On the origins of life…

Research bloggingTODAY’S edition of Nature (14 May 2009) features a landmark paper from researchers at the University of Manchester School of Chemistry that describes the synthesis of a pyrimidine ribonucleotide from simple chemicals, which may have existed on an early Earth. The research by Matthew Powner, in the laboratory of John Sutherland, represents a major stepping stone in support of the ‘RNA World’ theory, which describes the origins of life as passing through a stage in which RNA was the sole mediator of inheritance and catalysis, i.e. no DNA or proteins.

You can learn more about RNA World theory at the Exploring Origins website, or via resources on the website of Jack Szostak, one of the pre-eminent leaders in the field who also presents an accompanying perspective in this edition.

Whilst RNA is certainly a versatile molecule, with one form or another capable of breaking itself apart, joining itself to other RNA molecules, promoting formation of peptide linkages (the primary links of proteins) and templating its own self-replication, a major limiting point has existed regarding the origins of the necessary precursors for the RNA itself, i.e. ribonucleotides. Since the late 60’s, chemists studying prebiotic chemistry have focussed on trying to identify conditions in which these ribonucleotides would spontaneously assemble from their constituent parts: a nucleobase (which can be adenine, guanine, cytosine or uracil), a ribose sugar and phosphate. However, this approach was based on the assumption that these sub-units would assemble first, before combining to form the ribonucleotides. Unfortunately, no realistic conditions have been found in which a nucleobase would join to a ribose sugar.

This is perhaps not surprising given that early-Earth was not like the organised and refined laboratory of a research chemist, where compounds of high purity are available for stepwise mixing. Thus, Sutherland’s group have taken a new and innovative tack by exploring a route in which the sugar-nucleobase emerges from a common precursor, in a process facilitated by the presence of the third sub-unit, phosphate. Whilst the phosphate does not become incorporated until a later step, in the early stages it acts as both a pH and chemical buffer, and as a catalyst (essentially to guide the formation of the correct bonds), whilst also preventing degradation of a key intermediate both directly, and indirectly (by depletion of unwanted by-product).

The final reactions see the phosphate added, but this too is facilitated by a co-product of an earlier reaction, which itself benefited from a phosphate-catalysed process. The whole system appears harmonious, highlighting the importance of using mixed chemical systems in which reactants for one reaction step also control other steps. The final flourish is the ability to remove unwanted by-products from the final ribonucleotide using UV light, something that would have been plentiful in an early-Earth, and which by quirk of chemistry appears not to damage the final product.

The authors finish by commenting, ‘Our findings suggest that the prebiotic synthesis of activated pyrimidine nucleotides should be viewed as predisposed’. Whilst it is impossible to truly validate a historical origins theory, the hope is that having established that the necessary reactions are at least possible, that the propensity for these reactions to occur might become self-evident proof of their occurrence. They have also wittingly established a new system of approach by which the synthesis of the complementary partner of the pyrimidine ribonucleotides, namely purine ribonucleotides, can be addressed.

Powner, M., Gerland, B., & Sutherland, J. (2009). Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions Nature, 459 (7244), 239-242 DOI: 10.1038/nature08013

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2 thoughts on “On the origins of life…

  1. A note on the origin of origins

    All Life Creates and Feeds Genes
    Genes, Genomes, Cellular Organisms All Feed Genes

    A. Gene eats gene?

    B. See Updated Life’s Manifest May 2009

    For Nature, Earth’s biosphere is one of the many ways of temporarily constraining an amount of ENERGY within a galaxy within a galactic cluster, thus avoiding, as long as possible, spending this particularly constrained amount as part of the fuel that maintains the clusters expansion.

    C. Genes are THE Earth’s organisms and ALL other organisms are their temporary take-offs

    For Nature genes are genes are genes. Genes and their take-offs are the temporary energy packages and the more of them there are the more enhanced is the biosphere, Earth’s life, Earth’s temporary storage of constrained energy. This is the origin, the archetype, of selected modes of survival.

    D. All Life Creates and Feeds Genes. Genes, Genomes, Cellular Organisms All Feed Genes.

    It is not that gene eats gene. The early genes came into being by solar energy and lived a very long period solely on solar energy. Metabolic energy, the indirect exploitation of solar energy, was a much later phase in the evolution of Earth’s biosphere.

    However, essentially it is indeed so. All Life Creates and Feeds Genes. Genes, Genomes, Cellular Organisms, All Create And Feed Genes.

    Dov Henis
    (Comments from 22nd century)

    1. Thanks for your comment Dov, but I’m just curious, is:

      All Life Creates and Feeds Genes. Genes, Genomes, Cellular Organisms All Feed Genes

      meant as a mantra? It may need some revision as you state that Genes (though I would go further and suggest RNA) are the organisms and that cells are not organisms, thus the use of ‘cellular organisms’ in the mantra is unwarranted.

      It is an interesting perspective you present, but which is essentially a revision of the Selfish Gene hypothesis set out by Richard Dawkins in the 70’s. I happen to agree with the general premise, working as I have with an RNAzyme that can both replicate itself and catalytically cleave itself. However, despite the analogy of the ‘spacecraft’, which I admit is inventive, there is nothing particularly new in this argument.

      For Nature, Earth’s biosphere is one of the many ways of temporarily constraining an amount of ENERGY within a galaxy within a galactic cluster, thus avoiding, as long as possible, spending this particularly constrained amount as part of the fuel that maintains the clusters expansion.

      I have to say that I am not sure just how much ‘energy’ life is really constraining. Certainly we know that ultimately all life, whether you consider this to be genes or the ‘spacecraft’ genes use to propagate themselves, derives from solar energy. Even life deep within the Earth, or at the bottom of oceans, that never sees sunlight and derives its energy from chemical-synthesis is still a product of an initial string of nucleic acid that will have required solar input. Life is a great store of ‘chemical energy’, but if we are really talking energy in the sense of E=mc2, then it is the mass of the Earth itself, in this context, which is the Earth’s storage of constrained energy; it being the denser and more massive.

      However, with regards to you assertion that genes are the only moieties that can be describes as an organisms, and that cells are just shells; ultimately the more advanced a cooperation is, the more complex it becomes, the more dependent the original entity becomes on the cellular environment that it has wrought.

      At this point it starts to divest responsibility for its care, uptake and replication to other machineries. As genes, in themselves, are now no longer able to survive in the absence of cells, and haven’t been able to do so for a few billion years, I don’t think it is unreasonable to consider a single-celled organism as an ‘organism’, nor a metazoan (in its entirety) as an organism (it having diversified cellular functions to specialised roles that cannot exist without their complementary other cell types).

      Furthermore, complex organisms such as mammals are dependent on their microbiome; the microbiome is the zoo of microorganisms that coat every external surface – which in a definitive sense also includes the surface of the alimentary tract – without which we would not survive (I wrote about it here in: ‘Bio-suit‘). Thus from this perspective, our genes exist due to the interaction of thousands of ‘alien’ genes, but nothing new there.

      So whilst I appreciate that from an intellectual view point, the selfish gene is the fundamental unit of life, it is the ‘space-crafts’ that have been developed for its purposes, and the ultimate inability to disentangle the former from the latter, that earns the right of any metazoan to be described an an organism.

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