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Advances in the science of abiogenesis

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  • Advances in the science of abiogenesis

    This thread will review scientific articles on the advancements in the science of abiogenesis

    The first article concerns research in the mechanism for the formation of RNA.

    [cite=https://www.wired.com/2009/05/ribonucleotides/]
    LIFE'S FIRST SPARK RE-CREATED IN THE LABORATORY

    A fundamental but elusive step in the early evolution of life on Earth has been replicated in a laboratory.

    Researchers synthesized the basic ingredients of RNA, a molecule from which the simplest self-replicating structures are made. Until now, they couldn't explain how these ingredients might have formed.

    "It's like molecular choreography, where the molecules choreograph their own behavior," said organic chemist John Sutherland of the University of Manchester, co-author of a study in Nature Wednesday.

    RNA is now found in living cells, where it carries information between genes and protein-manufacturing cellular components. Scientists think RNA existed early in Earth's history, providing a necessary intermediate platform between pre-biotic chemicals and DNA, its double-stranded, more-stable descendant.

    However, though researchers have been able to show how RNA's component molecules, called ribonucleotides, could assemble into RNA, their many attempts to synthesize these ribonucleotides have failed. No matter how they combined the ingredients — a sugar, a phosphate, and one of four different nitrogenous molecules, or nucleobases — ribonucleotides just wouldn't form.

    Sutherland's team took a different approach in what Harvard molecular biologist Jack Szostak called a "synthetic tour de force" in an accompanying commentary in Nature.

    "By changing the way we mix the ingredients together, we managed to make ribonucleotides," said Sutherland. "The chemistry works very effectively from simple precursors, and the conditions required are not distinct from what one might imagine took place on the early Earth."

    . . .

    At each stage of the cycle, the resulting molecules were more complex. At the final stage, Sutherland's team added phosphate. "Remarkably, it transformed into the ribonucleotide!" said Sutherland.

    "Ribonucleotides are simply an expression of the fundamental principles of organic chemistry," said Sutherland. "They're doing it unwittingly. The instructions for them to do it are inherent in the structure of the precursor materials. And if they can self-assemble so easily, perhaps they shouldn't be viewed as complicated."


    *Citations: Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions Matthew W. Powner, Beatrice Gerland & John D. Sutherland. Nature, Vol. 460, May 13, 2009.

    *"Systems chemistry on early Earth." By Jack W. Szostak. **Nature, Vol. 460, May 13, 2009.
    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.

  • #2
    Though the sugars need to be all left-handed (or all right-handed), my guess is that they weren't...

    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


    • #3
      Originally posted by lee_merrill View Post
      Though the sugars need to be all left-handed (or all right-handed), my guess is that they weren't...

      Blessings,
      Lee
      Source: https://phys.org/news/2012-01-scientists-clue-chemical-life.html#jCp



      Scientists discover new clue to the chemical origins of life
      January 24, 2012, University of York
      Organic chemists at the University of York have made a significant advance towards establishing the origin of the carbohydrates (sugars) that form the building blocks of life.

      A team led by Dr Paul Clarke in the Department of Chemistry at York have re-created a process which could have occurred in the prebiotic world.

      Working with colleagues at the University of Nottingham, they have made the first step towards showing how simple sugars –threose and erythrose—developed. The research is published in Organic & Biomolecular Chemistry.

      All biological molecules have an ability to exist as left-handed forms or right-handed forms. All sugars in biology are made up of the right-handed form of molecules and yet all the amino acids that make up the peptides and proteins are made up of the left-handed form.

      The researchers found using simple left-handed amino acids to catalyse the formation of sugars resulted in the production of predominately right-handed form of sugars. It could explain how carbohydrates originated and why the right-handed form dominates in nature.

      Dr Clarke said: "There are a lot of fundamental questions about the origins of life and many people think they are questions about biology. But for life to have evolved, you have to have a moment when non-living things become living -- everything up to that point is chemistry.

      "We are trying to understand the chemical origins of life. One of the interesting questions is where carbohydrates come from because they are the building blocks of DNA and RNA. What we have achieved is the first step on that pathway to show how simple sugars –threose and erythrose—originated. We generated these sugars from a very simple set of materials that most scientists believe were around at the time that life began."



      Read more at: https://phys.org/news/2012-01-scient...-life.html#jCp

      © Copyright Original Source

      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


      • #4
        The basic goals of science concerning Abogenesis at present focus mostly on are: (1) The natural chemical evolution of inorganic amino acids to RNA. (2) The natural chemical evolution of inorganic phosphates to functional organic phosphates that are capable of energy storage and transfer independent outside energy sources, such as the ADP > ATP energy organic energy transfer process. (3) The environment where abiogenesis took place with sufficient energy, and chemistry suitable for abiogenesis. The three dominant environments that meet this criteria are: (1) Alkaline thermal vents on mid-ocean ridges. (2) Terrestrial environments such as volcanic vents clay volcanic vents, or coastal environments. (3) Combinations of the first such as where mid-ocean ridges come to the surface as in Iceland.

        I favor the alkaline thermal mid-ocean ridge vents. I will give my reason with scientific references in future posts.
        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
          Source: phys.org

          The researchers found using simple left-handed amino acids to catalyse the formation of sugars resulted in the production of predominately right-handed form of sugars.

          © Copyright Original Source


          So they started with left-handed amino acids for this step, I would still contend that in their starting experiment they did not generate all left-handed amino acids. Note also that even with loading the deck, they couldn't generate all right-handed sugars, which is a requirement for life, AFAIK.

          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
            Source: phys.org

            The researchers found using simple left-handed amino acids to catalyse the formation of sugars resulted in the production of predominately right-handed form of sugars.

            © Copyright Original Source


            So they started with left-handed amino acids for this step, I would still contend that in their starting experiment they did not generate all left-handed amino acids. Note also that even with loading the deck, they couldn't generate all right-handed sugars, which is a requirement for life, AFAIK.

            Blessings,
            Lee
            I do not believe it is necessary to develop all right-handed sugar nor left-handed amino acids. Thee simply are left-handed amino acids available that will react to produce right handed sugars to form RNA as the reference indicated.

            From the reference cited: "The researchers found using simple left-handed amino acids to catalyse the formation of sugars resulted in the production of predominately right-handed form of sugars. It could explain how carbohydrates originated and why the right-handed form dominates in nature."
            Last edited by shunyadragon; 10-15-2018, 10:45 AM.
            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


            • #7
              Originally posted by shunyadragon View Post
              I do not believe it is necessary to develop all right-handed sugar nor left-handed amino acids. Thee simply are left-handed amino acids available that will react to produce right handed sugars to form RNA as the reference indicated.
              Well, mostly right-handed sugars, correct? And RNA was not formed, just sugars:

              Source: phys.org

              What we have achieved is the first step on that pathway to show how simple sugars –threose and erythrose—originated.

              © Copyright Original Source



              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, mostly right-handed sugars, correct? And RNA was not formed, just sugars:

                Source: phys.org

                What we have achieved is the first step on that pathway to show how simple sugars –threose and erythrose—originated.

                © Copyright Original Source



                Blessings,
                Lee
                This reference only involve the formation of the right-handed sugars by left-handed amino acids. This was in response to your question. The previous reference involved the natural formation of RNA.
                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


                • #9
                  Originally posted by shunyadragon View Post
                  This reference only involve the formation of the right-handed sugars by left-handed amino acids. This was in response to your question. The previous reference involved the natural formation of RNA.
                  They formed ribonucleotides, that would not be RNA.

                  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
                    They formed ribonucleotides, that would not be RNA.

                    Blessings,
                    Lee
                    correct . . .

                    "Researchers synthesized the basic ingredients of RNA, a molecule from which the simplest self-replicating structures are made. Until now, they couldn't explain how these ingredients might have formed."

                    more to follow . . .
                    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
                      Source: https://www.sciencedaily.com/releases/2018/11/181120125822.htm


                      Amino acid chains spontaneously build up in typical early earth conditions recreated in labs.
                      Could yesterday's Earth contain clues for making tomorrow's medicines?
                      Izabela Sibilska, Yu Feng, Lingjun Li, John Yin. Trimetaphosphate Activates Prebiotic Peptide Synthesis across a Wide Range of Temperature and pH. Origins of Life and Evolution of Biospheres, 2018; 48

                      Research abstract:-
                      The biochemical activation of amino acids by adenosine triphosphate (ATP) drives the synthesis of proteins that are essential for all life. On the early Earth, before the emergence of cellular life, the chemical condensation of amino acids to form prebiotic peptides or proteins may have been activated by inorganic polyphosphates, such as tri metaphosphate (TP). Plausible volcanic and other potential sources of TP are known, and TP readily activates amino acids for peptide synthesis. But de novo peptide synthesis also depends on pH, temperature, and processes of solvent drying, which together define a varied range of potential activating conditions. Although we cannot replay the tape of life on Earth, we can examine how activator, temperature, acidity and other conditions may have collectively shaped its prebiotic evolution. Here, reactions of two simple amino acids, glycine and alanine, were tested, with or without TP, over a wide range of temperature (0-100 °C) and acidity (pH 1-12), while open to the atmosphere. After 24 h, products were analyzed by HPLC and mass spectrometry. In the absence of TP, glycine and alanine readily formed peptides under harsh near-boiling temperatures, extremes of pH, and within dry solid residues. In the presence of TP, however, peptides arose over a much wider range of conditions, including ambient temperature, neutral pH, and in water. These results show how polyphosphates such as TP may have enabled the transition of peptide synthesis from harsh to mild early Earth environments, setting the stage for the emergence of more complex prebiotic chemistries.

                      © Copyright Original Source

                      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


                      • #12
                        Self Replicating RNA emerges in the lab through directed evolution.

                        Source: https://www.cell.com/cell-chemical-biology/fulltext/S1074-5521(13)00426-2



                        An RNA enzyme has been developed that catalyzes the joining of oligonucleotide substrates to form additional copies of itself, undergoing self-replication with exponential growth. The enzyme also can cross-replicate with a partner enzyme, resulting in their mutual exponential growth and enabling self-sustained Darwinian evolution. The opportunity for inventive evolution within this synthetic genetic system depends on the diversity of the evolving population, which is limited by the catalytic efficiency of the enzyme. Directed evolution was used to improve the efficiency of the enzyme and increase its exponential growth rate to 0.14 min−1, corresponding to a doubling time of 5 min. This is close to the limit of 0.21 min−1imposed by the rate of product release, but sufficient to enable more than 80 logs of growth per day.

                        To enable the propagation of genetic information, the self-replicating RNA ligase has been converted to a cross-replication format whereby two RNA enzymes catalyze each other’s synthesis from a total of four component substrates ( Kim and Joyce, 2004). Information is transmitted between the parent and progeny enzymes through two regions of Watson-Crick pairing, each of which may contain many possible sequences. Recombination can occur between these two regions, resulting in novel variants that compete for utilization of the oligonucleotide substrates. Those variants that have faster exponential growth rates enjoy a selective advantage, resulting in the self-sustained Darwinian evolution of the fittest replicators ( Lincoln and Joyce, 2009).

                        © Copyright Original Source

                        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


                        • #13
                          Source: https://www.sciencenews.org/article/droplets-acid-molecules-may-have-helped-kick-start-life-earth?utm_source=email&utm_medium=email&utm_campaign=latest-newsletter-v2&utm_source=Latest_Headlines&utm_medium=email&utm_campaign=Latest_Headlines



                          Droplets of these simple molecules may have helped kick-start life on Earth

                          Small blobs that break apart and reform can host protein and RNA

                          A new study shows that a simple class of molecules called alpha hydroxy acids forms microdroplets when dried and rewetted, as could have taken place at the edges of water sources. These cell-sized compartments can trap RNA, and can merge and break apart — behavior that could have encouraged inanimate molecules in the primordial soup to give rise to life, researchers report July 22 in the Proceedings of the National Academy of Sciences.

                          Besides giving clues to how life may have gotten started on the planet, the work might have additional applications in both medicine and the search for extraterrestrial life.

                          Present-day biology relies on cells to concentrate nutrients and protect genetic information, so many scientists think that compartments could have been important for life to begin. But no one knows whether the first microenclosures on Earth were related to modern cells.

                          “The early Earth was certainly a messy place chemically,” with nonbiological molecules such as alpha hydroxy acids potentially having roles in the emergence of life alongside biomolecules like RNA and their precursors, says biochemist Tony Jia of Tokyo Institute of Technology’s Earth-Life Science Institute.

                          Jia’s team focused on mixtures of alpha hydroxy acids, some of which are common in skin-care cosmetics. Though not as prominent as their chemical relatives amino acids, alpha hydroxy acids are plausible players in origin-of-life happenings because they frequently show up in meteorites as well as in experiments mimicking early Earth chemistry.

                          In 2018, a team led by geochemists Kuhan Chandru of the Earth-Life Science Institute and the National University of Malaysia at Bangi and H. James Cleaves, also of the Earth-Life Science Institute, demonstrated that, just though drying, alpha hydroxy acids form repeating chains of molecules called polymers. In the new study, the pair along with Jia and their colleagues found that rewetting the polymers led to the formation of microdroplets about the same diameter as modern red blood cells or cheek cells.

                          Prior studies have shown that simple molecules can form droplets (SN: 4/15/17, p. 11). The new work goes further in showing “that possibly prebiotically relevant molecules can form droplets,” says artificial cell expert Dora Tang of the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, who wasn’t involved with the work.

                          In the lab, the team demonstrated that the droplets could trap and host molecules essential to life as we know it, such as RNA. The researchers also observed that a protein retained its function within the droplets and that fatty acids could assemble around the droplets.

                          Still, those findings don’t mean the microdroplets were Earth’s first cells or ancestors of them, Chandru cautions. Instead, he suggests that the droplets could have helped reactions along in emerging biochemical systems in the lead-up to the origin of life.

                          Though the team’s focus is origin-of-life studies, Jia points out that these microdroplets could potentially be engineered to deliver medications. The researchers note in their study that they may apply for a patent related to the work within the next year but have not specified an application.

                          The new research may also hold an important lesson for the search for extraterrestrial life (SN: 4/30/16, p. 28). “We need to not only focus on detection of modern biomolecules and their precursors, but also other relevant nonbiomolecules” that, like alpha hydroxy acids, might have played supporting roles in the emergence of life, on Earth or elsewhere, Jia says.

                          Citations
                          T. Jia et al. Membraneless polyester microdroplets as primordial compartments at the origins of life. Proceedings of the National Academy of Sciences. Published online July 22, 2019. doi:10.1073/pnas.1902336116.

                          K. Chandru et al. Simple prebiotic synthesis of high diversity dynamic combinatorial polyester libraries. Communications Chemistry. Vol. 1, May 2018. doi:10.1038/s42004-018-0031-1.

                          Further Reading
                          E. Conover. Life on Earth may have begun as dividing droplets. Science News. Vol. 191, April 15, 2017, p. 11.

                          T.H. Saey. Will we know extraterrestrial life when we see it? Science News. Vol. 189, April 30, 2016, p. 28.

                          © Copyright Original Source

                          Last edited by shunyadragon; 07-23-2019, 07:59 PM.
                          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


                          • #14
                            Originally posted by shunyadragon View Post
                            Self Replicating RNA emerges in the lab through directed evolution.

                            Source: https://www.cell.com/cell-chemical-biology/fulltext/S1074-5521(13)00426-2



                            An RNA enzyme has been developed that catalyzes the joining of oligonucleotide substrates to form additional copies of itself, undergoing self-replication with exponential growth. The enzyme also can cross-replicate with a partner enzyme, resulting in their mutual exponential growth and enabling self-sustained Darwinian evolution. The opportunity for inventive evolution within this synthetic genetic system depends on the diversity of the evolving population, which is limited by the catalytic efficiency of the enzyme. Directed evolution was used to improve the efficiency of the enzyme and increase its exponential growth rate to 0.14 min−1, corresponding to a doubling time of 5 min. This is close to the limit of 0.21 min−1imposed by the rate of product release, but sufficient to enable more than 80 logs of growth per day.

                            To enable the propagation of genetic information, the self-replicating RNA ligase has been converted to a cross-replication format whereby two RNA enzymes catalyze each other’s synthesis from a total of four component substrates ( Kim and Joyce, 2004). Information is transmitted between the parent and progeny enzymes through two regions of Watson-Crick pairing, each of which may contain many possible sequences. Recombination can occur between these two regions, resulting in novel variants that compete for utilization of the oligonucleotide substrates. Those variants that have faster exponential growth rates enjoy a selective advantage, resulting in the self-sustained Darwinian evolution of the fittest replicators ( Lincoln and Joyce, 2009).

                            © Copyright Original Source

                            *emphasis mine

                            So, are they trying to advance Intelligent Design or just proving that retro-engineering is a thing?

                            But more importantly, has it been replicated? These are fairly old papers and didn't seem to create much of a stir at the time - what has been done since?

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                            Comment


                            • #15
                              Originally posted by Teallaura View Post
                              *emphasis mine

                              So, are they trying to advance Intelligent Design or just proving that retro-engineering is a thing?
                              Directed engineering is not Intelligent Design. It just means they were able to do it in the lab through directed engineering,

                              But more importantly, has it been replicated? These are fairly old papers and didn't seem to create much of a stir at the time - what has been done since?
                              Good question.

                              This is interesting more recent related research:

                              Source: https://elifesciences.org/articles/35255



                              Ribozyme-catalysed RNA synthesis using triplet building blocks

                              Abstract
                              RNA-catalyzed RNA replication is widely believed to have supported a primordial biology. However, RNA catalysis is dependent upon RNA folding, and this yields structures that can block replication of such RNAs. To address this apparent paradox, we have re-examined the building blocks used for RNA replication. We report RNA-catalysed RNA synthesis on structured templates when using trinucleotide triphosphates (triplets) as substrates, catalysed by a general and accurate triplet polymerase ribozyme that emerged from in vitro evolution as a mutualistic RNA heterodimer. The triplets cooperatively invaded and unraveled even highly stable RNA secondary structures, and support non-canonical primer-free and bidirectional modes of RNA synthesis and replication. Triplet substrates thus resolve a central incongruity of RNA replication, and here allow the ribozyme to synthesise its own catalytic subunit ‘+’ and ‘–’ strands in segments and assemble them into a new active ribozyme.

                              https://doi.org/10.7554/eLife.35255.001

                              Introduction

                              The premise that some RNA sequences can catalyse and template their own replication - reciprocally synthesizing their own ‘+’ and ‘–’ strands - underpins current thinking about early genetic systems (Crick, 1968; Orgel, 1968; Szostak et al., 2001). Any ancient ribozyme with such RNA replicase capability seems to be lost, but efforts are ongoing to recreate RNA self-replication in the laboratory (Martin et al., 2015) as a critical test of the ‘RNA world’ hypothesis (Gilbert, 1986). Early on, derivatives of naturally occurring self-splicing introns (Doudna et al., 1991; Green and Szostak, 1992; Hayden and Lehman, 2006) as well as later in vitro evolved ligase ribozymes (Lincoln and Joyce, 2009; Sczepanski and Joyce, 2014) were shown to be able to assemble one of their own strands from cognate constituent RNA segments. However, a critical drawback of such systems is their need for specific preformed building blocks of at least eight nucleotides (nt) average length, limiting their potential for open-ended evolution, and precluding their replication from pools of random-sequence oligonucleotide substrates (Green and Szostak, 1992; Doudna et al., 1993).

                              In a contrasting approach, RNA polymerase ribozymes (RPRs) have been developed that can use general monomer building blocks (ribonucleoside 5’ triphosphates (NTPs)) in RNA-templated RNA synthesis (Johnston et al., 2001; Zaher and Unrau, 2007; Wochner et al., 2011; Attwater et al., 2013b; Horning and Joyce, 2016), akin to the activity of modern proteinaceous polymerases. However, even the most highly-evolved RPRs (Horning and Joyce, 2016) 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 (Boza et al., 2014). This ostensible ‘structure vs. replication’ paradox would have placed stringent probability constraints on the emergence of an RNA replicase and generally impeded the ability of RNA to function as an early genetic polymer.

                              We wondered whether this paradox might be avoided through a re-consideration of plausible building blocks for early RNA replication. Models of non-enzymatic polymerisation of all four activated ribonucleotides – the presumed source of the first RNA sequences – yield pools of di-, tri- and tetranucleotide etc. length oligonucleotides (in decreasing abundance) dominating the population alongside longer products (Monnard et al., 2003). Here, we have examined whether substrates of such lengths can support RNA-catalyzed RNA replication, by developing a ribozyme capable of iterative templated ligation of 5’-triphosphorylated RNA trinucleotides (henceforth called triplets). This heterodimeric triplet polymerase ribozyme demonstrated a striking capacity to copy a wide range of RNA sequences, including highly structured, previously intractable RNA templates, as well as its own catalytic domain and encoding template in segments. Its characterization revealed emergent properties of triplet-based RNA synthesis, including cooperative invasion and unraveling of stable RNA structures by triplet substrates, bi-directional (both 5’−3’ and 3’−5’) and primer-free (triplet-initiated) RNA synthesis, and fidelity augmented by systemic properties of the random triplet pools.

                              Results

                              In vitro evolution of triplet polymerase activity

                              We set out to explore the potential of short RNA oligonucleotides as substrates for RNA-catalyzed RNA replication. To do this, we required a ribozyme capable of general, iterative RNA-templated oligonucleotide ligation. Previously-described RNA polymerase ribozymes such as the ‘Z’ RPR (Wochner et al., 2011) can use NTPs to iteratively extend a primer hybridized to an RNA template, but do not accommodate oligonucleotides bound downstream of the primer or accept them as substrates. However, we detected a weak templated ligation activity in a truncated version of the Z RPR comprising its catalytic core domain (Zcore) (Figure 1a), which supported incorporation of oligonucleotide substrates as short as three nt (Figure 1—figure supplement 1) when incubated in the eutectic phase of water ice (Attwater et al., 2010; Mutschler et al., 2015).

                              © Copyright Original Source

                              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

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