RNA Formation Strengthened

Posted: May 15, 2009 in Evolution, News, Science, Technology
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brain.jpgRNA is one of the more basic fundamental ingredients needed for life as we know it, at least that is what science has been saying for some time now.  One of the components of RNA something called a ribonucleotide which, until now, had proven impossible to recreate in a laboratory. Now some clever little scientists have done just that, using the conditions found on an early Earth as a basis; this acts as rather impressive evidence for the scientific advancement and evolution of life.

Life’s First Spark Re-Created in the Laboratory

Researchers synthesized the basic ingredients of RNA, a molecule from which the simplest self-replicating structures are made. Until now, they couldn’t explain how these ingredients might have formed.

“It’s like molecular choreography, where the molecules choreograph their own behavior,” said organic chemist John Sutherland of the University of Manchester, co-author of a study in Nature Wednesday.

RNA is now found in living cells, where it carries information between genes and protein-manufacturing cellular components. Scientists think RNA existed early in Earth’s history, providing a necessary intermediate platform between pre-biotic chemicals and DNA, its double-stranded, more-stable descendant.

However, though researchers have been able to show how RNA’s component molecules, called ribonucleotides, could assemble into RNA, their many attempts to synthesize these ribonucleotides have failed. No matter how they combined the ingredients — a sugar, a phosphate, and one of four different nitrogenous molecules, or nucleobases — ribonucleotides just wouldn’t form.

Sutherland’s team took a different approach in what Harvard molecular biologist Jack Szostak called a “synthetic tour de force” in an accompanying commentary in Nature.

“By changing the way we mix the ingredients together, we managed to make ribonucleotides,” said Sutherland. “The chemistry works very effectively from simple precursors, and the conditions required are not distinct from what one might imagine took place on the early Earth.”

Like other would-be nucleotide synthesizers, Sutherland’s team included phosphate in their mix, but rather than adding it to sugars and nucleobases, they started with an array of even simpler molecules that were probably also in Earth’s primordial ooze.

They mixed the molecules in water, heated the solution, then allowed it to evaporate, leaving behind a residue of hybrid, half-sugar, half-nucleobase molecules. To this residue they again added water, heated it, allowed it evaporate, and then irradiated it.

At each stage of the cycle, the resulting molecules were more complex. At the final stage, Sutherland’s team added phosphate. “Remarkably, it transformed into the ribonucleotide!” said Sutherland.

According to Sutherland, these laboratory conditions resembled those of the life-originating “warm little pond” hypothesized by Charles Darwin if the pond “evaporated, got heated, and then it rained and the sun shone.”

Such conditions are plausible, and Szostak imagined the ongoing cycle of evaporation, heating and condensation providing “a kind of organic snow which could accumulate as a reservoir of material ready for the next step in RNA synthesis.”

Intriguingly, the precursor molecules used by Sutherland’s team have been identified in interstellar dust clouds and on meteorites.

“Ribonucleotides are simply an expression of the fundamental principles of organic chemistry,” said Sutherland. “They’re doing it unwittingly. The instructions for them to do it are inherent in the structure of the precursor materials. And if they can self-assemble so easily, perhaps they shouldn’t be viewed as complicated.”

RNA world easier to make

An elegant experiment has quashed a major objection to the theory that life on Earth originated with molecules of RNA.

John Sutherland and his colleagues from the University of Manchester, UK, created a ribonucleotide, a building block of RNA, from simple chemicals under conditions that might have existed on the early Earth.

The feat, never performed before, bolsters the ‘RNA world’ hypothesis, which suggests that life began when RNA, a polymer related to DNA that can duplicate itself and catalyse reactions, emerged from a prebiotic soup of chemicals.

“This is extremely strong evidence for the RNA world. We don’t know if these chemical steps reflect what actually happened, but before this work there were large doubts that it could happen at all,” says Donna Blackmond, a chemist at Imperial College London.

Molecular choreography

An RNA polymer is a string of ribonucleotides, each made up of three distinct parts: a ribose sugar, a phosphate group and a base — either cytosine or uracil, known as pyrimidines, or the purines guanine or adenine. Imagining how such a polymer might have formed spontaneously, chemists had thought the subunits would probably assemble themselves first, then join to form a ribonucleotide. But even in the controlled atmosphere of a laboratory, efforts to connect ribose and base together have met with frustrating failure.

The Manchester researchers have now managed to synthesise both pyrimidine ribonucleotides. Their remedy is to avoid producing separate ribose-sugar and base subunits. Instead, Sutherland’s team makes a molecule whose scaffolding contains a bond that will turn out to be the key ribose-base connection. Further atoms are then added around this skeleton, which unfurls to create the ribonucleotide.

The final connection is to add a phosphate group. But that phosphate, although only a reactant in the final stages of the sequence, influences the entire synthesis, Sutherland’s team showed. By buffering acidity and acting as a catalyst, it guides small organic molecules into making the right connections.

“We had a suspicion there was something good out there, but it took us 12 years to find it,” Sutherland says. “What we have ended up with is molecular choreography, where the molecules are unwitting choreographers.” Next, he says, he expects to make purine ribonucleotides using a similar approach.

The start of something special?

Although Sutherland has shown that it is possible to build one part of RNA from small molecules, objectors to the RNA-world theory say the RNA molecule as a whole is too complex to be created using early-Earth geochemistry. “The flaw with this kind of research is not in the chemistry. The flaw is in the logic — that this experimental control by researchers in a modern laboratory could have been available on the early Earth,” says Robert Shapiro, a chemist at New York University.

Sutherland points out that the sequence of steps he uses is consistent with early-Earth scenarios — those involving methods such as heating molecules in water, evaporating them and irradiating them with ultraviolet light. And breaking RNA’s synthesis down into small, laboratory-controlled steps is merely a pragmatic starting point, he says, adding that his team also has results showing that they can string nucleotides together, once they have formed. “My ultimate goal is to get a living system (RNA) emerging from a one-pot experiment. We can pull this off. We just need to know what the constraints on the conditions are first.”

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<p>Shapiro sides with supporters of another theory of life’s
origins – that because RNA is too complex to emerge from small
molecules, simpler metabolic processes, which eventually catalysed the
formation of RNA and DNA, were the first stirrings of life on Earth. </p>
<p>”They’re
perfectly entitled to disagree with us. But having got experimental
results, we are on the high ground,” says Sutherland.</p>
<p>”Ultimately,
the challenge of prebiotic chemistry is that there is no way of
validating historical hypotheses, however convincing an individual
experiment,” points out Steven Benner, who studies origin-of-life
chemistry at the Foundation for Applied Molecular Evolution, a
non-profit research centre in Gainesville, Florida. </p>
<p>Sutherland,
though, hopes that ingenious organic chemistry might provide an RNA
synthesis so convincing that it effectively serves as proof. “We might
come up with something so coincidental that one would have to believe
it,” he says. “That is the goal of my career.”</p>–>

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Comments
  1. alex says:

    Thanks, interesting.

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