RNA catalysts and the origin of life

:laughing:

Obam-na

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I did not know that! (But having thought about it, it’s not unlikely with mutations to tRNA)

Thank you.

Where did Dan suggest that you should “kneel to authority”? He was objecting to your characterization of everyone’s answers as “a lot of bluster” and included “insults” both of which were false. Feel free to disagree with the people here, but if you’re going to respond to them, don’t just claim baselessly that their answers are “bluster” and “insults.”

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As I said in my censured comment:

I’d be more impressed if any of them had acknowledged “yes” the set of sequences that encode aminoacyl-tRNA synthetases must be simultaneously coordinated with the products of those sequences in order for the system to function.

Here is the question: Does the set of sequences that encode aminoacyl-tRNA synthetases have to be coordinated with the products of those sequences in order for the system to function?

Perhaps you could have one of your experts step forward and explain how that statement is false.

First off, it isn’t a statement. As you say, it’s a question. Second, I don’t understand what the question means. I could try to puzzle it out, but it would be better if you would try harder to communicate.

Still, I can try to puzzle it out. Are you trying to present a paradox? aminoacyl tRNA synthetase mRNAs can only be translated with the assistance of aminoacyl tRNA synthetases, but aminoacyl tRNA synthetases can only be made by translating aminoacyl tRNA synthetase mRNAs. A chicken/egg dilemma! Was that it?

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The statement I was referring to was included in the original post, then repeated in my follow-up post, located immediately above the text you quoted.

In any case, the answer to your question is “no” it is not a paradox. It’s not a puzzle or a chicken and egg dilemma. It is the state of coordination required for the gene system to implement control over protein synthesis. This was characterized in physics as “rate-independent control of a rate-dependent process” about half a century ago.

You’ve said that you are unable to understand my statement well enough to say whether it is true or false. I will take you at your word.

You suggest that I should try harder to explain it, but already on this thread I’ve given specific examples of tRNA-synthetase genes and asked if the sequences contained within those genes have to be coordinated to the genetic code they establish. I don’t know how I could possibly ask the question any more clearly than that.

One of the other experts on this forum apparently understood my statement enough to provide an unambiguous answer — he said it was “Utterly objectively false”. For this expert, the genes that establish the genetic code need not be coordinated to the code they establish.

Of course, I’m just the pedestrian among experts. Even so, after 15 years of studying these specific issues, I can say that this conclusion will come as a striking revelation to many notable researchers around the globe — not to mention being as odds with the history of science, as it is clearly recorded in the literature.

Uh-huh. So you’ve now stated aminoacyl tRNA synthetase sequences are encoded in mRNA, and that to translate the mRNA you need tRNAs aminoacylated by aminoacyl tRNA synthetases. But you’ve not intended for this to be a chicken or egg dilemma(which came first? and how could they have emerged if both are required at the same time?).

Okay. But then why are you telling us about this “self-reference”? What is the overall purpose of pointing to this relationship you wish to make?

That’s a problem for you, since I have no idea what you meant by it. Does anyone else? What does “coordinated to the genetic code” mean? And “establish” seems like an odd word choice in context that also makes me unsure of its meaning.

Then you skills of communication seem wanting. First of all because you once again purport to ask a question but without finishing with a question mark.

Going over your “question” it’s obvious why we are left trying to guess what the heck you mean.

Taken at face value that statement means you have given us either the name of a gene encoding an aminoacyl-tRNA-synthetase, from a particular organism, or the DNA sequence of it (such as LARS2). That would be what a “specific example” of a tRNA synthetase gene is.

But it’s not at all clear whether you’ve done that. None of your posts contain a specific and unambigious example of a tRNA-synthetase gene. It is not clear that you’ve any gene or species name, nor referred to or linked or named a characterized genetic locus constituting a tRNA-synthetase gene of any known organism.

In a previous post you wrote:

If you are unaware that the sequence GARS or KARS or LARS have to be coordinated with the genetic code they establish, then I just don’t know what to tell you.

But you preface GARS, KARS, and LARS with the word “sequence”, not “sequences of” which implies you’re giving us literal amino acid sequences using Margeret Dayhoff’s single-letter amino acid alphabet, rather than the names of genes encoding aminoactyl-tRNA-synthetases.
So you would be specifying the sequences Glycine-Alanine-Arginine-Serine, Lysine-Alanine-Arginine-Serine, and Leucine-Alanine-Arginine-Serine, respectively.

So you must be unaware of what the words you use actually mean, leaving us having to guess what you could possibly mean instead. It is possible you have a coherent question in mind, but you haven’t actually asked one.

What genes, specifically? You haven’t given specific examples. And what do you mean by “within” those genes? As in an internal part of the DNA sequence that constitutes the gene? Like a particular exon? If you just meant the entirety of the gene, should you not have said “and asked if the sequences of those genes”?

Since you’ve not actually given any specific examples, you must be asking for just any arbitrarily picked tRNA-synthetase gene sequence, right? There is some general point you wish to make with tRNA synthetase gene sequences, without that point requiring you to give a specific example of such a gene. Right?

It gets worse.

You could also be confusing the amino acid sequence of the tRNA-synthetase enzyme with the DNA sequence of the gene that encodes that amino acid sequence. It’s not actually clear if you meant one or the other.

This one is almost completely incomprehensible and we’re left having to guess it’s meaning from the broader context of the discussion so far.

Taking a stab in the dark here I’ve tried to rephrase your not-even-a-question into something more coherent:

Is it possible to produce an aminoacyl-tRNA-synthetase enzyme without it being produced by translation of a messenger-RNA that encodes the amino acid sequence of that very same aaRS enzyme, using that enzyme to carry out it’s function as part of the translational process?

Is that the question you meant to ask?

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No, that was not the statement to which I responded. Did you forget?

The false statement you made was quite different:

Those are very different statements, and you’re still misusing the metaphorical “code.” And I offered the reason why it is false:

Are you pretending that you made a different claim because you did not understand what I wrote? What proportion of your functional proteins lack the methionine residue with which their synthesis began, falsifying your statement?

Really? Please list the 5 most recent papers you’ve read from the primary literature. If you don’t understand the meaning of “primary literature,” you should ask before listing papers that are not part of it.

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Did you come across “Upright Biped”, another autodidact on the chicken-and-egg issue of aminoacyl tRNA synthetases? He spent around 15 years on the recently defunct Uncommon Descent blog claiming this was an insurmountable barrier to the origin/early evolution of life.

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Possibly relevant to what he might be trying to talk about:

The structural basis of the genetic code: amino acid recognition by aminoacyl-tRNA synthetases | Scientific Reports.

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That’s a good read. The discussion emphasizes how the introduction of amino acids into the canonical code was not all at once

Step 1: Nonenzymatic preferential tRNA charging by inside/outside type
Step 2: Rodin-Ohno sense/antisense charging enzyme for inside/outside type
Step 3: Duplication and selection for specificity for subtypes until canonical set is produced

Hey look, a possible pathway…

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And there is of course the possibility that ribozymes initially carried out the key steps of amino acid activation and tRNA charging before the synthetases took over.

The smallest known ribozyme able to carry out tRNA aminoacylation is five nucleotides in length. Just five.

The ribozyme in blue with it’s substrates in red and green:
5nt ribozyme with substrates

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That’s amazing! It’s crazy how much we’ve learned about these things, and it saddens me that some people (probably a sizable chunk of the US population) want to stop this pursuit of knowledge due to their God-of-the-gaps views.

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Yes, I was about to cite those very papers (which you presented to me a while ago on The League of Reason forum)

It’s a tantalizing possibility, which would suggest that the ribosome used to be both the (primary) protein synthesizing catalyst and the (first?) genome.

I also recomend this talk by Eric Smith wherein he discusses this topic too:

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There’s so much knowledge about the evolutionary history of life (not just what kinds of biochemistry is possible), so many interesting details and clues that nobody who isn’t in these obscure fields of early evolution, the origin of life research, or molecular evolution and biochemistry knows about. Every day I feel like just telling someone about it. A few years ago I explained ancestral state reconstruction to my youngest brother and how scientists have been able to determine the functions of historical mutations that happened some times billions of years ago. He was mind blown and had the exact question I’ve had for a long time: Why don’t they tell us any of this on TV or anything?

People just have no idea what we’ve discovered. Even when they talk about evolution in some nature program on TV we’re typically just told about this giant shark that used to live 50 million years ago or whatever, or a sabertooth cat or whatever other dramatic predator. Big scary beast with teeth, fossil millions of years. That’s about what the general public knows about evolution and research in it. Some times microbes evolve resistance to antibiotics, but otherwise the study of evolution is finding fossils of dinosaurs or ancient giant sharks to put in a museum. That’s about it. There is SO MUCH more.

I am amazed of what I have learned over the last 16 or so years.

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