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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
"Only someone completely ignorant of ID, or someone intent on willfully misrepresenting ID, would say that ID holds to the position that molecules do not interact." 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. But you never acknowledge these facts wholeheartedly, because if you do the whole ID premise will collapse. ID hangs on through bad analogies between biology and man-made stuff.Evolve
March 21, 2016
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"Withouth the aaRS?" What? Without the aaRS you won't see much because it is the tripartite complex involving all 3 molecules - tRNA, amino acid and aaRS that produces the right conformation to carry out the reaction.Evolve
March 21, 2016
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Evolve: That’s how semiotic systems work. No, it isn't. 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.Mung
March 21, 2016
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Only someone completely ignorant of ID, or someone intent on willfully misrepresenting ID, would say that ID holds to the position that molecules do not interact. Sheesh.Mung
March 21, 2016
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Evolve: "If you test this in the lab, you’ll see what you’ve always seen – one tRNA gets charged with one amino acid." Withouth the aaRS? OK, I don't want to waste any more of my time with you. You are really a fool.gpuccio
March 21, 2016
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“Let’s be clear: if you want to affirm “the intrinsic ability of tRNAs to discriminate amino acids”, you must show in the lab that tRNAs discriminate aminoacids by biochemical interaction. Where is that evidence?” tRNAs discriminate amino acids by physical interaction, not biochemical. If you test this in the lab, you’ll see what you’ve always seen - one tRNA gets charged with one amino acid. The paper here provides an explanation for why that’s the case through regression analysis. “If you just build a regression between sequences and the aminoacid which is bound by an enzyme, what you are analyzing are codes. Indeed, the authors know that very well, and that’s why they always use the word “coding” which you seem not to like at all.” Codes or not, these associations are the result of molecular interactions which the authors make abundantly clear in the paper (e.g Fig 4) and in the review that followed. It is unbelievably stupid on your part to deny that fact. “Again, you are not able to distinguish between facts and mere speculations, or abstract models unsupported by observations.” Lol!Evolve
March 21, 2016
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Evolve: Just for further clarification here is a quote from the PDB page for aminoacyl tRNA synthetases:
Finding the Proper Mate As you might expect, many of these enzymes recognize their tRNA molecules using the anticodon. But this may not be possible in some cases. Take serine, for instance. Six different codons specify serine, so seryl-tRNA synthetase must recognize six tRNA molecules with six different anticodons, including AGA and GCU, which are entirely different from one another. So, tRNA molecules are also recognized using segments on the acceptor end and bases elsewhere in the molecule. One base in particular, number 73 in the sequence, seems to play a pivotal role in many cases, and has been termed the discriminator base. In other cases, however, it is completely ignored. Note also that each enzyme must recognize its own tRNA molecules, but at the same time, it must not bind to any of the other ones. So, each tRNA has a set of positive interactions that match up the proper tRNA with the proper enzyme, and a set of negative interactions that block binding of improper pairs. For instance, the aspartyl-tRNA synthetase shown here (entry 1asz ) recognizes the discriminator base and 4 bases around the anticodon. But, one other base, guanine 37, is not used in binding, but must be methylated to ensure that the tRNA does not bind improperly to the arginyl-tRNA synthetase.
As you can certainly see, the problem is in the coupling of the aaRS to the correct tRNA. The aminoacid has no role, it is simply recognized by the aaRS. Which is not a simple task. Again. from the PDB page:
Aminoacyl-tRNA synthetases must perform their tasks with high accuracy. Every mistake they make will result in a misplaced amino acid when new proteins are constructed. These enzymes make about one mistake in 10,000. For most amino acids, this level of accuracy is not too difficult to achieve. Most of the amino acids are quite different from one another, and, as mentioned before, many parts of the different tRNA are used for accurate recognition. But in a few cases, it is difficult to choose just the right amino acids and these enzymes must resort to special techniques. Isoleucine is a particularly difficult example. It is recognized by an isoleucine-shaped hole in the enzyme, which is too small to fit larger amino acids like methionine and phenylalanine, and too hydrophobic to bind anything with polar sidechains. But, the slightly smaller amino acid valine, different by only a single methyl group, also fits nicely into this pocket, binding instead of isoleucine in about 1 in 150 times. This is far too many errors, so corrective steps must be taken. Isoleucyl-tRNA synthetase (PDB entry 1ffy ) solves this problem with a second active site, which performs an editing reaction. Isoleucine does not fit into this site, but errant valine does. The mistake is then cleaved away, leaving the tRNA ready for a properly-placed leucine amino acid. This proofreading step improves the overall error rate to about 1 in 3,000.
These are facts. These are biological interactions.gpuccio
March 21, 2016
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Evolve: I think there is no hope with you. An association between the kind of nucleotide sequences which are recognized by the aaRS in the acceptor stem and the aminoacid that the aaRS binds to that tRNA ia a code, not an interaction. The interaction would be if the tRNA were able to select the aminoacid by itself, and not because its sequences are recognized by the aaRS. The paper, which you obstinately misunderstand, is all about codes: it just suggests that one part of the code could be older, in particular the acceptor stem code, because the urzymes modeled by the authors can recognize that code, but not the anticodon code. Maybe, or maybe not. Anyway, the simple fact is that there are two levels of code, one in the sequence of the nucleotides in the acceptor stem, and the other in the sequence of nucleotides in the anticodon part. Both are symbolic coding sequences, and together they allow the aaRS to recognize the correct tRNA and charge it with the correct AA. Let's say it this way. The aaRS must recognize the correct tRNA to couple it with the correct aminoacid for which that aaRS is specific (remember, there are 20 of them, one for each aminoacid). Now, the essence of the paper is that the aaRS recognizes the tRNA by two different messages: one is in the acceptore stem, and it informs the aaRS about the size of the aminoacid which has to be charged. So, the aaRS can recognize tRNAs which are coding for the correct size. At the same time, the anticodon part bears a signal which points to the polarity. The sum of size and polarity, as coded in the two different parts of the tRNA, allows the aaRS to recognize the correct, specific tRNAs, and charge them with the correct aminoacid. This system, although complex, allows for precision, because it guarantees that the aminoacid in the end will be exactly the one coded for by the original codon in the DNA gene, minimizing the possibility of errors. In no moment of this procedure does the tRNA "select" the aminoacid. The tRNA cannot select any aminoacid by itself. It can only do it by interacting with the aaRS, and exhibiting its two signals to the enzyme. The key to the decoding is in the aaRS, as we have always known. These are the facts. All the rest are speculations on how and why such a system could have originated, according to the current dogma of neo darwinism. You must make up your mind: do you still affirm that the paper demonstrates the "intrinsic ability of tRNAs to discriminate amino acids"? Because, you know, when you just state: "The genetic code is of course there, but increasing evidence suggests that it didn’t exist in the present form right from the beginning. That’s what I discussed above. Ancestral aaRSs, ancestral tRNAs and ancestral ribosomes were all different from modern-day versions. Therefore, alternative modes of rudimentary protein synthesis and RNA replication are likely to have preceded the current mechanisms." you are simply considering and sponsoring the speculations in the paper, and you are free to do that, as much as I am free not to believe them at all. But if you say that the paper demonstrates the "intrinsic ability of tRNAs to discriminate amino acids", then you are just a fool.gpuccio
March 21, 2016
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“Interesting speculations, all centered however on the role of aaRSs. Nothing more.” These are informed speculations, not wild speculations. They’re based on available data. “While darwinists fight about RNA worlds or peptide/RNA worlds of which we have absolutely no evidence, the genetic code is there, symbolic as ever, and the recognition of tRNA and AA by aaRSs is there, symbolic as ever.” And creationists do nothing more than misrepresent all the hard work of biologists while doing hardly any experiments of their own or to try and falsify their fanciful ideas. Meanwhile, it’s too ignorant of you to claim that there’s no evidence for the RNA world or RNA/peptide world. There is substantial evidence but not conclusive enough to formulate a theory. The genetic code is of course there, but increasing evidence suggests that it didn't exist in the present form right from the beginning. That's what I discussed above. Ancestral aaRSs, ancestral tRNAs and ancestral ribosomes were all different from modern-day versions. Therefore, alternative modes of rudimentary protein synthesis and RNA replication are likely to have preceded the current mechanisms.Evolve
March 21, 2016
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"It is a regression study showing association between the two things. It is not a biochemical study showing any kind of biochemical interaction between tRNA and AA. Is that clear?" But you're totally missing the fact that association cannot happen without interaction, which Carter elaborates in his review. I find that baffling. How else can tRNA distinguish between amino acids based on their size or polarity if there's absolutely no interaction? What rubbish is that? I think you're confusing interaction to be some kind of biochemical reaction producing a product. No, interactions here mean things like Van der Waal's forces and hydrogen bonds between the nucleotides in the tRNA and residues in the amino acid or peptide.Evolve
March 21, 2016
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Evolve: Your quote from the paper. “We suggest that genetic coding evolved in distinct stages. Initial discrimination on the basis of size may have allowed coding by tRNA acceptor stems to ensure that the earliest peptides were ?-structures with alternating large and small side-chains, to interact with RNA, and only later encoded globular conformations with greater catalytic activity. The earliest peptides may have included the unstructured peptide tails that stabilize ribosomal RNAs.” These are not facts, but mere speculations. The facts are the statistical association between certain sequences of nucleotides in the accepètor stem (a code, by admission of the authors themselves) and the kind of aminoacid which is bound to tRNA by the aaRS. Let's be clear: if you want to affirm "the intrinsic ability of tRNAs to discriminate amino acids", you must show in the lab that tRNAs discriminate aminoacids by biochemical interaction. Where is that evidence? If you just build a regression between sequences and the aminoacid which is bound by an enzyme, what you are analyzing are codes. Indeed, the authors know that very well, and that's why they always use the word "coding" which you seem not to like at all. Again, you are not able to distinguish between facts and mere speculations, or abstract models unsupported by observations.gpuccio
March 21, 2016
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Evolve: "The paper is about the intrinsic ability of tRNAs to discriminate amino acids," Nonsense. Can you please show where tRNAs are shown to discriminate between aminoacids? Did they do it in tyhe lab? Do you understand what you are reading?gpuccio
March 21, 2016
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Evolve: Apparently, you cannot distinguish facts from mere speculations. In the Carter Wolfenden paper of 2015 there is absolutely no fact about direct interactions between the tRNA and the aminoacid. They are not using the word "code" as a game. They are using it because that's what they are analyzing: a symbolic code where there is correspondence between the sequence of nucleotides in the acceptor stem and the anticodon region, which are both recognized by the aaRS, and the properties (size and polarity) of the specific AA which will be bound to the tRNA by the aaRS. It is a regression study showing association between the two things. It is not a biochemical study showing any kind of biochemical interaction between tRNA and AA. Is that clear? Those are the facts. Symbol + symbol equates final symbology (the classic genetic code). The rest are the usual speculations, absolutely unsupported by facts. For example, these are the conclusions from the Carter review:
4. Conclusions The structural biology of aminoacyl-tRNA synthetases (aaRS) furnishes a platform from which to examine experimentally the steps by which pre-biological chemistry gave rise to the universal genetic code, thereby creating genetics. A key stage in the process was likely driven by “Urzymes,” which are models we developed to represent the core catalysts embedded within two distinct, contemporary aaRS superfamilies. aaRS Urzymes contain only ~15% of the total mass of the largest synthetases. They retain ~60% of their catalytic proficiency [13], but less than 20% of their specificity [20]. These properties match those necessary to produce statistical ensembles of functional peptides, as proposed by Woese. The two distinct classes of aaRS that translate the code today were formerly considered to have arisen independently. We used Urzymes to show that, rather than arising independently, the two classes probably descended from opposite strands of the same ancestral gene [17], as proposed by Rodin and Ohno [8]. Our group has ventured both backward in time [12,20], investigating likely precursors of Urzymes, and forward in time, investigating how Urzymes subsequently developed epistatic mechanisms [25,26] that increased specificity, enabling the evolution of the universal genetic code. As Urzymes cannot recognize the anticodon stem-loop, it is likely that the acceptor stem code preceded the canonical genetic code. The acceptor stem code favors the capacity of polypeptide sequences to interact with double-stranded RNA. We link these numerous biochemical, phylogenetic, and structural observations to the Carter & Kraut structural model to form a credible, testable alternative to the RNA World Hypothesis for the origin of translation and the genetic code. This work does not presuppose an “RNA world,” which we feel is based on the wrong assumptions. Rather, comparison of predictions based on the two hypotheses indicate that a peptide/RNA world is substantially more predictive, and hence a more credible and probable alternative to the prevailing idea that life originated from a single polymer with both catalytic and informational functions.
Interesting speculations, all centered however on the role of aaRSs. Nothing more. While darwinists fight about RNA worlds or peptide/RNA worlds of which we have absolutely no evidence, the genetic code is there, symbolic as ever, and the recognition of tRNA and AA by aaRSs is there, symbolic as ever. If you really believe that tRNAs recognize their aminoacid according to biochemical laws, and self-charge themselves with it, please show me the experiments where those facts are observed. The only fact is that aaRSs recognize their tRNA symbolically, and charge it with the appropriate AA because their complex structure is organized to do so. This is the simple truth. Facts please, if you have them.gpuccio
March 21, 2016
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The paper states that two levels of coding are present when the aaRS interacts with the tRNA: both are symbolic, and together they determine the correct association between the tRNA and the corresponding aminoacid according to the genetic code we all know.
Wrong. it’s not just the aaRS that interacts with the tRNA, but also the amino acid. The tRNA is anything but a passive vehicle, it actively sorts amino acids based on their properties. Figure 4 of the paper shows how stereochemical specification might have worked: “Acceptor stem coding may have conferred a selective advantage by distinguishing smaller from larger amino acids and identifying ?-branched, aliphatic, and carboxylate side-chains. Fig. 4 shows how only small side-chains fit between peptide and RNA bases, whereas side-chains pointing away from the RNA are not so constrained. Coding of amino acid size could thus have helped preserve these patterns in transitions from a proposed direct, stereochemical specification (49, 50) to triplet coding. The conformational propensity of ?-branched side-chains could similarly have favored ?-secondary structures”
The paper is about how the genetic code is implemented by the interaction between the aaRS and the two sequences of nucleotides in the anticodon part and the acceptor part of the tRNA.
Nope. The paper is about the intrinsic ability of tRNAs to discriminate amino acids, which in turn provides clues to ancestral translation in the absence of codon-anticodon pairing. Initial acceptor stem-based coding may not have allowed production of fully folded globular proteins like today because discrimination on the basis of hydrophobicity was absent: “We suggest that genetic coding evolved in distinct stages. Initial discrimination on the basis of size may have allowed coding by tRNA acceptor stems to ensure that the earliest peptides were ?-structures with alternating large and small side-chains, to interact with RNA, and only later encoded globular conformations with greater catalytic activity. The earliest peptides may have included the unstructured peptide tails that stabilize ribosomal RNAs.”Evolve
March 21, 2016
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"By the way, you could also try to explain how the aaRS, even in their urzyme form, came into existence," See my first post, #93Evolve
March 21, 2016
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I’m baffled to hear that you think this is symbolic! No, these are real physical interactions. How else do you think specific parts of the tRNA molecule can select for amino acids? Carter discusses this paper in his review, which I’ve already mentioned more than once. I’m quoting from the review where he mentions acceptor stem coding: http://www.mdpi.com/2075-1729/5/1/294/htm "Figure 9 illustrates aspects of the Carter and Kraut model consistent with acceptor stem base coding. Large amino acid side chains at inward-facing positions would seriously disrupt peptide–RNA interactions in three ways. Displacing the antiparallel ?-structure to higher radii would (i) eliminate the synchronous periodicity of dipeptides and bases; (ii) break the peptide-sugar phosphate hydrogen bonds; and (iii) break Van der Waals interactions between other inward-pointing side chains and the RNA bases. Accepter stem coding on the basis of amino acid size therefore appears central to preserving such interactions. ?-branched side chains are preferentially observed in extended ?-structure in contemporary proteins [57]. Selectively identifying such side chains would have the advantage of enforcing extended secondary structures, also preserving peptide–RNA interactions by a complementary constraint." Such molecular associations between RNA and peptides were modelled by Carter back in 1974: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC387987/ You seem to be missing all this.Evolve
March 21, 2016
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Evolve: This is the level of highest fact independent speculation that you can find at the end of the paper: "Although we are not in a position to address the question of how aminoacylated tRNA acceptor stems might have been aligned in accordance with a primordial mRNA without anticodons, Rodin and Ohno suggested that reconstructed tRNA acceptor stems display evidence of complementary sequences (59). Our results revive the possibility that such complementarity and/or lateral-loop-loop base-pairing (60) might have aligned acylated acceptor stems, anticipating the assembly of peptides according to a message." IOWs, the data in the paper are merely about the coding power of the acceptor stem and the anticodon, mediated by the recognition by the aaRS. The paper states that two levels of coding are present when the aaRS interacts with the tRNA: both are symbolic, and together they determine the correct association between the tRNA and the corresponding aminoacid according to the genetic code we all know. The paper is about how the genetic code is implemented by the interaction between the aaRS and the two sequences of nucleotides in the anticodon part and the acceptor part of the tRNA. tRNA is a passive vehicle of information in all this process: it's the aaRS which recognizes the information, and binds the correct AA. From the paper: "Dual coding for amino acids by tRNA acceptor stem and anticodon bases correlates strongly with experimental values for two linearly independent branches of the thermodynamic cycle of vapor to solvent transfers, Kv>c and Kv>w (SI Appendix, Fig. S1). That cycle (19, 28) affords a comprehensive experimental description of how the 20 amino acids direct folding (Fig. 1 C–E), supporting the view that acceptor stem and anticodon bases compose full, complementary, and independent, specifications for the 20 canonical amino acids by coding, respectively, for size and polarity."gpuccio
March 21, 2016
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Evolve: By the way, you could also try to explain how the aaRS, even in their urzyme form, came into existence, and how the code worked in their absence? Or are you suggesting that such complex enzymes were there even while molecular information was not yet transmitted by a genetic code? Just to understand what you think.gpuccio
March 21, 2016
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Evolve: It's you who are missing the point. If you’re confused by the non-technical press release, then look at the technical paper. Believe me, it's better! It's always the aaRS which recognizes both the anticodon region and the acceptor region of tRNA. The paper only analyzes interesting details about how the genetic code is implemented, at two different levels, in the interaction between the aaRS and the two different regions of tRNA. That is done by a regression method which relates the type of AA coded with the nucleotide sequence (code), and there is no evidence of biochemical interactions between the tRNA and the AA. So, the interaction is always symbolic, because it depends on the structure and specific configuration of the repository of the code (the aaRS). There is absolutely no evidence in the paper of a direct interaction of the tRNA with the aminoacid, as you seem to believe. So, if you are still convinced that such a direct interaction is the basis for the code, could you please point to the facts in the paper which support that belief? Otherwise, your discourse is senseless.gpuccio
March 21, 2016
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gpuccio, You’re missing the points altogether while making a big deal of the word ‘code’. By ‘code’ they simply mean specific parts of the tRNA molecule select for specific properties of amino acids. This selection happens through structure, conformations and interactions of the molecules involved. If you’re confused by the technical paper, then look at the non-technical press release again: “That link suggests to us that there was a second, earlier code that made possible the peptide-RNA interactions necessary to launch a selection process that we can envision creating the first life on Earth.” “Thus, Carter said, RNA did not have to invent itself from the primordial soup. Instead, even before there were cells, it seems more likely that there were interactions between amino acids and nucleotides that led to the co-creation of proteins and RNA.” http://news.unchealthcare.org/news/2015/june/new-evidence-emerges-on-the-origins-of-life-the-genetic-code-developed-in-two-distinct-stages The fact that molecular interactions are involved differentiates biology from man-made semiotic systems. This is the key point. For example, in language, the shape ‘A’ can potentially represent any sound. It can represent B,C,D,E etc. It is we humans who randomly assigned the sound A to the shape ‘A’. That’s how semiotic systems work. But in biology, a codon does not have the potential to randomly represent any amino acid. It is constrained to code for a particular amino acid that interacts in the right manner with the codon’s corresponding tRNA and associated aaRS. It’s the physicochemical interaction among the tRNA, amino acid and aaRS molecules that determines which amino acid is selected. There’s no freedom of choice here, it boils down to chemistry. The implications of this is even more far-reaching especially in light of related previous work, which I discussed above. See the review by Crater, especially. Collectively they point to ancestral tRNAs lacking anticodons, ancestral aaRSs that only bind the tRNA acceptor arm and ancestral ribosomes with only the peptide-bond forming rRNA ribozyme. Such a primitive system can join amino acids to produce peptides (short proteins) in the absence of mRNA codons or codon-anticodon pairing. This negates the need for there being mRNA-based code right from the start. That may have evolved later.Evolve
March 21, 2016
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Mung: I am still waiting for someone to give a credible definition of "natural". Never a word so ambiguous was so universally, and sadly, used (except, maybe, "love" :) ).gpuccio
March 20, 2016
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Well said in #96, Mung. Even the joins, the seams, between our integrated and coordinated, personal worlds are established by QM.Axel
March 20, 2016
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Evolve: Thank you for providing a link to a very interesting paper. But... I suspect that you really don't understand what the paper is about. You say: "However, a paper from last year by Carter & Wolfenden shows that tRNA can discriminate between amino acids based upon its nucleotide sequence. The sequence at the acceptor stem of tRNA sorts amino acids by size, while the sequence at the anticodon end sorts amino acids by polarity." Where did you get that strange idea? The paper is about the properties of the code, not about physical interactions between tRNAs and the aminoacids, as you seem to believe. I will quote from the paper:
Here, we show that acceptor stems and anticodons, which are at opposite ends of the tRNA molecule, code, respectively, for size and polarity.
From the "significance" box. Emphasis added. IOWs. the point of the paper is that the recognition between aaRS and tRNA is symbolic, as we all know, but that the symbolic recognition is achieved at two separate levels: the aaRS recognizes separately two different regions of the specific tRNA, the acceptor stem and the antocodon. Each of those two regions implements a code, and each of the two codes is related to two complementing levels of abstraction about the biochemical properties of the aminoacid: size and polarity. IOWs, the code is more complex than we thought, but it is a code just the same, at all its levels. Here is the abstract of the paper:
Aminoacyl-tRNA synthetases recognize tRNA anticodon and 3? acceptor stem bases. Synthetase Urzymes acylate cognate tRNAs even without anticodon-binding domains, in keeping with the possibility that acceptor stem recognition preceded anticodon recognition. Representing tRNA identity elements with two bits per base, we show that the anticodon encodes the hydrophobicity of each amino acid side-chain as represented by its water-to-cyclohexane distribution coefficient, and this relationship holds true over the entire temperature range of liquid water. The acceptor stem codes preferentially for the surface area or size of each side-chain, as represented by its vapor-to-cyclohexane distribution coefficient. These orthogonal experimental properties are both necessary to account satisfactorily for the exposed surface area of amino acids in folded proteins. Moreover, the acceptor stem codes correctly for ?-branched and carboxylic acid side-chains, whereas the anticodon codes for a wider range of such properties, but not for size or ?-branching. These and other results suggest that genetic coding of 3D protein structures evolved in distinct stages, based initially on the size of the amino acid and later on its compatibility with globular folding in water.
Emphasis mine. So, I really can't understand why you say that: "This means that a codon is forced to code for a particular amino acid because its cognate tRNA is limited or constrained by physical interactions with that particular amino acid. This is unlike Morse code or language, where symbols merely stand for something." Emphasis mine. I am afraid you did not understand what the paper is discussing. I suggest that you correct your position, before any further discussion can be done on any other aspect you mention.gpuccio
March 20, 2016
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The problem is science has never ever confirmed supernaturalistic explanations for anything in its entire history. Everything about science and nature is supernatural. The desire to call it natural is metaphysical, not scientific.Mung
March 20, 2016
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UB and all others supporting him are wrong. I wouldn't have it any other way.Mung
March 20, 2016
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UB @ 39 disses the naturalistic route taken by science: "Yes, in his writing Barbieri has made it abundantly clear that he follows a fully naturalistic metaphysics. That is fine by me — I only have a problem with it when he (or anyone else) wants to force that view on the practice of science. For instance, in his “Brief History of Biosemiosis” (I believe was the title) his attempt at putting a natural-only guise on semiosis stuck out like a sore thumb." The problem is science has never ever confirmed supernaturalistic explanations for anything in its entire history. There has been no evidence for it. In contrast, natural explanations have aptly and satisfactorily solved many scientific questions. In fact science has shown, in several instances, that supernatural hypotheses are wrong and natural explanations can better account for the data. Therefore, the confidence in such explanations is pretty much nonexistent from science's perspective. That’s the reason why science still proposes naturalistic hypotheses for outstanding questions.Evolve
March 20, 2016
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UB and all others supporting him are wrong. I have told this here before, but UB continues to tout this as the killer argument for ID. It isn't. Now, new studies are helping to further show why. UB’s model is problematic on two counts: 1) He says that the codon does not determine the amino acid, it merely represents it. By this he implies that a codon could potentially represent any amino acid, but it was assigned to represent a particular one by, er, the intelligent designer. However, a paper from last year by Carter & Wolfenden shows that tRNA can discriminate between amino acids based upon its nucleotide sequence. The sequence at the acceptor stem of tRNA sorts amino acids by size, while the sequence at the anticodon end sorts amino acids by polarity. See: http://www.pnas.org/content/112/24/7489.long Non-technical press release: http://news.unchealthcare.org/news/2015/june/new-evidence-emerges-on-the-origins-of-life-the-genetic-code-developed-in-two-distinct-stages This means that a codon is forced to code for a particular amino acid because its cognate tRNA is limited or constrained by physical interactions with that particular amino acid. This is unlike Morse code or language, where symbols merely stand for something. UB fatally ignores the role of chemistry in biology, which is lacking in man-made semiotic systems. He thinks that chemical interactions are only occurring at the codon-anticodon interface. Nope. 2) UB assumes that the present-day translation system (DNA-RNA-Protein) held true right from the beginning. Therefore, someone (i.e. the intelligent designer) had to create the genetic code in the first place, then create tRNAs, aaRSs, ribosomes etc to set translation of that genetic code in motion. However, new studies suggest that the primordial translation system could have been different. For instance, in 2013 Carter reconstructed ancestral versions of the two superfamilies of aaRS enzymes, called Urzymes. They retain 60% of the catalytic activity of present-day aaRSs: http://www.jbc.org/content/288/37/26856.abstract These Urzymes only recognise the tRNA acceptor arm, but not the tRNA anticodon part. Yet they can carry out aminoacylation of the tRNA. This suggests that initial tRNA precursors lacked the anticodon end altogether. A 'stereochemical code' based on size may have risen first and codon-anticodon based translation may have risen only later. Now, one can still ask how did Urzymes or proteins, in general, arise in the first place. In the following review, Carter argues for a model he proposed along with Kraut back in 1974: http://www.mdpi.com/2075-1729/5/1/294/htm (see Figs: 1, 2 and also 10) In this model, physicochemical interactions between RNA and peptides promote reciprocal autocatalysis, i.e, RNA can be polymerised by peptides and peptides can be polymerised by RNA. This is possible if early tRNA precursors bound amino acids based on their size and branching. Alternatively, it has been suggested that lateral association of tRNA molecules can bring their attached amino acids close enough for peptide bond formation on an ancestral ribosome (which is essentially a ribozyme), without the need for an mRNA. See: http://www.ncbi.nlm.nih.gov/pubmed/9222500?dopt=Abstract Of course, many of these models and suggestions await experimental verification and refinements. More studies are definitely needed. But the take home message is that we have not exhausted all possible physicochemical explanations for the origin of the genetic translation system as we know it. Far from it. UB ignores or misses many papers in the literature to reach his ill-defined conclusion.Evolve
March 20, 2016
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REW, You suggested that I (and others) are biased because there are properties of the code that we “appreciate in the abstract”, and as such, it is clouding our judgement -- that more or less, we are seeing things that are not there. I was hoping you might return and clarify what property or properties are these that are not actual working properties of the code system?Upright BiPed
March 18, 2016
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Heavens to Betsy !!! First, PLOS allows someone to utter foul language in the scientific literature, now KLI and MIT Press have gone off the rails as well. Michael Behe himself is cited without reference to his blasphemy towards Chuck. Off with their heads. :)Upright BiPed
March 18, 2016
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Mike Behe makes The Vienna Series in Theoretical Biology:
For example, systems of many complex interdependent parts can appear unevolvable - especially when any small change in the system causes the system to cease functioning (Behe 1996).
Mung
March 18, 2016
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