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Prehistoric copier. The RNA world couldn't have existed without a ribozyme that could copy RNA molecules.

Making Copies in the RNA World

Scientists have come up with a missing piece of evidence for a primitive biological world. By mimicking evolution in the lab, they produced the first RNA enzyme that can make copies of other RNA molecules--a crucial ability in the theorized world that existed before DNA and proteins entered the scene.

The discovery nearly 2 decades ago of ribozymes--RNA molecules that can catalyze chemical reactions--led to the idea that modern life might have evolved from a primitive "RNA world." Doing the job of both DNA and proteins, RNA would carry genetic information and replicate that information to pass on to future generations. But scientists have been unable to get RNA molecules to copy other RNA sequences, a job performed in the modern biochemical world by protein enzymes called RNA polymerases. That activity would be a critical component of an RNA world.

Wendy Johnston and colleagues of the Massachusetts Institute of Technology (MIT) in Cambridge exerted their own "unnatural selection" process on a collection of randomized RNA molecules. They started with a ribozyme able to perform the chemical reaction necessary for copying RNA, but unable to string together more than a couple of RNA building blocks. Then they linked copies of the mediocre ribozyme to 76-base RNAs with random sequences, hoping that one of the combinations would produce the key ribozyme.

The selection came when the researchers screened the collection for those molecules that could make a matching copy of an RNA "template." They picked the best ones and retested them with different templates. After multiple rounds of test tube "survival of the fittest," the researchers ended up with a ribozyme that could make accurate copies of RNA sequences up to 14 bases long. Most important, it could copy any RNA sequence, an ability that would be critical for a replicating ribozyme in an RNA world.

The finding removes any doubt that RNA is up to the task of synthesizing RNA molecules, says Gerald Joyce of the Scripps Research Institute in La Jolla, California. But further tweaking will be necessary to find the real "engine of the RNA world," which would have to do better than 14 bases, he notes.

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