial permutations. This requires the arrangement of the bases in each codon to be independent of the minimum total potential energy state of the medium. In other words, a pheromone (for instance) is an informational medium that is recognized in its system by its three-dimensional structure, and that structure is determined by its minimum total potential energy. But in order to enable combinatorial permutations, the arrangement of the medium must be independent of minimum total potential energy – which both DNA and RNA are. This is what physically enables the system to have the informational capacity it requires to describe itself into memory (i.e. to begin the cell cycle, and heredity). It is also what enables the efficient transcription of that high-content information from one medium to another.

These are the types of empirical observations that a physicist (like Pattee and others) would be acquainted with, as well as someone like Barbieri. Or John von Neuman. Or Francis Crick.

You are not acquainted with them, and it’s a sure bet they didn’t appear in your masters thesis on the dynamics of translation. No sweat. I am sure your thesis described other areas of interest in a competent manner. But when you step out and rant on areas of empirical findings that you are uninformed about, you make a mistake. In order to organize the heterogeneous cell, you must first be able to specify a thing and place it under temporal control. This is what protein synthesis does, and the translation of an informational medium is the means to accomplish that effect. But the translation of an informational medium requires one arrangement of matter to serve as a representational medium (codons), and another arrangement of matter to establish what is being represented (aaRS). After all, no object in the material universe inherent specifies any other object in the material universe. Nucleobases do not represent or specify amino acids. They have to be organized in a discontinuous translation system (i.e. semiosis) in order to do so. And that is exactly what is found inside the cell. The material observations that identify the system aren’t even controversial.

– – – – – – – – – – – –

Critic: Thanks for the tripe.

“This discontinuity is a physical necessity for translation to occur, and is evident in all instances of semiotic translation.”

The discontinuity isn’t a physical necessity. You could easily imagine a scenario where amino acids were necessarily assigned to anticodons by chemical properties of tRNAs. I’m sorry but if you can’t get that right, you’re pretty hopeless, idiotically pedantic, and a navel gazer. Goodbye.

– – – – – – – – – – – –

UB: In logic, that’s called “special pleading”. Your imagination, frankly, doesn’t mean diddly. It doesn’t provide you with any exemptions.

The minimum requirement for the origin of the system is established by what is physically necessary to record and translate the amount of information that the system needs to successfully describe itself into memory. On this front, there is very little room. A cell that cannot provide a record of itself cannot begin the cell cycle. A cell that cannot translate a record of itself also cannot begin the cell cycle.

To accomplish what must be accomplished, several of these individual associations (generous estimates typically run between 12 to 15) will need to occur at the same time and place, while the details of their construction are simultaneously encoded in the very information that they make possible.

Odd, isn’t it. Nature passed up on the fully determined (comparatively easy) associations lurking in your imagination, and instead (already faced with an almost vertical face to climb) picked an unnecessary system that preserves the discontinuity between the arrangements and their effects. And even odder still, every system of translation that has ever been examined has followed that same pattern.

Special pleading indeed.  Goodbye.

This article was posted from ComplexityCafe.com

Comments
And gpuccio, I can see that you're avoiding replying to me directly and instead addressing my points in your reply to others. Calling me names and attacking me personally won't make your moot points any more worthwhile. ///I am not a biochemist/// It shows, because you don't even understand molecular interactions. ///However, both the acceptor stem and the anticodon region are recognized by the aaRS because of their specific configuration, which depends on their sequence, which is different in different tRNAs. That’s what is called “code” in the paper linked by Evolve (and not understood by him)./// Codes or not, they involve molecular interactions, which you're adamantly denying. I don't know how many times I have had to correct this. For the umpteenth time, look at Figs: 1, 2 & 10 of Carter's review of his paper and read the relevant text: http://www.mdpi.com/2075-1729/5/1/294/htm There's a stereochemical relationship between bases in the RNA and amino acid residues. He calls it the stereochemical code. This results from physical interactions of these molecules. He talks about van der Waal's forces & hydrogen bonds. He even proposes that complimentary RNA-peptide hairpins can be formed by these interactions, which facilitate polymerization of both molecules. This, he speculates, can account for the origin of both RNA and short rudimentary proteins before the advent of modern genetics. ///They are two examples of artificial charging of tRNA by extremely artificail lab conditions, not certainly because the tRNA spontaneously reacts with the aminoacid./// http://www.sciencedirect.com/science/article/pii/0141813094900434 You're missing the crucial point here. This work shows that tRNAs can be specifically charged with the correct amino acid in the absence of aaRS. They use high pressure to simulate the conformational change normally induced by aaRS in the tRNA. And then the tRNA can specifically react with its "correct" amino acid even when the specific aaRS is absent! This means tRNA has the ability to select its "correct" amino acid if it is in the right conformation. And the role of aaRS is to induce the right conformational change in the tRNA. So much for your obstinate denial that tRNA cannot recognize its amino acid! In a follow-up paper, the same group further show that these pressure-charged aminoacyl tRNAs are indistinguishable from aaRS-charged ones in protein synthesis: http://onlinelibrary.wiley.com/doi/10.1080/15216549800202872/epdf They also discuss amino acid recognition by RNA molecules. ///The myths of primitive beings where aminoacids are spontaneously bound by tRNAs, and then spontaneously form peptides, without any transmission of information by DNA genes, and then by completely imprecise urzymes, so that in the end what we observe could evolve, are myths. Facts are all another thing./// Whether you like it or not, that's what a growing body of evidence is suggesting. Your biases will urge you to dismiss these as "myths", but they have emiprical support. Molecular interactions between RNA, amino acids and peptides fueled polymerization of both RNA and the first simple proteins. Later, proto-aaRS enzymes catalyzed addition of amino acids to proto-tRNAs, and protein synthesis was carried out on proto-ribosomes in the absence of any codon-anticodon pairing. This whole talk of "someone" having to invent a semiotic DNA translation system becomes superfluous.Evolve
March 23, 2016
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Evolve @146
If we had all the answers in step-by-step detail, we could have shut down our labs and gone home. We’re trying to figure out something that happened 3.5-4 billion years ago, that too molecular events which have hardly left any trace. It’s a daunting challenge.
Apparently you misunderstood my message:
Note this is not about speculating how it could have happened, but about describing in a comprehensive manner how it could be done, regardless of how it actually occurred.
Forget about natural history. Scientists have the biological systems right in front of their noses. They have the most advanced technology for researching. They have accumulated an enormous amount of information. I'm just asking to show me a valid accurate description of how to support what you wrote @143 that was quoted @145. That's all.Dionisio
March 23, 2016
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Dionso @ 133, //Only the answer to the 2nd question was correctly formatted Questions 1 throu 3 were “Yes”/”No” questions.// You never said upfront that your queries were only meant to be answered with a Yes or No. I only tried to enlighten you with some related info for each of your queries. But you reacted in an impolite fashion, quite unbecoming of a gentleman.Evolve
March 23, 2016
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If we had all the answers in step-by-step detail, we could have shut down our labs and gone home. We're trying to figure out something that happened 3.5-4 billion years ago, that too molecular events which have hardly left any trace. It's a daunting challenge.Evolve
March 23, 2016
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Evolve @143
...emerging evidence suggest that rudimentary peptide synthesis carried out by precursors of today’s aaRSs, tRNAs and ribosomes, originated before the DNA code was even involved in the process.
Then how could the current transcription-translation system* have arisen? Can you point to any serious literature that describes it accurately, step by step? Note this is not about speculating how it could have happened, but about describing in a comprehensive manner how it could be done, regardless of how it actually occurred. (*) including the post-transcriptional and post-translational modifications as well as other processes and mechanisms known to be part of the currently observed biological systems. Thank you.Dionisio
March 23, 2016
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///GP you are a rock star./// In name-calling and fact denials!Evolve
March 23, 2016
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///I do not say that/// You don’t say it, but you assume it. You’re talking teleologically as if the DNA code was first set and then a decoding system was established to decode it semiotically (by which you imply design). But emerging evidence suggest that rudimentary peptide synthesis carried out by precursors of today’s aaRSs, tRNAs and ribosomes, originated before the DNA code was even involved in the process. This, of course, is in line with evolutionary principles and predictions. ///On my website (Biosemiosis.org) I state that the aaRS satisfies a necessary systematic role that is found in all semiotic systems/// Teleology again. The aaRS’s role is not to establish any relationship with anything. It is the physical & chemical interactions that limit which amino acid can be bound by which aaRS and loaded on to which tRNA. Thus the amino acid a codon can code for is constrained by these interactions. There’s no freedom or choice here as in true semiotic systems. It’s governed entirely by spontaneous molecular interactions and the resulting limitations and constraints, something that doesn’t apply to man-made semiotic systems.Evolve
March 23, 2016
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Thank you GP, Dio, and Mung for commenting. GP you are a rock star.Upright BiPed
March 22, 2016
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UB and all others supporting him are wrong.
In case you haven’t noticed, Evolve, outside of a few kind (and obviously perceptive and brilliant) people who comment here on UD, I don’t have any active “supporters” – at least not in the established ID community, and certainly not in the semiotic community. I very thankfully have some friendly voices here and there, and that’s it. That is, of course, unless you are talking specifically about support for the demonstrated mechanics of genetic translation, then I have the whole world’s collective community of textbook authors on my side. Nice, isn’t it? :) More seriously Evolve, this isn’t about people, it’s about what can and cannot be demonstrated.
UB’s model is problematic on two counts: 1) He says that the codon does not determine the amino acid, it merely represents it.
On my website (Biosemiosis.org) I state that the aaRS satisfies a necessary systematic role that is found in all semiotic systems. That is; it is an arrangement of matter that “establishes the otherwise non-existent systematic relationship between the (codon) representation and its (amino acid) effect”. This is a demonstrated fact, repeated throughout the whole of biology. The set of aaRS systematically establishes the genetic code. That’s how the system works.
2) UB assumes that the present-day translation system (DNA-RNA-Protein) held true right from the beginning.
I do not say that, I say that semiosis has existed on earth at the point that the heterogeneous living cell became organized. I say this because semiosis is the physical means to organize it. - - - - - - - - - - - - (still reading)Upright BiPed
March 22, 2016
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WOW! I had no idea that this thread was still going. Let me catch up.Upright BiPed
March 22, 2016
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gpuccio Thank you for the excellent explanation (as usual).Dionisio
March 22, 2016
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Dionisio: The human genome has 497 identified tRNA genes. They differ both in the anticodon region and in the acceptor arm. However, the 3? end of all tRNAs have the sequence CCA, with the amino acid attached by the tRNA synthetase to the terminal adenosine residue.gpuccio
March 22, 2016
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Dionisio: I am not a biochemist, but I think that the answer to your question is: yes. The aminoacid binds by an ester bond to the 3'-OH group in the CCA end of the molecule, which is the same in all tRNAs, as far as I understand. The anticodon end, in particular, can have no real role in that binding, because it is at the other end of the tRNA molecule. The acceptor stem, instead, coould have some role in the biochemical interaction with the aaRS when the aminoacid charging takes place, because it's the acceptor stem which ends with the CCA sequence. However, both the acceptor stem and the anticodon region are recognized by the aaRS because of their specific configuration, which depends on their sequence, which is different in different tRNAs. That's what is called "code" in the paper linked by Evolve (and not understood by him). This acceptor stem code and anticodon code are not the same thing as the genetic code. They are the codes which implement the genetic code. The genetic code maps each codon of the DNA gene to an amonoacid. The acceptor stem code and the anticodon region code are sequences which are recognized by the specific aaRS. The combined recognition of both regions is symbolically coupled (by the aaRS structure) to the correct aminoacid, realizing so the implementation of the genetic code, because in the end the anticodon in the tRNA which is recognized by the aaRS corresponds symbolically to the aminoacid which is bound by the aaRS and then charged to the tRNA. It can be useful to remind, again, that no tRNA can biochemically discriminate between the aminoacids, least of all biochemically interact with its specific aminoacid. That simply does not happen. The two simple papers quoted by Evolve at #131 are further evidence of that. They are two examples of artificial charging of tRNA by extremely artificail lab conditions, not certainly because the tRNA spontaneously reacts with the aminoacid. For example, in the second paper, the abstract states:
This paper shows that the phenylalanine-specific tRNA of Escherichia coli as well as the yellow lupin methionine initiator tRNAMet can be charge specifically with phenylalanine and methionine, respectively, in the absence of specific aminoacyl-tRNA synthetases, under high pressure of a maximum of 6 kbar (1 bar = 105 Pa; 1atm = 1.01 × 105 Pa). The esterification reaction takes places at the 3? end of the tRNA molecules. The yield of Phe-tRNAPhe or Met-tRNAMet at high pressure is ?10 times lower than that of the enzymatic aminoacylation reaction. This reaction seems to be specific, and mis-aminoacylation of tRNAPhe and tRNAMet with serine is negligible. It is well known that tRNA undergoes conformational changes during interaction with an aminoacyl-tRNA synthetase. Similarly, on the basis of circular dichroism spectra, we showed that the conformation of tRNA at high pressure differs slightly from its original A-RNA form. Therefore, it can be speculated that the chargeable conformation of tRNA induced by the aminoacyl-tRNA synthetase during enzymatic aminoacylation and the one created at high pressure are similar and are most probably formed by a dehydration mechanism. We think that the ‘unique’ tertiary structure of tRNA existing under high pressure creates an active centre which might itself catalyse ester bond formation. Therefore, the structure of the amino acid stem of tRNA may determine (code) the charging of the particular amino acid to specific tRNA. This code is clearly distinct from the rules of the classical genetic code.
Emphasis mine. IOWs, it is true that the acceptor stem has a structure which is able to help the charging of the correct aminoacid, but in no way it can do it by itself. In the paper, they used extremely high pressures, up to 6 kbars, to change the structure of the tRNA in a way that allows the binding, a way which is similar to what the aaRS does. I quote again from the PDB page about these enzymes:
These enzymes are not gentle with tRNA molecules. The structure of glutaminyl-tRNA synthetase with its tRNA (entry 1gtr ) is a good example. The enzyme firmly grips the anticodon, spreading the three bases widely apart for better recognition. At the other end, the enzyme unpairs one base at the beginning of the chain, seen curving upward here, and kinks the long acceptor end of the chain into a tight hairpin, seen here curving downward. This places the 2' hydroxyl on the last nucleotide in the active site, where ATP and the amino acid (not present in this structure) are bound.
Emphasis mine. IOWs, the aaRS has a really central role: nothing could happen without it. a) It recognizes and binds the correct aminoacid and ATP, generating the aminoacyl-AMP. b)It recognizes the correct tRNA at two different sites, binds it and strongly changes its 3D structure (in a way which is similar to what we do with a pressure of 6 kbars). c) So, it charges the tRNA with the correct aminoacid, which corresponds to the anticodon in the tRNA according to the genetic code, and all that is done with an extremely low error rate. So, while Evolve continues to imagine tRNAs which spontaneously select their aminoacid, and shamelessly conflates bumping molecules with biochemical bindings, these are the facts. The myths of primitive beings where aminoacids are spontaneously bound by tRNAs, and then spontaneously form peptides, without any transmission of information by DNA genes, and then by completely imprecise urzymes, so that in the end what we observe could evolve, are myths. Facts are all another thing.gpuccio
March 22, 2016
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#133 error correction Part of the first sentence in the answer to the 3rd question was incorrectly stricken out. My fault.Dionisio
March 22, 2016
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gpuccio Thank you for the answers. Ensuring that I understood the situation implied by the answer to the second question, could any AA chemically bind -at least in theory- to the acceptor arm of any tRNA regardless of the tRNA anticodon loop, provided that some mechanism would bring the AA close to the tRNA acceptor arm? Regarding the 3rd question, here are two subquestions: 3.1) do the tRNA have the same acceptor arm? 3.2) is their main difference in the anticodon loop?Dionisio
March 22, 2016
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Dionisio: 1) Yes. 2) Yes. 3) Not only. The aaRS recognizes both the anticodon part and the acceptor stem part of the tRNA, which are at opposite ends of the molecule. 4) The aaRS recognizes its specific AA by a specific part of its molecule. Here is a good summary: "Aminoacylation must be carried out accurately: the correct amino acid must be attached to the correct tRNA if the rules of the genetic code are to be followed during protein synthesis. It appears that an aminoacyl-tRNA synthetase has high fidelity for its tRNA, the result of an extensive interaction between the two, covering some 25 nm2 of surface area and involving the acceptor arm and anticodon loop of the tRNA, as well as individual nucleotides in the D and T?C arms. The interaction between enzyme and amino acid is, of necessity, less extensive, amino acids being much smaller than tRNAs, and presents greater problems with regard to specificity because several pairs of amino acids are structurally similar. Errors do therefore occur, at a very low rate for most amino acids but possibly as frequently as one aminoacylation in 80 for difficult pairs such as isoleucine and valine. Most errors are corrected by the aminoacyl-tRNA synthetase itself, by an editing process that is distinct from aminoacylation, involving different contacts with the tRNA (Hale et al., 1997; Silvian et al., 1999)." An important point is that the process has to be very precise to be of any utility, because errors in translation can scarcely be tolerated. One of the problems with Carte's hypothesis of "urzymes" is that in no way they can ensure the needed precision and specificity. This is from Carter's review: "“Urzymes” are quite small, highly conserved fragments of the two aminoacyl-tRNA synthetase superfamilies (Figure 3). Our biochemical studies have shown that Urzymes from both classes retain ~60% of the Gibbs energies of catalytic proficiency of fully evolved synthetases [13,14,21] and ~20% of their specificities for amino acid activation" By the way, I think that I will not answer any more Evolve's "arguments". He is a fool, he does not understand, or simply he does not want to understand.gpuccio
March 22, 2016
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Evolve @131
///1. Does the “charging”/”loading” of a given tRNA(i) with a given AA(j) occur through the enzymatic catalyzing mediation of a given aaRS(k)?/// Yes, contemporarily. However, aaRS may not have been involved at the beginning. gpuccio posed me the question of how tRNAs can be charged without aaRS, at least without the ancestral urzyme version of aaRS. He hasn’t read enough. tRNAs have been charged with amino acids in the lab non-enzymatically: http://nass.oxfordjournals.org.....1/269.long http://www.sciencedirect.com/s.....3094900434
///2. Does the final “binding” of the given AA(j) to the given tRNA(i) take place at a part of the given tRNA(i) that is not specific to the given AA(j), i.e. it could “bind” a different AA(m) as well?/// Yes
///3. Is the association between the given aaRS(k) and the given tRNA(i) understood through the anticodon part of the given tRNA(i) which somehow is “recognized” by the given aaRS(k)?/// aaRS recognises both the acceptor stem of the tRNA (the part that binds to amino acid) as well as the anticodon end (the part that binds to the mRNA codon). But again, that’s with contemporary aaRSs. Ancestral versions of aaRSs have been reconstructed which were found to recognise only the acceptor stem. And ancestral versions of tRNAs have also been reconstructed that lack the anticodon part. These two facts gel well and collectively suggest that primitive translation involved no codon-anticodon pairing. That may have evolved only later.
///4. How is the given aaRS(k) associated to the given AA(j)? IOW, how does the given aaRS(k) “recognize” the given AA(j)? By some kind of unique structural features or physicochemical properties of the given AA(j)?/// aaRS binds the amino acid first, modifies it, then binds to the tRNA and attaches the modified amino acid onto the tRNA. But new studies are showing that the tRNA also sorts for amino acids based on their size, branching and polarity.
Only the answer to the 2nd question was correctly formatted. Questions 1 throu 3 were "Yes"/"No" questions, but in questions 1 and 3 you expanded your answers with hypothetical issues that were not requested by the question and could only add confusing noise to the answers. Actually, in question 3 the words "Yes" or "No" are missing. The 4th question is not a "Yes"/"No" question, but a "How?" question, hence it demands an explanation. That question was not answered at all or at least not explicitly. Please, note that I've emphasized the parts of the answers that met the required format and stroke out the parts that did not meet that requirement or were off the exact question focus. Please, try answering the 4th question again at your convenience, if you will. Thank you.Dionisio
March 22, 2016
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///Well, we humans establish the relationship between “car” and a car, so Mung is right/// He'll be right if we use an image of a car to represent a car (e.g., a traffic sign), because the image establishes the relationship. But the word "car" does not establish any relationship, it merely represents a car. ///BTW how about computer code? Is it a real code? Or is it reducible to molecular interactions?/// Computer code is of course a real code, but not involving chemistry in the same sense as codes in life, such as DNA. As such, analogies between the two don't hold water despite it being a favorite activity of creationists.Evolve
March 22, 2016
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///1. Does the “charging”/”loading” of a given tRNA(i) with a given AA(j) occur through the enzymatic catalyzing mediation of a given aaRS(k)?/// Yes, contemporarily. However, aaRS may not have been involved at the beginning. gpuccio posed me the question of how tRNAs can be charged without aaRS, at least without the ancestral urzyme version of aaRS. He hasn’t read enough. tRNAs have been charged with amino acids in the lab non-enzymatically: http://nass.oxfordjournals.org/content/48/1/269.long http://www.sciencedirect.com/science/article/pii/0141813094900434 ///2. Does the final “binding” of the given AA(j) to the given tRNA(i) take place at a part of the given tRNA(i) that is not specific to the given AA(j), i.e. it could “bind” a different AA(m) as well?/// Yes ///3. Is the association between the given aaRS(k) and the given tRNA(i) understood through the anticodon part of the given tRNA(i) which somehow is “recognized” by the given aaRS(k)?/// aaRS recognises both the acceptor stem of the tRNA (the part that binds to amino acid) as well as the anticodon end (the part that binds to the mRNA codon). But again, that’s with contemporary aaRSs. Ancestral versions of aaRSs have been reconstructed which were found to recognise only the acceptor stem. And ancestral versions of tRNAs have also been reconstructed that lack the anticodon part. These two facts gel well and collectively suggest that primitive translation involved no codon-anticodon pairing. That may have evolved only later. ///4. How is the given aaRS(k) associated to the given AA(j)? IOW, how does the given aaRS(k) “recognize” the given AA(j)? By some kind of unique structural features or physicochemical properties of the given AA(j)?/// aaRS binds the amino acid first, modifies it, then binds to the tRNA and attaches the modified amino acid onto the tRNA. But new studies are showing that the tRNA also sorts for amino acids based on their size, branching and polarity.Evolve
March 22, 2016
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UB and gpuccio Please help me with the 4 questions @128. Thank you.Dionisio
March 22, 2016
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Origenes @ 127
BTW how about computer code? Is it a real code? Or is it reducible to molecular interactions?
The code requires an OS for interpretation (which requires flow of electrons through the silicon chips) and once interpreted, at the hardware level again, electrons flow through the circuitary to interpret the code and drive the CPU, so computer code too requires, if not molecular - electron intercation :-)Me_Think
March 22, 2016
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This seems like an interesting discussion, but there are a few things I may not understand clearly: 1. Does the "charging"/"loading" of a given tRNA(i) with a given AA(j) occur through the enzymatic catalyzing mediation of a given aaRS(k)? 2. Does the final "binding" of the given AA(j) to the given tRNA(i) take place at a part of the given tRNA(i) that is not specific to the given AA(j), i.e. it could "bind" a different AA(m) as well? 3. Is the association between the given aaRS(k) and the given tRNA(i) understood through the anticodon part of the given tRNA(i) which somehow is "recognized" by the given aaRS(k)? 4. How is the given aaRS(k) associated to the given AA(j)? IOW, how does the given aaRS(k) "recognize" the given AA(j)? By some kind of unique structural features or physicochemical properties of the given AA(j)? Please, kindly forgive me if the above questions make no sense, are too 'dumb' or have been already answered in this thread. That would just confirm my deep ignorance on this subject. Thank you for any help with this.Dionisio
March 21, 2016
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Evolve,
Mung: There has to be something that establishes the relationship between the representation and that which is being represented. Without that you don’t have a semiotic system.
Evolve: Not necessarily. The word CAR does not relate to a car in any manner. It just so happens that we humans decided to represent a car with that 3-letter word in English.
Well, we humans establish the relationship between "car" and a car, so Mung is right. BTW how about computer code? Is it a real code? Or is it reducible to molecular interactions?Origenes
March 21, 2016
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gpuccio @112 & 113 You're all at sea here, gpuccio. The paper and the review DO talk about tRNA-amino acid interactions in spite of your vehement denials. I even cited a 1974 paper modeling RNA-amino acid interactions! By the way, I don't need lessons on aaRSs. You're forgetting that aaRSs are enzymes which can interact strongly or even form bonds with its substrates. But that does not mean tRNAs cannot interact with amino acids. They also interact, albeit at a weaker extent. It beats me why you can't get your head around this. First and foremost you must understand the difference between interaction and covalent bonding. A covalent bond is strong linkage where the two molecules involved are in very close proximity. Bonds are mostly stable and long lasting. Interations, on the other hand, can be strong or weak, with a gradation in strength depending on many factors. They can occur at greater distances compared to covalent bonds and could be stable or unstable. Van der Waal's forces, hydrophobic interactions, hydrogen bonds etc are all examples of weak interactions always occurring between molecules. When we talk about tRNA interacting with amino acid, we mean those weak linkages occurring at a distance. They're fleeting, can be easily broken apart and reconfigured. Now, all interactions may not be of equal strength. Enzymes like aaRS, for instance, interact much more strongly with their substrates. tRNA-amino acid interactions could be weaker than that, but nonetheless they still interact. You also have this stubborn idea in mind that aaRS, tRNA, amino acid all exist like solid blocks in one rigid, fixed shape. Not the case. Molecules are constantly changing shape as they interact with everything in their vicinity. They're flexible. Do you think DNA always exists in the classical double helix form inside the cell? If you think so, you're wrong. It's constantly changing shape. Like kids' bumper cars in an amusement park, ALL aaRSs will bump into ALL tRNAs as well as ALL amino acids . No physical barriers exist to prevent these molecules from bumping into one another. Everytime they bump into each other, there are interactions, which changes the shape, form and function of these molecules. In this sea of interactions, a particular set of aaRS, tRNA and amino acid associate in such a way that the resulting conformation (shape) of the complex favors covalent bonding of the amino acid with the tRNA in that complex. Now, this is what the paper is talking about. They don't say that tRNA selects amino acid all by itself or that aaRS selects tRNA all by itself. Interactions in the tripartite complex involving all 3 molecules determine the specificity of the reaction. The paper focuses on previously unexplained tRNA-amino acid associations in this complex. I hope now you can see where you're going wrong.Evolve
March 21, 2016
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///What are those man-made systems made of? Are they immaterial? If you push an A on your keyboard an A doesn’t appear on your screen? It does, but no molecules are involved?/// Not what I meant. Let's say you compare DNA to language - something routinely done by creationists. DNA is a chemical molecule, language has no chemistry whatsoever. DNA reacts, interacts & changes all on its own. Language does not unless humans intervene.Evolve
March 21, 2016
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Convention was established at our convenience. We could have established ANT to mean car with equal value. No constraints are present.Evolve
March 21, 2016
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Evolve: The word CAR does not relate to a car in any manner. Yes it does, and it's right there in your very next sentence. It just so happens that we humans decided to represent a car with that 3-letter word in English. IOW a convention was established. A code. Is it your position that this occurred supernaturally?Mung
March 21, 2016
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Evolve: I’m baffled to hear that you think this is symbolic! No, these are real physical interactions. The two are not mutually exclusive.Mung
March 21, 2016
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Evolve: You are fully aware of molecular interactions, you’re fully aware that biology is fueled by such interactions and it is totally unlike man-made systems where molecular interactions don’t apply. What are those man-made systems made of? Are they immaterial? If you push an A on your keyboard an A doesn't appear on your screen? It does, but no molecules are involved?Mung
March 21, 2016
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"There has to be something that establishes the relationship between the representation and that which is being represented. Without that you don’t have a semiotic system." Not necessarily. The word CAR does not relate to a car in any manner. It just so happens that we humans decided to represent a car with that 3-letter word in English.Evolve
March 21, 2016
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