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The RNA world has problems

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  • The RNA world has problems

    Critical problems:

    Source: Evolution News

    Experiments invariably require highly orchestrated physical and chemical conditions to produce the desired results. They also consistently start with ribozymes from cells and carefully modify them to perform such targeted actions as combining RNA fragments or replicating an RNA template. And, they regularly use concentrations of ribozymes and templates that correspond to at least trillions of RNAs in 1 ml of solution. The replication rates would drop below the degradation rates if concentrations dropped below a million RNAs per ml. Replication would then continuously decrease until it ceased.

    Even with all of this assistance, the error rate for polymerases is typically 3-10 percent per nucleotide. The Attwater et al. 2018 study reported the lowest error rate at 2.6 percent per nucleotide. Yet, this claim must be greatly qualified. The experiment did not use individual nucleotides as the building blocks for new RNA. It instead used nucleotide triplets (three joined nucleotides) at concentrations corresponding to quadrillions of triplets per ml. In addition, the investigators had to manually link 25 percent of the triplets together, so they could bind to a template as a larger chain. In other words, the polymerase failed to replicate a template without the researchers linking sets of nucleotides together beforehand.

    Of key importance, the high error rates in all experiments guarantee that the information in any sequence longer than 30 nucleotides would be completely lost after several rounds of replication. Polymerases have sequence lengths that are typically close to 200 nucleotides, so replicated copies — assuming that polymerases could copy themselves — would become entirely nonfunctional after only a few generations.

    Source

    © Copyright Original Source



    They continue:

    Source: Evolution News

    Even more problematic, no polymerase has ever been constructed, or likely will be constructed, that could replicate more than a small fraction of itself. The challenge is that polymerases cannot efficiently replicate long RNAs with the complex folded structures that are essential for ribozyme functions. Attwater et al. clearly describe the problem:

    "However, even the most highly-evolved RPRs [RNA polymerase ribozymes] are substantially impeded by template secondary structures. Such structures are ubiquitous in larger, functional RNAs (including the RPRs themselves) and generally indispensable for function. The strong inhibitory role of this central feature of RNA leads to an antagonism between the degree to which an RNA sequence is able to fold into a defined three-dimensional structure to encode function (such as catalysis) and the ease with which it can be replicated."

    © Copyright Original Source




    So the RNA world appears to have roadblocks, even an essential roadblock as in the folding problem outlined above.

    Blessings,
    Lee
    Last edited by lee_merrill; 04-25-2021, 12:09 PM.
    "What I pray of you is, to keep your eye upon Him, for that is everything. Do you say, 'How am I to keep my eye on Him?' I reply, keep your eye off everything else, and you will soon see Him. All depends on the eye of faith being kept on Him. How simple it is!" (J.B. Stoney)

  • #2
    Same old same old.

    Lee pontificating on topics that he has a proven track record of not understanding (and showing no interest in learning about it), and uncritically cites a source that has a proven track record for either not having a clue about what they are discussing or quite deliberately misrepresenting and outright lying.

    I'm always still in trouble again

    "You're by far the worst poster on TWeb" and "TWeb's biggest liar" --starlight (the guy who says Stalin was a right-winger)
    "Of course, human life begins at fertilization that’s not the argument." --Tassman

    Comment


    • #3
      Originally posted by rogue06 View Post
      Same old same old.

      Lee pontificating on topics that he has a proven track record of not understanding (and showing no interest in learning about it), and uncritically cites a source that has a proven track record for either not having a clue about what they are discussing or quite deliberately misrepresenting and outright lying.
      To validate your evaluation of his sources:

      A ribozyme that can replicate large, complex RNA molecules:
      https://www.pnas.org/content/117/6/2906

      A ribozyme with high fidelity replication:
      https://pubmed.ncbi.nlm.nih.gov/12873135/

      A fully processive ribozyme (meaning it makes a full copy of what it starts on):
      https://science.sciencemag.org/content/371/6535/1225

      All of which mean that this:
      "Even more problematic, no polymerase has ever been constructed, or likely will be constructed, that could replicate more than a small fraction of itself."
      Was a lie when it was written.

      2 of those papers have come out in the past year. But sure Lee, it's stuck at a roadblock.


      "Any sufficiently advanced stupidity is indistinguishable from trolling."

      Comment


      • #4
        Originally posted by lee_merrill View Post
        Critical problems:

        Source: Evolution News

        Experiments invariably require highly orchestrated physical and chemical conditions to produce the desired results. They also consistently start with ribozymes from cells and carefully modify them to perform such targeted actions as combining RNA fragments or replicating an RNA template. And, they regularly use concentrations of ribozymes and templates that correspond to at least trillions of RNAs in 1 ml of solution. The replication rates would drop below the degradation rates if concentrations dropped below a million RNAs per ml. Replication would then continuously decrease until it ceased.

        Even with all of this assistance, the error rate for polymerases is typically 3-10 percent per nucleotide. The Attwater et al. 2018 study reported the lowest error rate at 2.6 percent per nucleotide. Yet, this claim must be greatly qualified. The experiment did not use individual nucleotides as the building blocks for new RNA. It instead used nucleotide triplets (three joined nucleotides) at concentrations corresponding to quadrillions of triplets per ml. In addition, the investigators had to manually link 25 percent of the triplets together, so they could bind to a template as a larger chain. In other words, the polymerase failed to replicate a template without the researchers linking sets of nucleotides together beforehand.

        Of key importance, the high error rates in all experiments guarantee that the information in any sequence longer than 30 nucleotides would be completely lost after several rounds of replication. Polymerases have sequence lengths that are typically close to 200 nucleotides, so replicated copies — assuming that polymerases could copy themselves — would become entirely nonfunctional after only a few generations.

        Source

        © Copyright Original Source



        They continue:

        Source: Evolution News

        Even more problematic, no polymerase has ever been constructed, or likely will be constructed, that could replicate more than a small fraction of itself. The challenge is that polymerases cannot efficiently replicate long RNAs with the complex folded structures that are essential for ribozyme functions. Attwater et al. clearly describe the problem:

        "However, even the most highly-evolved RPRs [RNA polymerase ribozymes] are substantially impeded by template secondary structures. Such structures are ubiquitous in larger, functional RNAs (including the RPRs themselves) and generally indispensable for function. The strong inhibitory role of this central feature of RNA leads to an antagonism between the degree to which an RNA sequence is able to fold into a defined three-dimensional structure to encode function (such as catalysis) and the ease with which it can be replicated."

        © Copyright Original Source




        So the RNA world appears to have roadblocks, even an essential roadblock as in the folding problem outlined above.

        Blessings,
        Lee
        Don't you get tired of repeating yourself with non-science sources that have been repeatedly refuted.
        Glendower: I can call spirits from the vasty deep.
        Hotspur: Why, so can I, or so can any man;
        But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

        go with the flow the river knows . . .

        Frank

        I do not know, therefore everything is in pencil.

        Comment


        • #5
          Originally posted by TheLurch View Post
          To validate your evaluation of his sources...
          The first two references are behind a paywall, so I can't read the full papers.

          A ribozyme that can replicate large, complex RNA molecules:
          https://www.pnas.org/content/117/6/2906
          Source: PNAS

          Moreover, the clamp-like mechanism of this polymerase could eventually enable strand invasion, a critical requirement for replication in the early evolution of life.

          © Copyright Original Source


          Sounds like a critical requirement for replication is missing.

          A ribozyme with high fidelity replication:
          https://pubmed.ncbi.nlm.nih.gov/12873135/
          Source: PubMed

          This method allowed us to demonstrate that the polymerase ribozyme, despite its inefficiency, is partially processive.

          Source

          © Copyright Original Source


          So it's partial, and slow.

          A fully processive ribozyme (meaning it makes a full copy of what it starts on):
          https://science.sciencemag.org/content/371/6535/1225
          Source: PNAS

          This result represents the most complex functional RNA that has been synthesized by a ribozyme from mononucleotide substrates, and it suggests that a similar in vitro evolution strategy could lead to further improvements that enable the polymerase to synthesize itself. However, the fidelity of RNA synthesis is modest, especially on the most challenging templates. Thus, only a very small fraction of the assembled ligase ribozymes has catalytic activity, due to the presence of disabling mutations. Further efforts to improve the polymerase will need to select more strongly for the accurate synthesis of complex RNAs to enable the generalized replication of functional RNAs.

          Source

          © Copyright Original Source


          So it doesn't appear to make a full copy of itself, and the fidelity is poor.

          Source: PNAS

          Thus, while the improved polymerase ribozyme has the ability to synthesize large complex RNAs, including a three-fragment form of its own ancestor, the fidelity of synthesis is insufficient to enable a significant fraction of the products to retain the information necessary for catalytic function.

          © Copyright Original Source


          Sounds like the resulting products don't work!

          Blessings,
          Lee
          "What I pray of you is, to keep your eye upon Him, for that is everything. Do you say, 'How am I to keep my eye on Him?' I reply, keep your eye off everything else, and you will soon see Him. All depends on the eye of faith being kept on Him. How simple it is!" (J.B. Stoney)

          Comment


          • #6
            Originally posted by lee_merrill View Post
            Sounds like the resulting products don't work!]
            If you paid as careful attention to the original source you quoted as you did to these papers, you'd recognize that, even though they have not yet succeeded in making a self-replicating RNA, they've long since cleared the hurdle of "no polymerase has ever been constructed, or likely will be constructed*, that could replicate more than a small fraction of itself."

            Your original source lied. Admit it and move on.

            And maybe thing twice before using them in the future.


            * I like how they just decree that something we only started to study within the past 15 years or so is probably impossible. This is exactly the sort of science stopper that Rogue keeps saying it is, and Lee keeps denying.
            "Any sufficiently advanced stupidity is indistinguishable from trolling."

            Comment


            • #7
              Originally posted by TheLurch View Post
              If you paid as careful attention to the original source you quoted as you did to these papers, you'd recognize that, even though they have not yet succeeded in making a self-replicating RNA, they've long since cleared the hurdle of "no polymerase has ever been constructed, or likely will be constructed*, that could replicate more than a small fraction of itself."
              Well, I haven't been able to read the first two papers, but the third paper does not do what you claimed for it. That's Tour's caution about origin-of-life research, that claims have been inflated.

              Blessings,
              Lee
              "What I pray of you is, to keep your eye upon Him, for that is everything. Do you say, 'How am I to keep my eye on Him?' I reply, keep your eye off everything else, and you will soon see Him. All depends on the eye of faith being kept on Him. How simple it is!" (J.B. Stoney)

              Comment


              • #8
                Originally posted by lee_merrill View Post
                Well, I haven't been able to read the first two papers, but the third paper does not do what you claimed for it. That's Tour's caution about origin-of-life research, that claims have been inflated.
                It does do what i claimed for it. It can copy up to 125 nucleotide long sequences (possibly longer, wasn't tested in the paper if i recall).

                In any case, none of your nitpicking gets around the claim that these molecules cannot copy even a tiny fraction of themselves, and it's unlikely they ever will. That is the claim at issue here. I don't have to show a perfectly functioning self replicator to show that that is false.
                "Any sufficiently advanced stupidity is indistinguishable from trolling."

                Comment


                • #9
                  Originally posted by TheLurch View Post
                  It does do what i claimed for it. It can copy up to 125 nucleotide long sequences (possibly longer, wasn't tested in the paper if i recall).
                  I got the papers mixed up in my reply, it was the first paper that I could access. But the third paper doesn't sound like it's copying itself. And are they giving the ribozyme a helping hand by appending special sequences to what is being copied?

                  Blessings,
                  Lee
                  "What I pray of you is, to keep your eye upon Him, for that is everything. Do you say, 'How am I to keep my eye on Him?' I reply, keep your eye off everything else, and you will soon see Him. All depends on the eye of faith being kept on Him. How simple it is!" (J.B. Stoney)

                  Comment


                  • #10
                    Originally posted by lee_merrill View Post
                    I got the papers mixed up in my reply, it was the first paper that I could access. But the third paper doesn't sound like it's copying itself. And are they giving the ribozyme a helping hand by appending special sequences to what is being copied?

                    Blessings,
                    Lee
                    You have gotten everything mixed up ever since you started posting your religious ID agenda without real science.

                    By the way the RNA world of Viruses have functioned very well since the very beginning age of abiogenesis, and metabolize carbohydrates.

                    Glendower: I can call spirits from the vasty deep.
                    Hotspur: Why, so can I, or so can any man;
                    But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

                    go with the flow the river knows . . .

                    Frank

                    I do not know, therefore everything is in pencil.

                    Comment


                    • #11
                      Originally posted by lee_merrill View Post
                      I got the papers mixed up in my reply, it was the first paper that I could access. But the third paper doesn't sound like it's copying itself. And are they giving the ribozyme a helping hand by appending special sequences to what is being copied?
                      It can copy parts of a molecule that contains some of its own sequence.
                      "Any sufficiently advanced stupidity is indistinguishable from trolling."

                      Comment


                      • #12
                        Originally posted by TheLurch View Post
                        It can copy parts of a molecule that contains some of its own sequence.
                        Well, that would not be copying itself, then. And are they able to copy folded ribozymes?

                        Blessings,
                        Lee
                        "What I pray of you is, to keep your eye upon Him, for that is everything. Do you say, 'How am I to keep my eye on Him?' I reply, keep your eye off everything else, and you will soon see Him. All depends on the eye of faith being kept on Him. How simple it is!" (J.B. Stoney)

                        Comment


                        • #13
                          Originally posted by lee_merrill View Post
                          Well, that would not be copying itself, then. And are they able to copy folded ribozymes?
                          I think we may have a semantic problem. When biologist are talking bout "copying itself" in this context, it simply means a molecule with the same sequence, not actually copying the same physical molecule.
                          "Any sufficiently advanced stupidity is indistinguishable from trolling."

                          Comment


                          • #14
                            Originally posted by TheLurch View Post
                            I think we may have a semantic problem. When biologist are talking bout "copying itself" in this context, it simply means a molecule with the same sequence, not actually copying the same physical molecule.
                            Copying a copy would be fine, but that's not what you indicated. And can folded ribozymes be copied?

                            Blessings,
                            Lee
                            "What I pray of you is, to keep your eye upon Him, for that is everything. Do you say, 'How am I to keep my eye on Him?' I reply, keep your eye off everything else, and you will soon see Him. All depends on the eye of faith being kept on Him. How simple it is!" (J.B. Stoney)

                            Comment


                            • #15
                              Originally posted by lee_merrill View Post
                              Copying a copy would be fine, but that's not what you indicated. And can folded ribozymes be copied?
                              Don't know about how much secondary structure these things can have before replication fails - would have to look into it.

                              But it's clear that these can copy a substantial portion of their own sequence as part of a larger sequence. Which again, makes the original statement false.
                              "Any sufficiently advanced stupidity is indistinguishable from trolling."

                              Comment

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