Pharyngula

Chemical replicators

i-e88a953e59c2ce6c5e2ac4568c7f0c36-rb.png

We’re one step closer to self-sustaining chemical replicators, similar to what would have existed a few billion years ago, before true cells evolved. Lincoln and Joyce have created a couple of relatively simple molecules that assemble themselves from even simpler precursors in a test tube.

It’s not as straightforward as the simplest scheme one might imagine. The simplest model would be for a single enzyme, E, to catalyze its own assembly from two smaller precursors, A and B. This formula would lead to a test tube full of A and B to be quickly converted to a test tube full of nearly nothing but E with the introduction of a single copy of E. The actual solution is a little more difficult to explain.

In this case, enzyme E is built from precursors A’ and B’. Enzyme E does not catalyze its own construction, but that of enzyme E’, which is built from precursors A and B. So E catalyzes A + B → E’, and E’ catalyzes A’ + B’ → E. Got that? It ends up with the same result — E and E’ together quickly gobble up all the A, B, A’, and B’ in a test tube, producing a mixture of mostly E and E’. It’s diagramed here:

i-ef96ba1705ab49fcc9d2e13ace201ecc-rna_rxn.gif
(click for larger image)

The enzyme E´
(gray) catalyzes ligation of substrates A and B (black) to form the enzyme E, while E catalyzes ligation of A´ and B´ to form
E´. The two enzymes dissociate to provide copies that can
catalyze another reaction.

Those of you who are already familiar with Stuart Kauffman’s work will recognize this as an autocatalytic set, exactly the kind of thing he predicted would be an early chemical precursor to life. It’s also the simplest kind of autocatalytic set, with only a pair of elements working together; there’s nothing to say there couldn’t be three interlocking cycles, or four, or a hundred, instead of just two. It’s darned cool.

Now you might be saying, “But these are designed enzymes, created by a couple of intelligent scientists!” Not quite. They started with a very rough sequence, one that inefficiently catalyzed an A + B → E sort of reaction, but that not only worked slowly, but also produced faulty products that eventually killed the reaction after a few cycles. Then they tweaked it to form a minus-strand enzyme, and then they subjected both the plus and minus strand forms to — natural selection! They made copies with mutagenic PCR (so they had a range of random variants), ran it through several cycles of in vitro selection for more efficient forms, and ended up with two RNA enzymes that were good at building copies of each other.

Here are the actual RNA sequences of the two enzymes.

i-c7f0406b30fc6bad6384fd974de9b6fb-rna_seq.gif
Sequence and secondary
structure of the complex formed between the enzyme and its
two substrates (E´, A, and B are shown; E, A´, and B´ are the
reciprocal). Curved arrow indicates the site of ligation. Solid
boxes indicate critical wobble pairs that provide enhanced
catalytic activity. Dashed boxes indicate paired regions and
catalytic nucleotides that were altered to construct various
cross replicators.

I can imagine the next objection: those are fairly long strings of nucleotides, and the precursors are fairly complex oligonucleotides, too. The point, however, is that it is a more complex enzyme built up from simpler precursors. No one is pretending this is an example of the earliest chemical reactions — it’s more like a proof of concept of the idea.

Another cool thing about this experiment is that the enzymes proved to be efficient and robust. Below, you can see that they acheived exponential growth, only leveling out when the substrates were exhausted.

i-a320bd953db5ba114e62b471c2d1c4b5-rna_exp.gif
Ultimately the system should provide open-ended
opportunities for discovering novel function, something that
Self-sustained amplification of cross-replicating RNA
enzymes. (A) The yield of both E (black) and E´ (gray)
increased exponentially before leveling off as the supply of
substrates became exhausted.

These enzymes worked well. If they were producing deleterious byproducts that were interfering with the reaction, you’d expect to see a gradual decline in the rate that was independent of the reduction in concentration of the substrates; no such effect was observed in the experiment below, where substrates were regularly replenished. These paired chemical replicators were just cruising, reliably making lots of copies of themselves, and they could keep going for ages…like, 4 billion years.

i-7bd726fb1a1d7c901f89c17954d5c52e-rna_rep.gif
Amplification was
sustained by performing a serial transfer experiment, allowing
~25-fold amplification before transferring 1/25th of the
mixture to a new reaction vessel that contained a fresh supply
of substrates. The concentrations of E and E´ were measured
at the end of each incubation.

Again, don’t have illusions that this is an example of a resurrected chemical function from the dawn of time — it’s a demonstration of the feasibility of one part of the process of chemical evolution. The authors also mention another interesting feature of the work in their conclusion.

Ultimately the system should provide open-ended
opportunities for discovering novel function, something that
likely has not occurred on Earth since the time of the RNA
world
, but presents an increasingly tangible research
opportunity. enzymes.

People often wonder why these kinds of prebiotic reactions aren’t going on all the time in the world around us, and the authors agree that this is not something that can occur naturally right now. Why? The answer is simple: the world around us is swarming with the ravenous, finely-honed products of billions of years of evolution, creatures like bacteria, that would readily swoop down on any accumulation of nucleotides and consume them before these kinds of reactions could even start. Nowadays, it takes a sterile lab and many precautions to put these chemicals into the kind of coddled environment where they can evolve.


Lincoln TA, Joyce GF (2009) Self-sustained replication of an RNA enzyme. Science Jan 8. [Epub ahead of print].

Comments

  1. #1 gene
    January 11, 2009

    Cool, I can’t wait until we make kinematic self replicating machines.

  2. #2 Kel
    January 11, 2009

    Very cool stuff.

  3. #3 The Science Pundit
    January 11, 2009

    Once again, it’s shown that natural selection could be an integral part of one aspect of abiogenesis, putting the lie to “Evolution has nothing to do with the origin of life.” I hate it when I hear people (on my side of the evolution vs. creationism debate) say that.

    I also find it interesting that just about every proposed mechanism for abiogenesis either still exists today (if you look hard enough), or can be easily duplicated by moving to a sterile environment (like this experiment).

  4. #4 Glen Davidson
    January 11, 2009

    But this will never be good enough, when compared with a god who could and would do anything (including make P. falciparum, complete with evolutionary history).

    And of course this is why nothing ever convinces them, because the difficulties of science are nothing compared to a god who is already assumed. The mere fact that there is no evidence for this god matters not to them.

    Beyond that, I’d say that there are questions about the stability and concentrations of RNA. Some think one of the nucleotides has to be replaced for the sake of stability, and of course there have been regions/times where/when RNA was increased in density, so it’s a good try.

    But it will never compare with an unevidenced, thus unlimited god, no matter what is discovered.

    Glen D
    http://tinyurl.com/6mb592

  5. #5 dc-agape
    January 11, 2009

    I never doubted that it would work! But then I’m a chemist! Thanks Doc, for the info. I have been waiting for this, but knew that the sterile field would be one factors needed. Cool!

  6. #6 The Heat
    January 11, 2009

    Just a little nitpicking about the exegesis. I was a little confused at first. The prime notation led me to expect that A’ and B’ were going to be variants or minor modifications of A and B. Why not just say that A and B yield E and A’, B’ yield E’? Or introduce new symbols, C and D? Still, it’s a pretty good summary. I can follow Meyer’s description of the process much better than I can follow the diagram, which sets my head spinning.

    About the selection process: I think I see why it’s innaccurate to call these designed molecules. But they aren’t naturally selected, right? Wouldn’t Darwin call this a process of artificial selection? I take it that the selective pressures are entirely posed by the researchers. They picked the “fit” molecules, right? Is there some sort of corresponding scenario in which natural selective pressures would give the same result?

    Nonetheless, this is a nifty, suggestive experiment.

  7. #7 techskeptic
    January 11, 2009

    I hate it when I hear people (on my side of the evolution vs. creationism debate) say that.

    LOL, i’m pretty sure I have seen PZ say that!

    Quick question: I understand that A & B and not meant to represent a particular reagent in the primordial soup. But presumably this is showing a chemical process that that happened way back when. so my question is, what was making A & B or its counterparts? At some point something had to start replicating, but before that nothing as replicating, so what was making the initial consumables?

    Or is this experiment so far removed from what we think actually happened back then that the question is irrelevant?

  8. #8 AnthonyK
    January 11, 2009

    But doesn’t this contradict the Law of Getting Something I Don’t Understand From Someting I Think I do?
    I mean, I can grasp A and B – but E? Has anyone ever seen E appear all on its own? Of course not!
    One in the eye for you, scienceboy!

  9. #9 Last Hussar
    January 11, 2009

    Can some one just confirm something for an Amature Physics freak- I sometimes feel out of place amoung all these bio freaks-

    A and B are inorganic- or at least could be. Also though as PZ said there was some ID to start, this could happen without outside help- it’s just that the researchers couldn’t sit around waiting for the 99.999% of times these 2 met and nothing happened, unlike the millions of years Life had.

    Thanks

  10. #10 Jadehawk
    January 11, 2009

    so let’s see if i got this right..

    when separated, A + B –> E’ and A’ + B’ –> E is possible, but slow and stops eventually. but when A, A’, B, B’ are put together, then only the first set of E and E’ develops in the slow way, while after that first pair the reactions are mutually reinforcing and the reaction takes off like crazy.

    is that right, or am i confused?

  11. #11 John Marley
    January 11, 2009

    techskeptic: (#7):

    from the post:

    No one is pretending this is an example of the earliest chemical reactions ? it’s more like a proof of concept of the idea.

  12. #12 Aquaria
    January 11, 2009

    PZ, this is a reason I was in so much withdrawal from the site that I went so low as to read about 18th century tarts (the naughty kind). It was fun and informative (grad school historians FTW!!11!!), but I’ve been waiting for you to address this very cool story.

    Since I have nothing to contribute, though, I’ll sit back and watch everyone discuss it. If it’s okay to ask a question from the dunderhead gallery when one occurs to me?

  13. #13 DLC
    January 11, 2009

    Cool. proof of concept.
    I’d like to see it replicated a few times, though. :-)

  14. #14 Sigmund
    January 11, 2009

    A and B we can understand.
    The big problem for you evilutionists is to get to E what do you need?
    C and D!
    Two missing links!

  15. #15 Nerd of Redhead
    January 11, 2009

    Another little step in abiogenesis crossed off. Still a long ways to go, and it will never be appreciated by creobots, who simply can’t understand deep time.

  16. #16 Justin
    January 11, 2009

    In the third paragraph when PZ says “Got it?” I don’t think I really do, can anyone help on that? The rest makes sense but I’m not quite getting that part. I may be stupid but what is the difference between E (Enzyme) and when the E has an apostrophe next to it? the E’

    @AnthonyK

    Back in my younger days E appeared in my my drink at a rave, seemingly on it’s own.

  17. #17 Susan
    January 11, 2009

    Now you might be saying, “But these are designed enzymes, created by a couple of intelligent scientists!”

    They are, too! REALLY intelligent. I’m related to one of them, and I’ll be unbelievably excited if one of my relatives ends up proving that the gods are irrelevant.

    You can hear him talk about this on NPR, too.

  18. #18 Timebender13
    January 11, 2009

    I’m surprised I understood that…..

    Anyway, more evidence for evolution! Creationists want to know how life started? Well here you go! No god needed, just simple enzymes!

  19. #19 tsig
    January 11, 2009

    The enzymes were still enzymes so no macroevolution here.lol

    Next thing you know you’ll be trying to tell us that we are just chemicals.

  20. #20 Romeo Vitelli
    January 11, 2009

    This raises an interesting conundrum:
    If biologists succeed in creating life, that makes them the equivalent of gods.
    If they also happen to be atheists, does that mean they have to stop believing in themselves?

  21. #21 arvind
    January 11, 2009

    Breaking news! Hot off the press! Abiogenesis gap filled! Extra! Extra! God forced to move back 11 billion years! God says he’s fucking tired of moving! Read all about it! God damns “those fucking meddlesome scientists” to hell! God says they haven’t heard the last of him yet!

  22. #22 Rebecca C.
    January 11, 2009

    Ultimately the system should provide open-ended opportunities for discovering novel function.

    Give those puppies a swimming pool full of substrate and let ‘em run. Let’s see what happens! I for one welcome our ant overlords.

  23. #23 PZ Myers
    January 11, 2009

    The terminology is straight from the paper: see the first and second diagrams for illustrations.

    E and E’ differ in the sense of the RNA strands, one having the same sequence in the 3′→5′ direction as the other has in the 5′→3′ direction.

    Jadehawk has it right.

  24. #24 Donnie B.
    January 11, 2009

    Justin, as I understand it, E is one particular enzyme, and E’ is a different enzyme.

    Similarly, A and B are simpler molecules that can link up to form E, and A’ and B’ are different simpler molecules that can hook up to form E’.

    The cool thing is, the presence of E’ catalyzes the A + B -> E reaction; and the presence of E does the same for the A’ + B’ -> E’ reaction.

  25. #25 Susan
    January 11, 2009

    The cool thing is, the presence of E’ catalyzes the A + B -> E reaction; and the presence of E does the same for the A’ + B’ -> E’ reaction.

    Joyce described it as being similar to that Escher litho with two hands drawing each other. That’s when I understood it. (But I’m a bureaucrat.)

  26. #26 Donnie B.
    January 11, 2009

    Susan, that’s a really nifty analogy! Kudos to Joyce for that.

  27. #27 dreikin
    January 11, 2009

    The Heat (#6):
    Really, the only difference between natural selection and artificial selection is whether humans were intentionally influencing it. Aside from that though, from PZ’s post (I haven’t read the actual paper yet), it looks as though it’s pretty close to what would be the ‘natural’ form of selection – which ones where ‘chosen’ were simply those with the most children. The only thing (maybe) missing was the presence of other chemicals that might produce adverse reactions.

    techskeptic (#7):
    Both. If something like this happened, it’s step number was prolly in the hundreds, if not higher (step 1, step 2, … step {this}, etc.). But the process could probably be extended backward for a fair bit as well – just make similar, but smaller, versions of the same thing. Trim some of the excess (use shorter, mutated versions of A/A’ and B/B’). You’ll reach a point where this doesn’t work anymore – but some other process might. Can also grow by the same mechanism, but extending rather than trimming.
    If recursion means anything to you, it’s similar.

    Romeo Vitelli (#20):
    How about becoming auto-deists?

    Susan (#25):
    Awesome analogy find!

  28. #28 Eamon Knight
    January 11, 2009

    Once again, it’s shown that natural selection could be an integral part of one aspect of abiogenesis, putting the lie to “Evolution has nothing to do with the origin of life.” I hate it when I hear people (on my side of the evolution vs. creationism debate) say that.

    I hear you, but first understand the creationist argument that precedes it: they think that by picking on the least certain aspect of natural history they are somehow casting doubt on the whole thing (especially the connection of humans to apes, ie. the thing that really makes them squirm). As a practical matter, it is worth trying to subdivide the debate into distinct areas — abiogenesis; evolution of organismic life; fossil record; human ancestry; etc. I agree there should be better ways of expressing it.

  29. #29 Justin
    January 11, 2009

    Cool that clears it up, thank you for taking the time to educate the film major.

  30. #30 The Science Pundit
    January 11, 2009

    Eamon Knight @#28:
    You’re right. I’m familiar with the creationist argument that precedes it, so I understand the sentiment. Maybe I’m just too much of a perfectionist. And let me assure you that I don’t wince nearly as much when people on my side say “Evolution has nothing to do with the Big Bang!” ;-)

    Susan @#25:
    I really like that analogy!

  31. #31 Eamon Knight
    January 11, 2009

    Once again, it’s shown that natural selection could be an integral part of one aspect of abiogenesis, putting the lie to “Evolution has nothing to do with the origin of life.” I hate it when I hear people (on my side of the evolution vs. creationism debate) say that.

    I hear you, but let’s first understand the creationist argument that usually precedes it: they think that by picking on the least certain aspect of natural history they are somehow casting doubt on the whole thing (especially the connection of humans to apes, ie. the thing that really makes them squirm). As a practical matter, it is worth trying to subdivide the debate into distinct areas — abiogenesis; evolution of organismic life; fossil record; human ancestry; etc. I agree there should be better ways of expressing it.

  32. #32 Gregory Kusnick
    January 11, 2009

    dreikin (#27):

    Really, the only difference between natural selection and artificial selection is whether humans were intentionally influencing it.

    I think the mode of influence has a lot to do with it. The usual sense of artificial selection (as in animal or crop breeding) involves human intervention in every generation. Breeders choose which specific individuals to cross to promote the traits they want.

    That didn’t happen here (and couldn’t in any practical sense). The experimenters simply set up a fitness landscape and let evolution find its own way through that landscape. That makes it natural selection in my book.

  33. #33 Kel
    January 11, 2009

    In that sense, is sexual selection a form of artificial selection when done by humans?

  34. #34 Gregory Kusnick
    January 11, 2009

    In that sense, is sexual selection a form of artificial selection when done by humans?

    I’d say no. (There’s no conscious plan spanning generations.) But arranged marriages might be.

  35. #35 Cubist
    January 11, 2009

    Meteorology doesn’t cover where Earth’s atmosphere came from in the first place.
    Orbital mechanics doesn’t cover how the planets originally formed.
    Why should anybody think that evolution includes how life originally formed?

  36. #36 hje
    January 11, 2009

    Then they tried to enhance their capabilities, by letting them work together…

  37. #37 Katkinkate
    January 11, 2009

    Cubist, many of them think the theory of evolution is about how everything came into existance, from the big bang to now. All under the control of the great god Darwin.

  38. #38 PeteC
    January 12, 2009

    People often wonder why these kinds of prebiotic reactions aren’t going on all the time in the world around us…..

    PZ’s following explanation is exactly right, but of course (as PZ knows) the credit for originating the counterargument goes to Charles Darwin in a letter to Joseph Hooker:

    It is often said that all the conditions for the first production of a living organism are present, which could ever have been present. But if (and Oh! what a big if!) we could conceive in some warm little pond, with all sorts of ammonia and phosphoric salts, light, heat, electricity, etc., present, that a protein compound was chemically formed ready to undergo still more complex changes, at the present day such matter would be instantly devoured or absorbed, which would not have been the case before living creatures were formed. (Emphasis mine)

    What a big if.. so many researchers are creating enough warm ponds these days that we may eventually regard abiogenesis as trivial. Not that we will understand in detail how it really happened on earth, but we may someday be able to regard the problem with nonchalance. “Of course replicators emerged on earth, how could they not?”…

  39. #39 amphiox
    January 12, 2009

    On the “evolution has nothing to do with the origin of life” argument:

    I think the accurate thing to say that evolutionary theory does not attempt to explain the origin of life, and is not dependent on any particular mechanism for the origin of life. Once a lifeform arises, it will begin to evolve. Humans might intelligently design a lifeform in a lab somewhere, someday, but that lifeform would start evolving the moment we took our eyes off it (probably even before).

    Whether or not evolutionary mechanisms were involved in the origin if life is another question entirely, and depends at least partly on exactly how you define “life.” Because if, for example, you define life as any chemical self-replicator, then, by definition, the moment you get replication, you have life, and since evolutionary mechanisms all require self-replication, then by definition, evolutionary mechanisms cannot be involved in the origin of life.

    If, on the other hand, you define life as something more complicated that just a chemical replicator, then, clearly, there is much room for evolutionary mechanisms to have a hand in its origin.

  40. #40 amphiox
    January 12, 2009

    There have been a number of historical examples that I think would qualify as artificial selection of humans. Ancient Sparta being the most obvious example that comes to mind. And more than likely every society with a slavery institution up to and including pre-civil war America.

    Probably from the very moment humans started animal husbandry, at least some of the powerful were trying to do apply the same principles to less powerful people under their control.

  41. #41 amphiox
    January 12, 2009

    I’m sure it hasn’t escaped notice that since E and E’ are reciprocal, they can join up into a single double-stranded molecule.

    So we could conceptualize this experiment as one enzyme, E-E’, catalyzing its own assembly from four precursors, A, B, A’ and B’, with the first step in the process being the separation of E and E’ from each other.

    Which in my mind isn’t actually any different from the example of E catalyzing its own formation from A and B.

  42. #42 Chalmer Wren
    January 12, 2009

    That is really cool!

  43. #43 John Scanlon FCD
    January 12, 2009

    And as ‘God’ was hauled away in handcuffs after being unmasked as an imposter, he said “And I would have gotten away with it too, if it wasn’t for those meddling chemists!”
    /Scooby-Doo

  44. #44 Scott Hatfield, OM
    January 12, 2009

    Once again, it’s shown that natural selection could be an integral part of one aspect of abiogenesis, putting the lie to “Evolution has nothing to do with the origin of life.” I hate it when I hear people (on my side of the evolution vs. creationism debate) say that.

    Ahem!

    Evolution by natural selection as a THEORY obviously has something to do with abiogenesis, as when (in this case) it provides a fertile source of testable ideas about how life might’ve gotten started. Evolution as an empirically-determined FACT about the natural world, however, is still uncoupled from abiogenesis, which at this point amounts to a promising but still speculative research program. Avoiding ontological conflation is not just a nicety, though: it’s important that we not oversell our case to Joe Public, prematurely. It makes the task of promoting science education that much more difficult.

    Peace…SH

  45. #45 Scott Hatfield, OM
    January 12, 2009

    If biologists succeed in creating life, that makes them the equivalent of gods.
    If they also happen to be atheists, does that mean they have to stop believing in themselves?

    I chuckled when I read this. Where’s Bishop Berkeley when you need him?

    Anyway, speaking of metaphysics, there is always the possibility that something like theism could be naturalized. If we can do it (create life), and I believe we will, then others could’ve done it, or can do it now in the right conditions. It’s a big universe, an old universe, and maybe sprung from another realm with its own scale. There could be a whole bunch of beings out there, making life, though of course (from their perspective) atheistically.

  46. #46 Harry
    January 12, 2009

    OK, here goes my first comment on your blog…

    In my opinion, this will probably be one of the most important stories of the year. Who knew that the origin of life would be discovered in 2009 (well, close enough)? Suppose it’s only fair, since the world will be ending soon in 2012 ;).

  47. #47 Peter Ashby
    January 12, 2009

    Well I for one welcome our coddled, artificially selected, self replicating rna overlords!

    And nice quote PeteC, people are often amazed by how much they knew in various areas of science back in Darwin’s day. For eg you can sterilise a water sample by filtering it through certain ceramics with pore sizes that will exclude bacteria. And they had Jenner and Lister etc. So of course the very issue would have arisen in 1850.

  48. #48 KnockGoats
    January 12, 2009

    It’s a big universe, an old universe, and maybe sprung from another realm with its own scale. There could be a whole bunch of beings out there, making life, though of course (from their perspective) atheistically. Scott Hatfield

    This brings to mind a question, or two questions, I’ve long meant to ask an intelligent theist (trouble is, it’s so… no, I’ll resist the temptation).

    1) Suppose I find myself in the presence of an awe-inspiring being, which declares itself to be God, demonstrates it knows my inmost thoughts and complete history, gives me the conviction it is simultaneously loving and judging me, etc. How could I be justified in concluding that this is indeed God, creator and sustainer of the cosmos, Lord of All, etc. etc., rather than just a powerful imposter? (I’m not talking about my subjective conviction here – clearly a sufficiently powerful imposter could bring about this conviction.)
    2) How can God know he really is the CEO, and not just the errand-boy of some super-deity?

  49. #49 Louis
    January 12, 2009

    I suggest people also look into the work of Leslie Orgel and Julius Rebek Jr (to name but two) if they are interested in the work on chemical replicators.

    I dumped a few references here if anyone is interested.

    Apologies for message board post whoring.

    What people might not realise is that there is a huge amount of work that has already been done here, and as I always do, I’ll recommend a book by Pier Luigi Luisi called “The Emergence of Life” and a journal from Springer called “Origins of Life and Evolution of Biospheres”.

    Obviously this stuff requires a certain amount of chemical/biochemical literacy, and hence why it is ignored by almost all creationists, but it really isn’t that difficult to grasp the essence of it (just like the paper PZ is referencing).

    Enjoy!

    Louis

  50. #50 Louis
    January 12, 2009

    What I meant to do above was post the link to here.

    HTML and URL fail: I has it.

    Louis

  51. #51 Louis
    January 12, 2009

    http://www.antievolution.org/cgi-bin/ikonboard/ikonboard.cgi?s=496b1f7653583c3f;act=ST;f=14;t=3902

    LOL I give up. Click/copy and paste the above!

    Double Fail!

    Just FMI how the fuck does one do this HTML url posting malarky? I tried to use [A url = x] and the corresponding [/A] tags (with the proper triangular brackets) and it done summat funneh. Meh, computers were never my thing, too dry and unlikely to explode.

    Louis

  52. #52 John Morales
    January 12, 2009

    Louis, link syntax:
    <a href=”URL”>visible text</a>

  53. #53 Louis
    January 12, 2009

    John,

    Thankyouthankyouthankyou!

    I suppose one of these days I should learn computery things, but I’ve held out for so long it seems to be a shame to change my almost virginal innocence when it comes to computers now. ;-)

    Louis

  54. #54 clinteas
    January 12, 2009

    PZ,
    thanks for pointing out the intricacies of this experiment,It seemed easily refutable by the christozombies by declaring: but,but,the molecules were intelligently designed !

    Not so much anymore,good one !

  55. #55 Amy
    January 12, 2009

    For those of you that are confused about the A,B,E vs. A’,B’,E’, I believe there is a typo. In the text it reads that “E catalyzes A + B ? E’, and E’ catalyzes A’ + B’ ? E” while the figure and the figure legend have E’ catalyzing A + B -> E and and E catalyzing A’ + B’ -> E’. From what I can tell, both E and E’ have the same sense but not the same sequence. They differ by 10 nucleotides in the section where they interact and E’ has a longer hairpin.

    In other news, I seemed to have skipped the philosophical debate in order to point out some overlooked/forgotten details. Why does this not surprise me?

  56. #56 Cannabinaceae
    January 12, 2009

    I second the suggestions of a poster above who commented that selection could be used to work the substrates down to smaller and smaller sizes (eventually hitting a dead end at some size >> 1 nucleotide).

    It would be interesting:

    1. To redo this whole experiment at much higher throughput and see what kind of outliers, if any, selection throws us. Maybe the same starting materials usually evolve to essentially the same endpoint, or maybe not. What are the attractor(s) of the system?

    2. Assuming several different endpoints from 1, (and don’t tell me you didn’t see this coming), put them in competition with each other. What I would hope for out of this is for the system to become more complex, perhaps even throwing in an extra reaction or two.

    3. After getting something out of 2, again select for building up the effectors from smaller and smaller substrates.

    4. Heck, add lipids to see if artificial cells get made if that floats your boat.

    = = = = =

    And: the creationists could put their money where their mouth is*: If they want reasoners to prove a negative (i.e that there are no gods) they should do something similar themselves (that abiogenesis can’t happen); They’re seemingly** so sure that it is impossible to increase complexity or add information, they should fund the above studies for as long as it takes to prove themselves right! If no real life emerges from these experiments after an infinite amount of time***, the rest of us bow down to their twinkle.

    *As if.
    **I say seemingly, because I actually suspect that many of them know they are wrong, but are simply too embarrassed to admit it.
    ***OK, I’ll give them several billion years…

  57. #57 ennui
    January 12, 2009

    I will never bow down to their Twinkie! Maybe a Chocodile. Anyway, lemme see if I’m getting this straight–

    If I take A + B, I get a huge E-reaction.
    Unchecked, this could lead to a mind-blowing organism.
    Right?

    /gluesniff

    Anyone have an idea which abiogenesis niche this is most likely to occur in (e.g. deep ocean vents, sub-surface clays, hydrogenated diamonds, etc.)?

  58. #58 fastpathguru
    January 12, 2009

    I posted a comment about this last Friday…

    See my inappropriately-placed comment #36

    The really coolest thing about this (in the Wired story) is that after 50 or so generations, the replicators had evolved into several strains with a subset of the variants being dominant, and indeed, the original replicators had been entirely replaced.

  59. #59 CyberLizard
    January 12, 2009

    You all are missing the point. This is really scientific proof that homosexuality goes against nature! All you have to do is look at the diagram. A clearly has a penis whereas B does not. Then they mate and have little E’s. Clearly the molecular root of heterosexuality.

  60. #60 raven
    January 12, 2009

    It makes sense to separate abiogenesis from evolution.

    1. Abiogenesis is life from nonlife.
    We know little about abiogenesis although that is slowly changing. It is inherently hard to study something that happened once 3.6 billion years ago.

    2. Evolution is life changing through time.
    It is a well understood fact and theory. It is ongoing today all around us, ubiquitous. The average human as ca. 150 mutations compared to their parents.

    The definitions are separate enough and the subjects diferent enough to separate them. This is not to say that evolution has nothing to do with abiogenesis, the subjects are clearly related. Evolution would play a critical role in abiogenesis when there are self replicators. Right about now in the experiment above.

    As a practical strategy, it shuts creos down. They like to ignore evolution to pick on abiogenesis because one is bullet proof while the other is a much less well understood phenomena.

    This is the current trend in biology, to separate the two. And if anyone wants to disagree fine. I don’t care though, this subject has been beaten to death and is now in the realm of opinions that won’t change and not worth (my) time worrying about.

    PS Very key experiment. Self replicators that evolve. More complexity from less, something creos claim is impossible even though it happened to them when they started as a 1 cell zygote and ended up as a 150 pound moron.

    This is something creos always said couldn’t happen without a supernatural being’s involvement. Hmmm, do Lincoln and Joyce have wings and haloes? LOL

  61. #61 Cheshire
    January 12, 2009

    So…another paper ignored by DI, AIG et.al.

    This is some really cool stuff.

    As for the whole ‘teh complexytiez’ thing…the fad of the decade seems to be substituting ‘teh infurmashunz’ for ‘teh complexytiez’. It all works in a similar way as I understand it, so it’s equally vacuous.

  62. #62 Steve
    January 12, 2009

    Thank you for posting that, professor. I’m sure it will end up as a widely underreported story, unfortunately.

  63. #63 arvind
    January 12, 2009

    In other news, I seemed to have skipped the philosophical debate in order to point out some overlooked/forgotten details. Why does this not surprise me?

    Amy,
    If it weren’t for scientists overlooking the philosophical debate to point out that the philosophical difference is just 10 nucleotides, we wouldn’t have anything but philosophical debates. :-)

  64. #64 David Marjanovi?, OM
    January 12, 2009

    Anyone have an idea which abiogenesis niche this is most likely to occur in (e.g. deep ocean vents, sub-surface clays, hydrogenated diamonds, etc.)?

    Try it out. :-|

  65. #65 Marc Abian
    January 12, 2009

    PZ

    E and E’ differ in the sense of the RNA strands, one having the same sequence in the 3′?5′ direction as the other has in the 5′?3′ direction.

    Excuse me professor brainiac, but won’t that just cause them to bind to each other and end the reaction?

  66. #66 Cannabinaceae
    January 12, 2009

    Marc Abian:

    RNA is extremely prone to forming secondary (and tertiary) structures, which would inhibit their annealing to form double stranded RNA. In fact, it is this higher order structure that is responsible for the enzymatic capabilities of ribozymes. Unless you heated the reaction to a high enough temperature to fully denature the RNA, and then slowly reduced the temperature, the complementary strands will be unlikely to anneal.

  67. #67 profweird
    January 12, 2009

    @ Marc Abian

    Excuse me professor brainiac, but won’t that just cause them to bind to each other and end the reaction?

    As SHOWN IN FIGURE A, E and E’ do indeed bind to each other.

    But the binding is NOT permanent – they can dissociate and act as scaffolds for A/B and A’/B’ to anneal to form new E and E’ (also shown in Figure A). How often they dissociate (and how long they are annealed together) depends on temperature, salt concentration, relative concentration of A,A’, B, B’ etc.

    So E annealing to E’ is not the absolute ‘reaction stopper’ you think it is.

  68. #68 Marc Abian
    January 12, 2009

    But isn’t that the basis of inhibitory RNA regulation and anti-sense gene silencing?

    Also, the diagram with the RNA sequence seems to suggest the do pair off.

  69. #69 Scott
    January 12, 2009

    Louis, (@#51)
    When you find an HTML feature of interest on a web page, select “Source” from the “View” menu of your browser, and it will show you all of the HTML. Search for the text of interest, copy, edit, and paste.

    Scott
    —–

  70. #70 Marc Abian
    January 12, 2009

    But isn’t that the basis of inhibitory RNA regulation and anti-sense gene silencing?

    Also, the diagram with the RNA sequence seems to suggest they do pair off.

  71. #71 Tiskel
    January 12, 2009

    Marc @70:

    The diagram is showing that they catalyze one another, being paired at the time that either the E paired with one A’ and one B’ to then make an E’ or the E’ paired with an A and a B to make an E. Of course they are ‘paired’ at that moment – they just completed making the one they are connected to. And then, they separate and each catalyze another reciprocal, thus the exponential growth in the presence of the requisite substrates.

  72. #72 Rickey
    January 12, 2009

    Boy, oh Boy, oh Boy!!!!!

  73. #73 prof weird
    January 12, 2009

    marc : But isn’t that the basis of inhibitory RNA regulation and anti-sense gene silencing?

    Those are both complex, multi-enzyme systems.

    Inhibitory RNA can bind to DNA or RNA to inhibit either production of mRNA, or affect the stability of the mRNA, or translation of an mRNA into protein.

    Anti-sense gene silencing happens when long dsRNA encounters the Dicer protein (which cuts it into 20 or so base long pieces), which are used by another system (RISC) to target a certain mRNA for degradation.

    Has the neat effect that researchers can silence any gene they want by simply expressing a small 22 or so base long hairpinned dsRNA sequence from their target mRNA, and then let the cell do all the rest.

    For the experiments the researchers were doing, gene-silencing and inhibitory RNA effects not overly relevant (given that there is no Dicer, RISC, ribosomes, etc present).

    Also, the diagram with the RNA sequence seems to suggest they do pair off.

    They do, but ‘annealed’ does NOT mean ‘irreversibly bound together’. This seems to be a common idea among ‘critics’ of abiogenesis research – they may accept that a 60mer replicator can arise, but they seem to think that once it goes double stranded, it is FOREVER out of the pool because it is ‘stuck’ to its complementary strand.

    At low temperatures, E and E’ would spend nearly all the time annealed together, and rarely split into single strands;

    at high temperatures, E and E’ would spend nearly all their time single-stranded, and rarely annealed.

    All that is required for the reaction (A + B to E’) to proceed is that the complex E/E’ melt into E and E’ at least some of the time.

    Given how small they are (and number of mismatches and gaps), they would probably spend quite some time single-stranded.

    Also have concentration effect : early on, there may be millions of A,A’, B and B’ to every E and E’.

    Once E and E’ melt apart, they are FAR more likely to encounter A+B before they encounter their complement.

  74. #74 The Science Pundit
    January 12, 2009

    prof weird @#73

    At low temperatures, E and E’ would spend nearly all the time annealed together, and rarely split into single strands;

    at high temperatures, E and E’ would spend nearly all their time single-stranded, and rarely annealed.

    Obviously there must be an ideal temperature where they’re annealed just long enough to move the catalysis at maximum speed.

    I’m also assuming from that that the annealing is exothermic and the splitting endothermic. Or do I have it backwards? Or is it actually dependent upon the base sequence? The energy difference can’t be that big though, or else cells would have major energy management issues just to keep ribosomes working. I don’t know; I’m just asking.

  75. #75 prof weird
    January 12, 2009

    prof weird @#73

    At low temperatures, E and E’ would spend nearly all the time annealed together, and rarely split into single strands;
    at high temperatures, E and E’ would spend nearly all their time single-stranded, and rarely annealed.


    Obviously there must be an ideal temperature where they’re annealed just long enough to move the catalysis at maximum speed.

    For the experiment shown, being single-stranded would keep the reaction going at maximum speed (enables annealing with A and B long enough to link them into a new E’).

    I’m also assuming from that that the annealing is exothermic and the splitting endothermic. Or do I have it backwards? Or is it actually dependent upon the base sequence?

    Dependent upon bases and sequence – G:C is a stronger bond than A:T (a rough guide for figuring out melting temp of short oligos is 4 degrees for every G/C, 2 degrees for every A/T).

    The truly hideous (but more accurate) math considers sequence : ACCATGG has slightly different kinetics than GACACTG (and a slightly different melting temperature), despite having the same nucleotides.

    Mismatches – like gaps and such – lower the expected melting temp.

    AFAIK, there are two rates governing binding : the forward reaction (annealing), and the reverse reaction (melting back to single strands). At a given energy, both can happen, but one rate will be higher than the other (will melt faster than anneal, or anneal faster than melt).

    In other words, spend most of their time as single-strands, or spend most of the time annealed.

    The energy difference can’t be that big though, or else cells would have major energy management issues just to keep ribosomes working. I don’t know; I’m just asking

    Ribosomes – the protein/RNA complexes that build proteins by ‘reading’ mRNA – are powered by GTP.

    Codon/tRNA recognition is only 3 bases – they don’t anneal for very long. But then again, they don’t have to.

    But even in this case, the correct tRNA stays in the pocket longer than a mismatch.

  76. #76 Holler
    January 13, 2009

    Gee, scientists used evolutionary processes to design optimal structures. Intelligent use of evolutionary processes (RV + NS) as a means to an end. Evolutionary processes don’t use themselves, they can’t.

    Aren’t these results reminiscent of the Ghadiri protein, only here, they used RNA?

  77. #77 Stephen Wells
    January 13, 2009

    What does “Evolutionary processes don’t use themselves” even mean? Evolutionary processes _happen_.

  78. #78 Cannabinaceae
    January 13, 2009

    What does “Evolutionary processes don’t use themselves” even mean? Evolutionary processes _happen_.

    It means that Holler hasn’t demonstrated that hesheit knows anything useful about “evolutionary processes,” or even “processes” for that matter.

    The same idea-chain (can’t call it reasoning) would be useful in defending intelligent falling. “Gee, scientists intelligently used gravitational processes to verify that objects of different mass fall at the same rate. Gravitational processes can’t use themselves. Thus XQ = ZD.”

    Who knows what the initials mean? Some sort of fake equations to make some creation-jism tract look sciency?

  79. #79 Phoenix Woman
    January 13, 2009

    Interesting. I notice a paucity of woomeisters and creationists here in this thread.

    Is this because they don’t have the knowledge needed to understand that this experiment once and for all detonates the whole “but it HAD to be designed!” hoo-ha?

    Is it because they might have this knowledge, but not enough skills to even attempt to counter it with a plausible-sounding bullshit barrage?

    Or is it because PZ’s been chucking them out faster than they can comment?

    Given his willingness to allow them to demonstrate their uncensored stupidity, I’m guessing it’s not Possibility #3, but rather a combination of Possibilities #1 and #2.

  80. #80 woodsong
    January 13, 2009

    Very cool! Let’s see more research like this!

    One thing I’d be curious about would be the results if some other compounds were added to the soup. Proteins, amines, lipids, PAHs, whatever bubbles out of a hydrothermal vent…will the replicators evolve to take advantage of these, and potentially become even more complex?

    This inquiring mind wants to know!

  81. #81 Marc Abian
    January 13, 2009

    You’ve been very helpful prof weird. If you ever need to know who says what line in the lord of the ring movies, just ask.

  82. #82 Owlmirror
    January 13, 2009

    Who knows what the initials mean? Some sort of fake equations to make some creation-jism tract look sciency?

    In the cited instance, I infer they mean Random Variation + Natural Selection. Which makes the conclusion even more nonsensical, actually. Is random not random? Is natural not natural?

    I kinda doubt that #76 was really thinking carefully about that sentence.

    I do see that Ghadiri won the 1998 Feynman Prize in Nanotechnology for work on self-organizing molecules. So that’s interesting, at least.

  83. #83 The Swiss
    January 14, 2009

    This is so cool. But, as a mathematician, I’m worried that I don’t get the first diagram. Is this the usual chemist’s notation for such catalytic reactions? If that’s the case, I don’t understand what the (double? splitting?) arrows should mean, and why the multiple occurrences of the same substances are as pictured.

    If the image is just intended to help the intuition along, I thing it fails miserably, because it really obscures the simple process it’s meant to clarify.

    Or am I missing something? (I’m no chemist and I’m ill right now… :-)

  84. #84 The Swiss
    January 14, 2009

    oh! I see CyberLizard has an explanation…

  85. #85 Dior
    January 15, 2009

    Just for the record, catalytic RNA is called a rybozime, my first area of research, discovered by Tom Cech now at HHMI.

  86. #86 John
    February 6, 2009

    I simply love it when scientists are able to express what they are doing with human words. What an exciting field of study you are in. Maybe we will succeed to create more sophisticated new life in the laboratory during my life span.

  87. #87 Quantum
    April 3, 2009

    God and evolutyion are both mute. THe idea that evolution is the only alternative to God is like saying there is only white light and its subcomponents while the vast elm spectrum waits for those who have no eyes to see them.

  88. #88 Quantum
    April 3, 2009

    Ooops I should learn to Sphell.

  89. #89 Quantum
    April 3, 2009

    The Universe is one great conversation. There is no Argument. There is only information. Only man argues with Nature.

  90. #90 Zetetic
    April 24, 2009

    @quantum
    Yes… man argues with nature whenever he invents religion to make up an answer “why” or how”, rather than using science to find the real answers.

    Evolution isn’t an alternative to god so much as an answer that doesn’t require god to be involved. It wasn’t science that created a legend and presented it as an answer for a question that nobody seriously tried to thoroughly investigate until relatively recently, it was religion.

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