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January 9, 2009

RNA Begets RNA

As Science's essay on the origin of life on Earth points out, many researchers think RNA was central to early life. But one challenge has been to show that RNA could make copies of itself without help from another biological molecule--DNA or proteins, for example--and that it could do this for long enough to allow evolution to gain a foothold. "That's no small feat," says molecular biologist Joan Steitz of Yale University. Yet molecular biologist Gerald Joyce of the Scripps Research Institute in San Diego, California, reports success this week in Science Express.


Credit: Gerald Joyce, Scripps Institute

Piece by piece. Researchers designed two RNA strands (blue and red) that could replicate indefinitely and evolve, showing how life could have arisen from these simple molecules.

When RNA replicates itself, it tends to make perfectly complementary copies that stick together like the jaws of a zipper. Once an RNA molecule has found its complementary match, it tends not to split off and make more copies. Joyce says his goal was to create an RNA molecule that was just unstable enough to keep replicating.

For almost a decade, his team played with different combinations of the four RNA nucleotides--A, U, G, C--to create an RNA that would replicate indefinitely. Nothing kept dividing. But finally, Joyce's team hit on the idea of creating an RNA molecule that would replicate by copying and assembling whole chunks of molecule at a time rather than working letter by letter. They engineered two such RNA molecules, called E and E-prime, and dropped them into a solution with four strands of nucleotides, precursors that might have been available on the young Earth. Within an hour, the number of RNAs had doubled, and the molecules kept replicating until all the other nucleotides in the solution had been used up, the researchers report. The replicated RNAs aren't perfect copies, and Joyce's team has shown that some of these mutants can outcompete their parent RNAs, becoming more populous over time. Despite being simple--the RNAs are just 70 nucleotides long--they demonstrate primitive evolution, Joyce points out.

Although the work almost certainly doesn't reflect what happened at the start of life, it models how self-replication and mutation might have arisen--a significant accomplishment, says Andy Ellington, a molecular biologist at the University of Texas, Austin.

—Rachel Zelkowitz

Rachel Zelkowitz is a science writer in Washington, D.C.


I've seen a great movie about Indoeuropeans (found it at rapidshare SE ). So RNA played an important role in finding out a lot of interesting facts about them.

Submitted by Gerald Joyce:
Yes, this a "word-by-word" copying, but some have suggested (e.g. James &
Ellington, Origins Life Evol. Biosph. 29, 375-390, 1999) that the earliest
replicators on Earth were oligo ligators, rather than polymerases. However,
the "words" (oligos) in our experiments are too long to be prebiotically
plausible. Yes, there is actual replication (autocatalytic behavior) as
opposed to mere joining (non-autocatalytic behavior), with the former
dominating by many orders of magnitude (see Paul & Joyce, PNAS 99,
12733-12740, 2002). It would indeed be interesting to shred the replication
products to recycle the raw materials, but the hitch is that the shredded
pieces would need to be reactivated, reinstalling the 5'-triphosphate that
drives the reaction. This would need to be done using phosphorylase enzymes
that are part of the replicating system.

Joyce was only able to get the RNA strands to replicate by engineering the RNA molecules to copy "word-by-word" rather than letter-by-letter. But if that is not how RNA is usually replicated, why think this experiment tells us anything about how RNA might have been able to self-replicate on the early Earth, and how life got started? I'm just not seeing how this experiment contributes to our understanding of how life originated. If anything, it seems to demonstrate that for RNA to replicate on its own it requires an intelligent agent to manipulate it into acting in ways it does not act in nature.

Was there actual replication of the original E and E-prime RNA strands, or was there a mere joining reaction of those strands with the nucleotides present in teh solution?

It would be interesting to have this replication reaction take place in the presence of a low concentration of an RNA-shredding enzyme, to recycle the raw materials and allow the process to continue indefinitely.

I wonder, though, how quickly the RNAs would evolve resistance to the enzyme....

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