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RNA that replicates itself

The scientists synthesized for the first time RNA enzymes that can replicate themselves without needing the help of proteins or other cellular components. RNA is a nucleotide chain that probably preceded DNA, so it almost certainly preceded it on the way from inanimate to living

A repeating pattern as in RNA. Illustration: The Scripts Institute
A repeating pattern as in RNA. Illustration: The Scripts Institute

A pair of scientists at the Scripps Institute succeeded in creating RNA enzymes capable of endlessly replicating themselves. Is this the simplest - and most ancient - form of life?

One of the recurring questions is the question of the beginning of life. How was life first created on earth? The answer that has always been given has focused on molecules that are able to make copies of themselves. Such molecules fulfill the initial condition for heredity, a feature that characterizes all living systems. Now, a pair of scientists from the Scripps Research Institute have taken a big step towards answering that question. The scientists synthesized for the first time RNA enzymes that can replicate themselves without needing the help of proteins or other cellular components, and the process continues over and over again, for an unlimited period of time.

In the modern world, DNA carries the sequence of genetic information in developed organisms, while RNA is responsible for transferring the information from the DNA to the ribosomes, which act according to the instructions contained in the information and produce new proteins. One important theory regarding the origin of life, called the 'RNA world', assumes that because RNA can function as both a gene and an enzyme, it is possible that RNA existed before DNA and proteins, as the primitive molecule of life. At the same time, the transcription process of a molecule containing genetic material, which is considered a basic requirement of life, is extremely complicated and requires the involvement of many proteins and other units in the cell.

For many years, researchers wondered if there might be a simpler way to replicate RNA that RNA itself could do. Joyce's laboratory and others have already taken several steps in this direction, but the person who succeeded in showing that RNA replication can continue for a long time - that is, that the replication products will also succeed in replicating themselves - has not yet arisen.

Several years after Tracy Lincoln arrived at the Scripps Institute from Jamaica to work on her PhD, she began to explore the idea of ​​replication using RNA, side by side with her supervisor, Professor Gerald Joyce. Their work began with the method of 'forced adaptation', also known as 'evolution in vitro'. Their goal was to take one of the RNA enzymes already existing in the laboratory, which was able to perform the basic chemical operation of replication, and improve it to the point where it could perform efficient and constant self-replication.

Lincoln synthesized in the laboratory a large population of slightly different RNA enzymes, and subjected them to evolution in vitro in order to obtain the variants that were particularly suitable for joining pieces of RNA. Ultimately, this process allowed the group to isolate a version of the original enzyme that had evolved and is a very efficient replicator. The improved enzyme fulfills the main requirement: to undergo continuous replication.
The replication system actually involves two enzymes. Each of them consists of two subunits, and functions as a catalyst that connects the other two subunits. The replication process is circular: the first enzyme binds the two subunits that make up the second enzyme, and joins them together to form a new copy of the second enzyme. The second enzyme then similarly binds the two subunits that make up the first enzyme. In this way, the two enzymes assemble each other in a process called cross replication. For the process to continue indefinitely, only a small initial amount of the two enzymes and a constant supply of the subunits are needed.

"This is the only case outside of biology where molecular information has become eternal," Joyce said.
But this alone was not enough for the researchers. The two created a variety of enzyme pairs with similar abilities. They mixed a dozen cross-pairs of different replicating enzymes, along with all their subunits, and allowed them to compete against each other in a molecular test to determine which one was the most capable of multiplying in vitro. Most of the time, the enzymes replicated themselves correctly, but occasionally one enzyme or another made a mistake and bound a subunit that belonged to one of the other replicating enzymes. When such a 'mutation' occurred, the newly formed enzymes were also able to continue self-replication, and the fittest replicators took over the test tube. "For me, this is actually the biggest result," Joyce said.

The research shows that the system can support molecular information and transfer it to future generations in a hereditary manner, thus leading to the creation of variations of itself in a manner reminiscent of Darwinian evolution. Thus, says Lincoln, "what we have is not alive, but we have been able to show that it has certain life-like properties, and that has been most interesting."

The real value of the work, according to Joyce, lies in the level of basic research. "What we found may be relevant to the way life began, at that key point where Darwinian evolution began." At the same time, he is quick to point out that although the system of replicating RNA enzymes possesses certain properties of life, it does not constitute a form of life in itself.

We will never be able to accurately recreate the true origin of life, so we only have to answer the question of whether it will ever be possible to create life in a laboratory. The answer to this may, of course, answer the original question: what did life look like in its earliest form. "We're not trying to turn back time," Lincoln said, "but it might explain how we should begin to understand the emergence of life in the lab."

Joyce says that only when a system is developed in the laboratory, capable of undergoing evolution to acquire new abilities on its own, then it will be called an animal. "We're knocking on that door," he said, "but of course we haven't gotten there yet."

The subunits in the enzymes assembled by the group contain many nucleotides, each of them, and are therefore relatively complicated. It is hard to assume that they could have been found sailing in the ancient sea. But even though the original building blocks were probably simpler, this work finally shows that an RNA-based life form is indeed possible. This information will advance the future research concerning the issue of the RNA world, and hopefully will allow us, in the end, to establish the origin of life on earth.
The study was published on January 8, 2009, in the journal Science Express.

Source: http://www.scripps.edu/newsandviews/e_20090112/joyce.html

47 תגובות

  1. someone:
    I don't know why you call theoretical.
    These things were actually done.
    In general - regarding the term theoretical - it is appropriate that everyone internalize the fact that there is nothing more practical than a good theory.

  2. Interesting. Although the name of the experiment and who performed it are not specified. It sounds more theoretical. The same goes for the amino acids. But this is already progress.

  3. And the point has changed again...

    You are welcome to check about the experiment. But since all your 'references' have so far been taken from Wikipedia, it is interesting to note that you choose very selectively what to believe and what not.

  4. What I found is listed there-".[12] Experiments conducted later showed that the other RNA and DNA nucleobases could be obtained through simulated prebiotic chemistry with a reducing atmosphere.[13]"-it is not clear exactly which experiment and how. Although it is worth checking.

  5. someone,

    Of course, there is a chance that the recent Yuri-Miller experiment was contaminated, but this does not seem likely. If it was contaminated, we should have found much more amino acids and other chemical substances there. As it stands now, the results of the experiment stand firm.

    As for the experiment that demonstrated the creation of all five nucleotides of DNA and RNA all over the planet, you can find the reference on Wikipedia, similar to the reference you provided. You just have to go to the page about the Yuri-Miller experiment in English.
    http://en.wikipedia.org/wiki/Miller-Urey_experiment

    The information on Wikipedia on this subject came from the book, Origins of Prebiological Systems and of Their Molecular Matrices, which contains articles by Haldane, Ofarin, Sagan and other researchers, some of the most important who studied the issue of the beginning of life and conducted in-depth experiments in the field.

    In the end, none of this matters. It doesn't matter either because you don't really argue, but rush to change your 'point' every time your claims are contradicted. But even the new point you chose does not pass any logical test. If there are scientists who claim that they will soon be able to create synthetic life, then they are based on a very simple definition of life. The new life form will most likely be based on RNA or DNA that replicates itself, and as long as it is supplied with nucleotides, it will continue to replicate itself and undergo evolution.

    Even if scientists did not succeed in creating nucleotides (and they do), it does not change the fact that such a life form can be created. So what's your point now?

  6. Michael. I'm asking for the last time, give a reference for your words. You claim that they know how to create all the nucleotides without exception, as well as the amino acids? Please, do you have a chance to show this. Just throw in the air "they have already created everything" I know too

  7. Someone from somewhere:
    Am I just overwhelmed?
    Don't you understand that they know how to create all the necessary ingredients in different ways?
    There is nothing among the chemical things - neither nucleotides nor amino acids - that cannot be produced synthetically and for that matter it does not matter at all if they were obtained in the Yuri Miller experiment which was not at all intended to find a way to produce them but to create an Earth-like environment where they are formed randomly and not in a form targeted

  8. interesting,

    "The experiment imitated only a small part of the conditions that might have existed in the DHA, and for a short period of time of only one week. For comparison, it is currently estimated that the first life originated in a time period of between a hundred and a million years, in a huge ocean. What do you think, because you will compare an ocean rich in reactions, for a million years, to an experiment in which a small jar was conducted in only one week?" - I don't think it belongs to the size. But in any case, my point is that how can scientists announce that in a few years they have created artificial life, if they don't have Still on all the cornerstones?

    "But even if you insist on the comparison, let's say. In more advanced experiments (in 1961), researchers proved that when you simulate a repeating environment over DNA, you get all five nucleotides of DNA and RNA. *Everyone*. "-Where did you see this? I would appreciate a link. This is the first time I've heard of this.

    Want more?

    In 2008, scientists tested test tubes from Miller's other experiments with modern and more accurate tools, and discovered that he had missed several amino acids. It turns out that in some of his experiments, which simulated ancient volcanic eruptions, no less than 22 amino acids were formed." made amino acids.

  9. Someone from somewhere:
    We are not confused.
    You are just confusing.
    In most of your responses you talked about the creation of nucleotides in general and it is also a fact that you did not answer in a shameful way as you did now when I showed you that cytosine was created in 1903.
    It just took you a while to come up with what you were talking about in retrospect and that's why you're only saying it now.
    Good. So it turns out that what you just said is also wrong - as Roy showed you.
    I suggest that you reinvent the past one more time and this time in such a way that all the answers you have received so far will again become irrelevant

  10. someone,

    You are talking about a specific experiment called the 'Yuri-Miller experiment', which was conducted over fifty years ago. This experiment was one of the first to try to recreate some of the conditions that prevailed on Earth billions of years ago.

    The simple truth is that in that experiment no nucleotides or all the amino acids were indeed formed, but this is not at all surprising. The experiment imitated only a small part of the conditions that might have existed in DHA, and for a short period of time of only one week. For comparison, it is currently estimated that the first life originated in a time period of between a hundred and a million years, in a huge ocean. What do you think, because you will compare an ocean rich in reactions, for a million years, to an experiment with a small jar conducted in just one week?

    But even if you insist on the comparison, come on. In more advanced experiments (in 1961), researchers proved that when simulating a repeating environment over DNA, you get all five nucleotides of DNA and RNA. *Everyone*.

    Want more?

    In 2008, scientists tested test tubes from Miller's other experiments with modern and more accurate tools, and discovered that he had missed several amino acids. It turns out that in some of his experiments, which simulated ancient volcanic eruptions, no fewer than 22 amino acids were formed.

    http://en.wikipedia.org/wiki/Miller–Urey_experiment

    It's good to know the facts before talking.

    Roy.

  11. To the confused point and Michael-

    Here's what I said at the very beginning - "never in any natural environment have nucleotides been found. Even in an experiment, I think only one was created." ". with an emphasis on *every*. And for those who cannot find it on wiki-"in Miller-Urey-type experiments in which they tried to produce organic substances under laboratory conditions, no nucleotides were formed."

    Did you hear? Not *all* the nucleotides were created.
    And also - "2% of the carbon content in the experiment turned into amino acids - 3 out of the 20 amino acids that appear in living things. The amino acid that formed in the greatest amount was glycine" - did you hear? Not all amino acids were formed. They cannot ignore these serious problems. I hope you will not come back again on yourselves and claim that they were indeed created.

  12. Reader and point:
    In my opinion, "someone" shows signs of a believing Jew and not of a "normal" creation because the existing creation should not be permeated by the fact that life can be created by man since his basic claim is that it was indeed created by some intelligent being.

  13. As we have all seen here with our own eyes, the existing creation does not seek the truth. He doesn't even admit the simple fact written in black and white on the website that he was wrong big time at least 4 times. and serious logical errors.

    In contrast to the normal person, in the creature language is not used for communication, transfer of information and new knowledge. For him, language serves as a strong wall in front of the facts. The excuses will never let the facts sink in.

  14. Someone from somewhere:
    Just search for yourself about each and every one of them.
    I have already shown you that regarding cytosine which you claimed they failed to produce - they already did it in 1903, so now - instead of canceling and making unfounded claims and sending me to work for you - do for yourself with regard to all the amino acids and nucleotides (except cytosine) what I have already done for you regarding cytosine.

  15. Michael, where did you see that they were able to create all the amino acids and nucleotides? The following will correspond to your words. I think you are wrong.

  16. Someone from somewhere:
    It is indeed necessary to create all the nucleotides to create artificial life.
    What I said again and again is that they did produce *all* the nucleotides and *all* the amino acids artificially and did so many years ago.
    You claimed that they did not and your claim is simply factually incorrect.
    To prove that they didn't do it, you gave an example of a case where they tried to do it in a certain way, but you ignored the fact that they actually did it in another way.

  17. To Michael - I didn't understand what you were talking about. I said in the interpretation that you have to create *all* the nucleotides and *all* the amino acids in order to create artificial life, that's all. So how does science announce that in a few years they will create artificial life? I have no idea...

  18. Someone from somewhere:
    But this is completely different from the claim you made at the beginning of your words.
    It's like telling me that a certain nucleotide cannot be made because someone tried to make the nucleotides with a hammer and nail and failed.
    You didn't talk about this or that experiment, but you claimed that they failed to produce cytosine.
    This is a lie because already in 1903 cytosine was produced.
    They didn't do it with hammer and nails or in the Yuri Miller experiment, but they did it anyway.
    What is difficult for you to understand here?

  19. to Michael-

    Quote-"In Miller-Urey-type experiments in which they tried to produce organic substances under laboratory conditions, no nucleotides were formed. These are supposed to have been formed from a combination of a nitrogenous base, ribose, and phosphorus, which probably existed in the ancient world" - do you have a source Did you change your word?

    Also refer here-

    http://he.wikipedia.org/wiki/%D7%A0%D7%99%D7%A1%D7%95%D7%99_%D7%99%D7%95%D7%A8%D7%99-%D7%9E%D7%99%D7%9C%D7%A8

    Quote-" 2% of the carbon content in the experiment turned into amino acids - 3 out of the 20 amino acids that appear in living things. The amino acid that formed in the greatest amount was glycine.

    Conclusion - not all nucleotides and not all amino acids were formed.

  20. Someone from somewhere:
    The link you provided also does not say what you claimed it said.
    The only sentence in which the word "cytosine" appears in this link is the following sentence:
    "One of the nucleotides, cytosine is easily degraded and scientists have not yet been able to define a reasonable simulation for its activity in the prebiotic world."
    The distance between this claim and your claim that "the very fact that no scientist was able to create all the bases and also the amino acids is a problem" and the claim "Yes. No scientist created all the nucleotides. They were taken from living cells in this experiment." It is very big and as mentioned these two claims of yours are simply false.

  21. A little order is made:

    The Hebrew Wikipedia relies in this case on an article by Levy and Miller from 1998, which tries to decipher whether the first life was created at high or low temperatures. According to the article, tyrosine has a half-life of 19 days at a temperature of 100 degrees Celsius. This fact requires that the first life was formed in less than a hundred years, assuming that the temperatures did reach such a level at the time of the beginning of life.
    Another possibility is that the temperatures will be lower. At zero degrees Celsius, tyrosine reaches a half-life of 17,000 years, which gives a period of the order of a million years, during which the first life could have formed.

    In short, the relatively short half-life of tyrosine does not contradict the RNA world theory.

  22. I just have to say "ummmm"...
    It's a shame that there is no website blocking software for creationists, although thanks to this useless debate I actually found a benefit and learned from people's answers to the baseless claims. I just had to remember to ignore a certain someone…ummmm….

  23. Someone from somewhere:
    That's not what they say.
    They say they will make everything synthetically.
    Maybe you can finally show me on Wikipedia the link on which you base your claim?

  24. Yes. No scientist made all the nucleotides. They were taken from living cells in this experiment.

  25. Ummm, looking at the wiki it turns out that there is a problem with the nucleotide cytosine. And the very fact that no scientist has been able to create all the bases as well as the amino acids is a problem. How then can scientists claim synthetic life? Why haven't they created them all yet?

  26. Note that other nucleotides have also been found in the meteorite, but they are simply not sure whether they are from the Earth or from space. In any case, since scientists were able to find one type of nucleotide in one meteorite with certainty, there is a good probability that others will be found as well, partly because the chemical formula of all of them is similar at its base.

    As for synthetic life, it is possible to create such in the laboratory even without discovering the way in which nucleotides are formed in nature. Already today there are chemical ways in the laboratory, through which it is possible to create all five nucleotides (adenine, guanine, cytosine, thymine and uracil) that exist in nature.

  27. That's exactly what I said - only one of the four nucleotides can be found. What about all the rest that are necessary? That would be a problem. How do the scientists claim that they will produce synthetic life in a few years when they have not yet produced nucleotides?

  28. The fact that something has zero statistical chance of existing does not mean that it did not exist.

  29. The "someone" proved his incompetence in the field he is talking about, and showed that he does not know that urocil is a nucleotide (of RNA, by the way). He is a creationist who is convinced of his position beyond any reasonable doubt, and no evidence will disprove his theory. Therefore, it is better to ignore from him.

  30. In the meteorite they found, among others, xanthine and uracil. Xanthine is a building block of nucleotides, and uracil is an actual nucleotide, and serves as one of the four nucleotides that can be found in RNA.

    As for the pollution, the latest research has actually shown that there is good certainty that these molecules are of space origin, and not from terrestrial pollution.

  31. Sorry Roy, but it is not listed where the nucleotides were found. Only the building blocks of the nucleotides and that is also not certain because of a supposedly contaminated source. So far I have heard that they managed to create only one of the four nucleotides in some experiment.

  32. Another point that Roy raised is that complementary templates are required here, which lowers the likelihood even more (I won't go into detail now). Therefore, as Roy said, we need a replicator of individual nucleotides, one by one. Does anyone even know of such a replicator?

    And for the time being, only an intelligent factor assembled an RNA molecule and another that was taken from living cells. So experience actually shows the opposite. Nucleotides have never been found in any natural environment. Even in an experiment, it seems to me that only one was created.

  33. Be serious. No one seriously claims that they ever assembled molecules and randomly assembled complete RNA. Also no one knows if the RNA was in the opening stages.

    But what is certain did not happen: a disappearing hand came down to earth and started assembling RNA molecules.

  34. someone,

    First of all, RNA polymerase is a sophisticated protein enzyme, and is not related to the topic.

    Second, the current RNA enzyme consists of four oligomeric subunits of RNA - each of them is a few dozen nucleotides long, or maybe less (I don't have access to the full article, but oligomer means 'a few units' - between three and a few dozen). It is very likely that such oligomeric subunits will be formed randomly in certain areas on the earth, especially in view of a discovery from last month that shows that RNA can spontaneously connect to oligomers under the right conditions.

    Eran,

    The experiment is not supposed to recreate primordial life on Earth, especially since pre-prepared strands of RNA are needed. There is indeed a statistical possibility for the existence of such strands, but this seems to be a very inefficient method of reproduction.
    In order to have a more suitable life form, we would certainly want an RNA enzyme that would be able to attach single nucleotides to itself, one by one.

    good week,

    Roy.

  35. Lami Bachar-

    So this way - if the length of a replicating molecule is only 1000 nucleotides (in reality probably more) then it can be arranged in 1000^4 different configurations. The number of atoms in the universe does not exceed 80^10 which is absolutely nothing. With a quick calculation you will find that it also has all the stars of the universe ( 20^10 or so) were exploded into molecules and in every possible configuration, so after 14 billion years it would not cover more than 80^10 different sequences, and even if we consider synonyms, it is nothing. And the scientists themselves understand this, and therefore they claim that there may have been shorter molecules. This is also one The main problems in creating artificial life. The scientists are not able to create a proto-cell with less than dozens of different components. And it is also clear why - the creationists will jump at the idea and directly claim (and rightly so) that only planning can create a simple cell.

    "After all, a constant evolution begins which enables an increase in the conditions for survival and a natural selection of the more adapted." - The question is how evolution beyond replication is possible. What advantage is possible for a dangerous molecule beyond replication? In my opinion, it is not possible and this is what happens in the laboratory...

  36. Mr. Somewhere,
    I agree with the spirit of your words but you happen to be careful with the statistical statements.
    Don't forget that the creation of life is not about billions of years in a small test tube. This is a huge area and volume and a considerable amount of time (although on Earth the window of opportunity is up to 4 billion years and not 14, but this does not mean that the origin of life is from the Earth). Therefore, one should refer to areas and volumes on the order of the size of the universe and the times you mentioned, assuming they are correct, and then try and refer to statistics - if necessary (I find the whole thing marginal).

    As soon as life is created for the first time (and even in several foci at the same time or at different times) then a constant evolution begins which enables an increase in the survival conditions and a natural selection of the more adapted ones. So the main problem, as we will see, is really the first spark.

    Greetings friends,
    Ami Bachar

  37. A serious problem in the experiment-

    "The subunits in the enzymes assembled by the group contain many nucleotides, each of them, so they are relatively complicated. It is hard to assume that they could have been found floating in the ancient soup." - Obviously, it is hard to believe. RNA polymerase is made up of thousands of nucleotides and I assume that the above molecule is also made up like that. The chances of its formation by chance are probably zero, even in a window of opportunity of 14 billion years or more Depends on how big it is.

    "But even though the original building blocks were probably simpler, "- it's a fact that they weren't. See above

    "This work finally shows that a life form based on RNA is indeed possible." - maybe technically possible but not statistically.

    Another problem is what is beyond that? After all, a molecule replicates and replicates and what's next? This is probably what they will test next time. It will be interesting to see what comes out, if at all...

  38. It is really interesting and indeed we will see when the second phase of the beginning of life returns

  39. I didn't understand, why can't the results of this experiment be regarded as a return of the beginning of life on Earth? Isn't that how life began to develop? Wasn't that the starting point?

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