On the origins of life…

by Jim Caryl

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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