Artificial molecule evolves in the lab * 19:00 08 January 2009 by Ewen CallawayA new molecule that performs the essential function of life - self-replication - could shed light on the origin of all living things.If that wasn't enough, the laboratory-born ribonucleic acid (RNA) strand evolves in a test tube to double itself ever more swiftly.
"Obviously what we're trying to do is make a biology," says Gerald Joyce, a biochemist at the Scripps Research Institute in La Jolla, California. He hopes to imbue his team's molecule with all the fundamental properties of life: self-replication, evolution, and function. Joyce and colleague Tracey Lincoln made their chemical out of RNA because most researchers think early life stored information in this sister molecule to DNA. And unlike the stuff of our genomes, RNA molecules can catalyse chemical reactions.
"We're trying to jump in at the last signpost we have back there in the early history of life," Joyce says.
Molecular brewRather than start with RNA enzymes - ribozymes - present in other organisms, Joyce's team created its own molecule from scratch, called R3C. It performed a single function: stitching two shorter RNA molecules together to create a clone of itself. Further lab tinkering made this molecule better at copying itself, but this is not the same as bringing it to life. It self-replicated to a point, but eventually clogged up in shapes that could no longer sew RNA pieces together. "It was a real dog," Joyce says. To improve R3C, Lincoln redesigned the molecule to forge a sister RNA that could itself join two other pieces of RNA into a functioning ribozyme. That way, each molecule makes a copy of its sister, a process called cross replication. The population of two doubles and doubles until there are no more starting bits of RNA left.
"We just let them cook, let them amplify themselves silly," he says
Lab evolutionNot content with achieving one hallmark of life in the lab, Joyce and Lincoln sought to evolve their molecule by natural selection. They did this by mutating sequences of the RNA building blocks, so that 288 possible ribozymes could be built by mixing and matching different pairs of shorter RNAs. What came out bore an eerie resemblance to Darwin's theory of natural selection: a few sequences proved winners, most losers. The victors emerged because they could replicate fastest while surrounded by competition, Joyce says.
"I wouldn't call these molecules alive," he cautions. For one, the molecules can evolve only to replicate better. Reproduction may be the strongest - perhaps only - biological urge, yet even simple organisms go about this by more complex means than breakneck division. Bacteria and humans have both evolved the ability to digest lactose, or milk sugar, to ensure their survival, for instance. Joyce says his team has endowed its molecule with another function, although he will not say what that might be before his findings are published. More fundamentally, to mimic biology, a molecule must gain new functions on the fly, without laboratory tinkering. Joyce says he has no idea how to clear this hurdle with his team's RNA molecule. "It doesn't have open-ended capacity for Darwinian evolution."
Missing witnessA life-mimicking molecule will also need to assemble itself from simpler components than two halves, says Michael Robertson, a biochemist at the University of California, Santa Cruz. Both DNA and RNA currently replicate with the help of a protein enzyme that joins individual nucleotide "letters". Early life may have done the same, or it could have joined short stretches of RNA, Robertson says. Moreover, efforts to create more life in the labs will eventually hit a philosophical wall, not a technical one.
"If somebody makes something great in the lab, it's fantastic. But really the origin of life on Earth is an historical problem that we're never going to be able to witness and verify," he says.
Journal reference: Science (DOI: 10.1126/science.1167856)
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