A New Step in Re-Creating First Life on Earth
An RNA molecule that can make copies of a variety of RNAs adds new support to the RNA-world theory.
Olena Shmahalo/Quanta Magazine
By Emily Singer
August 25, 2016
One of the biggest mysteries in the origin of life is how the first biological molecules came into being. Today’s cells use complex assemblies of biological molecules to manufacture DNA, RNA and proteins. How did life work before those molecules existed?
The predominant theory, known as the “RNA world,” proposes that RNA was the first biological molecule. RNA possesses the two essential properties needed for life: It can encode information (like DNA), and it can catalyze biological reactions (like proteins). Perhaps life began with an RNA or RNA-like molecule capable of copying itself, transmitting its genetic information to the next generation.
But the RNA-world theory has a gaping hole. Scientists have been unable to create such a molecule in the lab. Since the 1990s they’ve been able to make RNA enzymes, or ribozymes, that can make complementary copies of an RNA template — an RNA sequence like AACU could be copied into the complementary UUGA, for example. But actually replicating RNA requires two steps, moving from AACU to UUGA and then back again to AACU. Another difficulty is that existing RNA enzymes can’t make long or complex molecules.
Now, for the first time, scientists have produced an RNA enzyme that can make a wide range of RNA sequences. It can also replicate most RNA molecules up to 24 letters long. “Our ribozyme is the first one to replicate RNA in a base-by-base manner, the same way it is done in nature,” said David Horning, a researcher at the Scripps Research Institute in La Jolla, California, who did the work with Gerald Joyce, also at Scripps. The study was published this month in the Proceedings of the National Academy of Sciences.
The researchers started with an existing ribozyme and added random changes to the sequence to create a trillion slightly different versions. The researchers then subjected the pool of ribozymes to a challenge. They selected only those that were capable of making two different complex RNA molecules. They then repeated the process two dozen times — subjecting the molecules that passed each level of challenges to increasingly stringent challenges — to find the candidates that could make the 30-letter RNAs the fastest. This technique, known as experimental evolution, or test-tube evolution, is an artificial version of natural selection. Researchers introduce a few new mutations after each round of the experiment.
The molecule that made the new RNAs most efficiently, known as polymerase ribozyme 24-3, worked surprisingly well. It could synthesize a variety of RNA sequences with complex structures, not just the two from the initial tests. And it was much more efficient than the original ribozyme in making simple RNA molecules.
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