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Published online 8 January 2009 | Nature | doi:10.1038/news.2009.5

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A never-ending dance of RNA

The recreation of life's origins comes a self-catalysing step closer.

Erika Check Hayden

RNA, a chemical related to DNA, can be used as the basis of a system in which pairs of molecules endlessly reproduce each other. The system allows molecules to evolve in ways that could throw light on the origins of life.

The RNA in ribosomes may be a relic of an "RNA world"DR TIM EVANS / SCIENCE PHOTO LIBRARY

The work furthers the fortunes of the 'RNA world' hypothesis1. This body of thought suggests that early in the evolution of life RNA was used both to store genetic information (a role now taken by DNA) and catalyse chemical reactions (something now mostly left to proteins). Andy Ellington of the University of Texas at Austin predicts that the paper will be seen as "a watershed event" for people thinking about early life: "This is going to have a huge impact with respect to the RNA world."

But the authors of the paper caution that their work does not prove that life on earth evolved this way. "This is a system that embodies self-replication, mutability and heritability — we're not trying to put too fine a historical point on it," says Gerald Joyce at the Scripps Research Institute in La Jolla, California, a champion of the RNA world hypothesis and one of the researchers who carried out the work, published online in Science2.

Immortal activity

Joyce and his colleague Tracey Lincoln made paired RNA catalysts, each of which could assemble the other when supplied with the right building blocks. Then the scientists mixed the paired molecules with RNA building blocks in test tubes. Because the RNA 'enzymes' were not perfect, and made different forms of each other, the original pairs mutated into new, 'recombinant' forms that out-competed the originals. The 'winning' enzymes changed depending on the conditions in the reaction mixture, such as the concentration of various RNA building blocks.

“This is proof that an RNA self-replicating system is possible”

David Penney 
Massey University

Joyce's group had already made enzymes capable of catalyzing their own replication, but they could only reproduce themselves a limited number of times. The new enzymes can reproduce themselves indefinitely. "This is the first time outside of biology where you have immortalized molecular information," says Joyce.

David Penny, a theoretical biologist at Massey University in Palmerston North, New Zealand, says the work fulfils a prediction made decades ago by Nobel laureate Manfred Eigen and biophysicist Peter Schuster. In the 1970s, the pair proposed that 'hypercycles' — networks of enzymes that replicate each other — could give rise to self-sustaining populations of early life forms3.

"This is proof of principle that an RNA self-replicating system is possible," says Penny.

Evolving solutions

Ellington says that the observation that different winning enzymes emerge in different conditions is crucial because it further undermines the intelligent-design idea that life is too complex to have arisen without the intervention of a supernatural being.

“The goal here is to make life in the lab. Ultimately, that's where we want to go”

Gerald Joyce 
Scripps Research Institute

"This paper shows that Darwinian evolution wins out," he said. "Joyce is emphatically knocking down a straw horse of the intelligent-design community."

But the system is a long way from being the origin of life recapitulated in a test tube. Eric Smith, a researcher in the field at the Santa Fe Institute in New Mexico, agrees that the work is elegant and important. But he points out that Joyce's enzymes have benefited from years of study and tinkering in the lab, and are being asked to perform relatively simple operations. "What we can do in the lab is such a tiny fraction of what we would need to do to make strong arguments about the origin of life that there is huge room for imagination and presumptions to influence research directions, right or wrong," he says.

Other prominent scientists, such as Craig Venter of the J. Craig Venter Research Institute in Rockville, Maryland, and Jack Szostak, of the Howard Hughes Medical Institute in Chevy Chase, Maryland, are also trying to create life in the lab. But while Venter is using a top–down approach — trying to 'boot up' a cell with an entirely synthesized genome — Joyce and Szostak take a bottom–up strategy by attempting to recreate the events that could have led to the existence of genes, cells and life as it is now.

Joyce says the next major step would be to create a system that doesn't just do the same thing over and over, but can evolve the ability to perform new tasks. "The goal here is to make life in the lab, and we have not achieved that, because the system does not within itself have the ability to present novel functions. But ultimately, that's where we want to go,"  he says.

  • References

    1. Gilbert, W. Nature 319, 618 (1986). | Article | ISI |
    2. Lincoln, T. A. & Joyce, G. F. Science 10.1126/science.1167856 2009 (2008).
    3. Eigen, M. & Schuster, P. The Hypercycle: A Principle of Natural Self-Organization (Springer, 1979).  


Comments

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  • This most certainly helps to demonstrate that the RNA world did at one time exist, and RNA self-catalysis certainly is a feature that supports RNA as capable of hosting a genetic code directly. However, I have reason to believe that the earliest life forms were systems of protiens in which RNA had only a minor if any role. My reason is based on my experiences as a software engineer. Every time I see a system that is of a form of A -> B -> C and which evolved into that form over time, C inevitably is the oldest and most basic form, and A is the most recent and also the most powerful. An example is the early pattern of HLL (higher level language such as FORTRAN or COBOL) -> Assembly language -> machine language. Now look at the how genetic information flows: DNA -> RNA -> protiens. That tells me right off of the bat the protiens were the initial thing that life was made of. RNA was coopted into the process later, providing a standard way of creating various protiens and controling their rate of creation. Still later DNA provided and even more robust way of generating the RNAs and providing even greater control. All of this may have happenned early in the history of life, but the signature is still there.

    • 08 Jan, 2009
    • Posted by: Edward Schaefer
  • "it further undermines the intelligent-design idea that life is too complex to have arisen without the intervention of a supernatural being. " Boy that's a jump. This RNA molecule was a "designed" molecule. For the "RNA World" hypothesis to be possible, one has to show that such a molecule could form on its own. This is no minor detail, as the "RNA building blocks" are quite instable. Furthermore, this designed RNA molecule, R3C, simply "stiches" together two halves of itself. I believe Joyce inundated the environment with halves of the same molecule. Kind of stacked, don't you think? It seems to be kind of circular reasoning, we have a replicating RNA... that we built. It stitches together two RNA strands to make another replicating RNA. How did that first one come about? Ummm... Another replicating RNA stitched together two smaller sequences? I'll be interested to read the actual article when it comes out. Specifically, the length of this RNA molecule. Another link that gives a bit more is at New Scientist.

    • 08 Jan, 2009
    • Posted by: Anthony Tyler
  • The beauty of these experiments is that they demonstrate the evolution of complex replicating molecules from starter molecules which would possibly no longer survive in later evolved mixes. Darwin's "bottom up" hypothesis of simple systems evolving into more complex systems is demonstrated successfully and opens the door for testing the possibilities of "proteins first" or "proteins & RNA" co evolving. It would be exciting if we could observe different lineages of molecules evolving. Once we can get the "starter soup" right, many possible futures could evolve from the the same origins.

    • 09 Jan, 2009
    • Posted by: Ian Stones
  • I don't believe in God or gods, but I do delight in the smugness of Scientists who think they have an inside track on what IS or IS NOT so; Am I the only one who sees the irony of an intelligent being, stating that its express goal is to create life in the lab while apparently trying to rule out that any other being might have done so in the past? : ?The goal here is to make life in the lab. Ultimately, that's where we want to go? Gerald Joyce Scripps Research Institute ------------------------------------------------------------- THIS is the most crucial aspect of this research, not simply trying to further science?: "Ellington says that the observation that different winning enzymes emerge in different conditions is crucial because it further undermines the intelligent-design idea that life is too complex to have arisen without the intervention of a supernatural being."

    • 10 Jan, 2009
    • Posted by: Alexander Hoffs
  • ?Excited? or ?exhilarated? would be more appropriate than ?smugness?. Science can never prove a negative or ?rule out? any possibility, including that our carbon based, protein and nucleic acid based replicators were seeded by an intelligent being. These experiments are exciting because in just 25 years we have demonstrated that replicating molecules can evolve from components in probable chemical soups that exist in natural chemical environments and the probability of molecular evolution of competitive replicators is in fact high. It doesn?t rule out several possible origins of replicators that could evolve into very different kinds of intelligent beings, including those, like us that could eventually put chemical seeds on other planets. Intelligent design proponents, if they take the time to study the science done by others, or better still, to try to do the science themselves, will find it harder to demonstrate that complexity cannot evolve from simplicity. Scientists can never be ?smug?, when we know ID proponents seek to squeeze their creator into the ever narrowing gaps and claim we can?t prove the un-provable, that they can?t either. Hopefully in future, we won?t need to think about what ?I.D? proponents say and focus on the exciting adjacent possibilities of scientific exploration that open up with each new discovery. That?s not ?smug?.

    • 10 Jan, 2009
    • Posted by: Ian Stones
  • I don't believe in god or gods, but I do despair at the ignorance of creationists who think they have the inside track on what IS or IS NOT. Put aside the holy trinity (for example) and try and better understand DNA, RNA & Protein. -¬ ALSO: It would also be dangerous to assume that the genetic flow of information is strictly or simply A->B->C. IMO proteins would not have been the initial replicative machinery of the perpetual chemical reaction of life & it was more likely some kind of sugar chain that formed structures. I guess my point is no matter what we believe we may never know for sure. Through science we can come closer to understanding (well certainly in this life).

    • 13 Jan, 2009
    • Posted by: A M
  • It is getting again to the question of what preceded what, the egg or the hen. One could argue that the first step towards life was the spontaneously formed DNA from the soup containing among other numerous organic compounds deoxyribonucleic-acids that more easily could duplicate by organizing into stable double helix, while others have the same strength of argument saying that the weak dissociation of the ribonucleic-acid based RNA macromolecules that were formed spontaneously could be the basis for easier dissociation and replications that could lead to the creation of coded life. Currently both systems have been shown to exist, so it is still hard to determine which preceded the other. In the same sense one could suggest that spontaneously formed proteins from the high temperature organic soup of the young earth could organize into non-specific RNA or DNA polymerases that initiated the formation of RNA and DNA molecules in vast quantity. Part of these nucleic acid polymers could be organized into "sense" RNA and DNA molecules. Those could duplicate and eventually form proteins involved in early ribosome formation which, as more specific composite machinery could accelerate this cascade of early life formation.

    • 13 Jan, 2009
    • Posted by: rafi gorodetsky
  • To A.M - I hear you, but I find it hard to discredit a pattern that I see arising spontaneously over and over again. However, I cannot totally poo-poo your belief that sugars were involved in the earliest forms of life. Even so, to me life is composed of self-perpetuating and reproducting chemical SYSTEMS: No one molecule is behind it. Yes, the first life must have been fairly simple and sloppy, but it still must have been a system that brought in resources and as needed expelled waste. IMO it almost certainly lacked celluar structure and anything like the modern genetic code, but it still met the basic definition given above. --- As for Creationists: That is always going to be a hard nut to crack. One devout Christian that I know made it clear to me that he refused to endorse evolution because that would mean that "the Bible is a lie". Indeed, this need to validate the holy scriptures is very much at the heart of this business. I for one see the Bible as an amazing source of wisdom, morality, history and lore. However, a scientific textbook it is not, and given that it was written by and for people who lived thousands of years ago it never was and never could have been. Even as the devine work of God, He would have known better than the try to describe our modern scientific findings to a group of people who spent most of their time ensuring that they would have enough to eat and drink in the days and months ahead.

    • 14 Jan, 2009
    • Posted by: Edward Schaefer
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