In The Prebiotic Kitchen

By Carl Zimmer | May 13, 2009 1:00 pm

To explain the origin of life, scientists seek to explain the origin of its components. The three most important of these are RNA, DNA, and proteins.

Just about all life today uses DNA to encode its genetic information. The only exception are viruses that use a single-stranded version of DNA, known as RNA. The rest of us have RNA in our cells as well, but it carries out other functions. Some RNA molecules are copies of genes that our cells use as templates to build proteins; others can silence genes or act as sensors or help to build proteins. As I wrote in an essay published in Science in January, this sort of evidence has led a number of researchers to argue that life as we know it, with DNA, RNA, and proteins, started out with just RNA. In the so-called RNA world, this versatile molecule acted both like DNA (storing genetic information) and proteins (carrying out chemical reactions, such as building new RNA molecules). It’s a big hypothesis, and certainly not simple to test. No one has discovered any truly free-living RNA-based organisms, and so if the RNA World did exist once, its inhabitants may have been driven extinct when some of them gave rise to DNA-based life. And there’s another big question: if there was RNA-based life, where did the RNA come from?

One possibility is that the raw ingredients on the early, lifeless Earth reacted with each other and produced RNA. For 40 years, scientists have been investigating the chemistry of those ingredients–stuff like formaldehyde and cyanide–to see if they could indeed combine into the first biological molecules. It’s been quite a struggle–but it turns out that it was a struggle the scientists brought upon themselves. They tried to make RNA the obvious way, but nature doesn’t care what we consider obvious.

RNA is a word-like molecule, with four different letters that can be combined into a vast variety of strings. Each letter is called a ribonucleotide. It has two parts. One part lets the ribonucleotide bind to the ribonucleotides on either side, to form a backbone. It’s made of phosphate and a sugar called ribose. The other part is the nucleobase, which comes in four different forms and encodes genetic information.

makingrnasharp.jpgSo it seemed obvious that if indeed RNA emerged on the early Earth, its two parts must have emerged first. Scientists discovered reactions that suggested that nucleobases can indeed form from prebiotic molecules, as can the riboose-phosphate backbone. But when it came time to join together the two parts, the scientists hit a wall. The two molecules just don’t like each other much. Their dislike of each other led some scientists to look into the possibility that life did not start out with RNA, but with another molecule that doesn’t exist anywhere on Earth today. Later, RNA replaced that mystery molecule, and then later still DNA and protein evolved.

But as I explained in my Science essay, University of Manchester John Sutherland thought it was too soon to rule out the possibility that life had started out with RNA. He began to look for other routes from prebiotic chemistry to RNA besides the obvious one. Today, in Nature, he and his colleagues report that they found it.

In their paper, they published a kind of chemical road map that sums up what they did. Don’t be put off–I’ll explain the lay of the land below.


The blue arrows represent the obvious route to RNA, going from prebiotic compounds (marked here by 7,8, and 10) to nucleobases (3) and ribose (4). And the big red X shows the point at which this route fails.

Sutherland and his colleagues started with the same ingredients, but cooked them in a different recipe, marked in green. Instead of trying to build the two parts independently, the scientists instead built a single molecule that had more and more components of the two parts already in place. They used just four reactions, all of which worked efficiently, to get one of the four ribonucleotides, known as cytidine. At the end of the process, the scientists zapped the mix with ultraviolet light (something that would be easy to come by on the early Earth, unprotected by an ozone layer). They eliminated some of the unwanted side products and turned some of the cytidine into another unit of RNA, known as uracil.

In an accompany commentary, Jack Szostak of Harvard calls this experiment a “tour de fource.” Of course, it doesn’t answer all the questions about the RNA World–for starters, scientists still have to synthesize the other two letters in RNA’s alphabet. But it does show how careful scientists must be not to declare things impossible. Sometimes they just need to redraw the map.


Powner et al, “Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions,” Nature 2009, 459:239  doi:10.1038/nature08013

Jack Szostak, “Systems chemistry on early Earth,” Nature 2009, 459:171 

[Image: MuppetWiki]

CATEGORIZED UNDER: Evolution, Microcosm: The Book

Comments (27)

  1. Carl,

    This is a wonderful summation. When I was in High School in the 70s the work of Sidney Fox suggested that prebiotic amino acids could have formed proteinoids. Proteinoids in water form globular structures called microspheres that show many of the properties of living cells.

    I wonder if such microspheres could have enclosed the primitive RNA molecules, allowing them the space and stability for their necessary catalytic reactions?


  2. Hi, Carl, This is very exciting. It might be an evolutionary companion to an article by Robert Shapiro in the June, 2007 Scientific American. Shapiro outlines an “energy-driven” initiation of life, which he terms “metabolism first.” Droplets bounded by primitive membranes (perhaps the microspheres described above by Richard Gayle) acquire useful compounds that react to supply energy to a slowly evolving series of growth stages. These droplets acquire compounds at random from the environment, some useful some not. Perhaps some of the randomly acquired compounds could be the ones you describe here.

  3. John Lynch

    Hi Carl,
    Thanks for an interesting piece. I’m confused in your initial description of RNA as a sugar combining with a phosphate compound– I see the Ribose sugar in your diagram, but the amino compound “nucleobase” hasn’t a phosphate group or phosphorus atom to be seen. My organic chemistry is very rusty, but is there something I’m missing?

  4. Lello Islam

    Excellent summation of the research.

    With all due respect to Dr. Robert Shapiro, who has been commentating on this recently published work, and who advocates the ‘Metabolism’ first hypothesis, this is a piece of work that is purely experimental with little or no hypothetical conjecture.

    Is it not true that we have to base science on facts? It is very easy to be cynical and criticise work, but if one does need to oppose one theory and propose an alternative, as Dr Shapiro has done in this case, should it not be backed up with some sort of evidence?

    Indeed it is true that Professor Eschenmoser once stated, and forgive me if it is slightly misworded, that:

    ‘The origins of life cannot be rediscovered, it must be reinvented’.

    Let us say that this work is an example of what MAY have happened. What has been shown in this research may have not been the case. We will never know, but it is a strong contribution of what may have taken place on primordial earth. I call on those who would like to contest the ‘RNA world’ or an ‘RNA world + X’ hypothesis to disclose some sort of evidence otherwise.

  5. captain Kidd

    Understanding how life emerged on Earth is one of the greatest challenges facing modern chemistry. A new way of looking at the synthesis of RNA sidesteps a thorny problem in the field.

    They are on a fool’s errand.

    Cosmic Ancestry (panspermia) answers most of the questions WRT the origin of life on earth.

  6. Lello Islam

    What do you mean by ‘side step’? Do you mean that we should take ribose, a nucleobase, and phosphate and then stick them together?

    It’s been tried and it doesn’t work. Which means it happened in another way. This work isn’t a ‘side step’, it’s an alternative way of the first few steps to getting to RNA.

    Panspermia? Please provide some sort of evidence. An iota of it would be a start.

  7. I haven’t read the article yet. I can’t concentrate enough. The duck on the right side of the first diagram keeps distracting me.

  8. captain Kidd

    “Panspermia? Please provide some sort of evidence. An iota of it would be a start.”

    Start here:

    That should keep you busy for a while!!

  9. Panspermia = “it’s turtles all the way down”

  10. SteveC

    Panspermia? That doesn’t answer the question. It just moves it.

  11. Mel

    Captain Kidd, that website appears to just link to whatever the person who maintains it thinks supports his position regardless of what is linked to actually says. I see a lot of titles of recent journal articles that have nothing to do with panspermia, and can only be linked to it by very contorted thinking. Frankly, it reeks of a person who has decided what the absolute truth is, and thus tries to fit the world to that notion. That isn’t science – it is bad post hoc reasoning of the sort found in creationism and conspiracy theories. Try linking to some peer-reviewed papers that explicitly test predictions from panspermia and give actual evidence for it.
    And in any case, SteveC is correct: you are just moving the question. Life had to start somewhere, and wherever it started, the question remains as to how. Panspermia does not even start to get at that question (even when it is a seriously address hypothesis, which it certainly is not at that website to which you referred everyone).

  12. Lello Islam

    Still not convinced by Panspermia. I’ve just visited the website, and it’s full of comments about this work being orchestrated by Obama…….please.

    This work has been ongoing for years. The conspiracy theories merely make me laugh, and smells of pathetiscm (even though it’s not a real word I shall use it here). This is a bit like a bomb dropping on the heads of a creationist, metabolist or whatever other theory you believe in.

    Give me some hard facts, I’m open minded and ready to be convinced.

  13. Q ball

    Thanks for this one, Carl! I love the “origins” stuff. Your proto-ribosome and viroid pieces were fantastic, and this one’s a real gem. Keep ’em coming!

  14. Torbjörn Larsson, OM

    Nice writeup!

    In the so-called RNA world, this versatile molecule acted both like DNA (storing genetic information) and proteins (carrying out chemical reactions, such as building new RNA molecules).

    One hypothesized task I’ve seen is that RNA acts to concentrate and activate mono- or diamino acids, which likely preceded it. It is probable that in prebiotic chemistry a little bit of ‘everything’ happened simultaneously.

    That is by the way a prediction that this result tests positive for as phospate isn’t just an afterthought but contribute to the result. In the same sense, what is then less promising is that I hear they still had to purify in between steps.

    Now I wonder if they could simplify (well, sort of since 4 reactions is really simple) by using glycine instead of ribose as backbone. GNA is a putative pre-RNA compound, doing the same task with an even simpler molecule. Again, perhaps initially both GNA and RNA was in play.

  15. Sili

    This reminds me of how the initial attempt at synthesising vitamin B12 failed due to the wrong choice of retrosynthesis.

    Years of work making two halves that then could not be joined.

  16. Lello Islam

    Agreed about retrosynthetic analysis. The problem with the earlier attempts to make ribonucleotides has been retrosynthetic analysis. Yes, RNA is structurally and constitutionally more difficult at first look, merely because the number of atoms in it, as well as the stereochemical complexity (i.e it’s three dimensional shape), but in terms of chemistry so far it has been demonstrated to be generated quite efficiently. GNA has yet to be demonstrated to be created prebiotically. Just because something looks simple, doesn’t mean it’s easier to make. Likewise, the same problem exists with other ‘minimal’ nucleic acids such as PNA and TNA.

    With respect to RNA and amino acids, a nice paper was published by Sutherland and Mullen I think in 2007 in a german chemistry journal, Angewandte Chemie, where they activate ribonucleotides, as well as make amino acid amides.

  17. Dov Henis

    Unbelievable! Origin Of Life Pre-Metabolism?
    The Wheel has Just Been Reinvented!
    Read All About It!

    What Came First in the Origin of Life? New Study Contradicts the ‘Metabolism First’ Hypothesis

    Dov Henis
    (Comments From The 22nd Century)
    Updated Life’s Manifest May 2009
    28Dec09 Implications Of E=Total[m(1 + D)]
    Cosmic Evolution Simplified

    PS: Just reflect about sleep and chirality… DH

  18. Dov Henis

    Life IS INDEED An RNA World

    Genomes Are RNAs’-Made Patterns-Manuals

    “Repeats protect DNA”

    “More On Evolution In The Still RNA World”

    Fitting together the pieces of the “still an RNA world” puzzle ?

    – Rational probability and possibility that the initial, independent pre-biometabolism direct sunlight-fueled genes (life) were RNAs, who evolved their DNA-images as operational patterns-manuals libraries, and celled and genomed them. They most probably synthesized (and nucleusized) their DNAs manual libraries as their functional organs, to serve as their environmentally stabler than RNA, than themselves, works memory cores.

    – Rational possibility that ALL RNAs represent the original archae-genes that since their (life) genesis have been and still are the primary actors, assessors, messengers, operators of all life processes.

    – Rational possibility that the RNAs are the environmental feedback communicators to, and modifiers of, the genomes, that the RNAs are the effectors of the desirable biased genes expressions modifications, of enhanced energy constraining for survival.

    Dov Henis
    (Comments From The 22nd Century)
    28Dec09 Implications Of E=Total[m(1 + D)]
    Cosmic Evolution Simplified

  19. Dov Henis

    03.2010 Updated Life Manifest

    Update of

    Recapitulation of some earlier notes on the
    Scientific Comprehension Of The Origin, Drive, Nature And Purpose Of Life

    A. Uniqueness Of science among human artifacts

    ALL aspects of our culture are, of course, anthropoartifacts, including science. Yet among those artifacts science has a distinct uniqueness for us.

    During the recent several centuries in the course of human history humans have been developing science at an accelerating rate as a provider of convincing, ever closer approaching, approximate models of the real world.

    B. Origin and nature of life

    28Dec09 Implications Of E=Total[m(1 + D)]

    Astronomically there are two “physics”, a “classical physics” system of and between galactic clusters, and a “quantum physics” system WITHIN the galactic clusters.

    The onset of big-bang’s inflation started gravity, followed by formation of galactic clusters that behave as accelerating Newtonian bodies while continuously reconverting their shares of pre-inflation masses back to energy, that continuously fuels their ongoing expansion, and of endless intertwined evolutions WITHIN the clusters in attempts to resist-postpone this reconversion.

    As mass is just another face of energy it is commonsensible to regard not only life, but mass in general, as a format of temporarily constrained energy.

    It therefore ensues that whereas the in-space expanding cosmic constructs, the galaxies clusters, are – overall – continuously converting their original pre-inflation mass back to energy, the overall evolution WITHIN them, within the clusters, is in the opposite direction, temporarily constrained energy packages such as black holes and biospheres and other energy-storing mass-formats are precariuosly forming and “doing best” to survive “as long as possible”.

    C. The drive and nature of Earth life

    Earth life Genesis, formation of the first genes, was a phenomenon of serendipitous occurrence, in a supportive environment, of ‘favourably-coursed’ energy potential between in-coming sun radiation and in-water polymerizing-precipitating RNA-related oligomeric configurations.

    The drive of Earth life and of its evolution is to enhance the functionality and survivability of Earth’s genes, in order to maintain and enhance Earth-biosphere’s temporary constrained energy storage, to maintain the biosphere BIO as long as possible.

    The RNA genes are life’s prime strata organisms. They evolved their DNA-images as their organ, their continuously updated operational worklogs primal Earth’s organisms libraries, and genomed them, i.e. nucleusized them, and celled them with their other organ, the outer cell membrane.

    It is the RNA genes and their DNA replicas, life’s prime strata organisms, that evolve, and the evolution of genomes, the 2nd stratum of life, and of the 3rd life stratum cellular organisms, is an interenhancing consequence of their genes’ evolution.

    D. The formation of Earth life

    Earth Life: 1. a format of temporarily constrained energy, retained in temporary constrained genetic energy packages in forms of genes, genomes and organisms 2. a real virtual affair that pops in and out of existence in its matrix, which is the energy constrained in Earth’s biosphere.

    Earth organism: a temporary self-replicable constrained-energy genetic system that supports and maintains Earth’s biosphere by proliferating and maintenance of genes.

    Gene: the primal Earth’s organism and/or its functional DNA replicas. (1st stratum organism)

    Genome: a multigenes organism, comprising the genes operational replicas-work-patterns, an organ of the primal Earth’s genes, consisting of a cooperative commune of its member genes. (2nd stratum organism)

    Cellular organisms: mono- or multi-celled Earth organisms. (3rd stratum organism)

    E. Update of underlying life sciences conception is thus feasible

    – First were independent individual RNA genes, Earth’s primal organisms.

    – Genes aggregated cooperatively into genomes, RNA or their DNA replicas multigenes organisms, with genomes’ organs.

    – Simultaneously or consequently genomes evolved protective-functional membranes, their organs.

    – Then followed cellular organisms, with a variety of outer-cell membrane shapes and
    functionalities and a variety of inter- and intracell processes.

    This is a scientific, NOT A TECHNICAL, life-science conception.

    It is tomorrow’s comprehension of life and of its evolution.



    F. The purpose of OUR, human, life

    The purpose of OUR life and of its promotion is ours to formulate and set. It derives solely from our cognition.


    Dov Henis
    (Comments from 22nd century)

    Cosmic Evolution Simplified

  20. Very nice effect, and great tutorials thanks for sharing

    I read your blog and I feel that the information about “computer” it’s really appreciable.

    Under-Cabinet Range Hoods


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The Loom

A blog about life, past and future. Written by DISCOVER contributing editor and columnist Carl Zimmer.

About Carl Zimmer

Carl Zimmer writes about science regularly for The New York Times and magazines such as DISCOVER, which also hosts his blog, The LoomHe is the author of 12 books, the most recent of which is Science Ink: Tattoos of the Science Obsessed.


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