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Friday, January 9, 2009

Self-Replicating Chemicals Evolve Into Lifelike Ecosystem

By Alexis Madrigal


Life makes more of itself.

And now so can a set of custom-designed chemicals. Chemists have shown that a group of synthetic enzymes replicated, competed and evolved much like a natural ecosystem, but without life or cells.

"So long as you provide the building blocks and the starter seed, it goes forever," said Gerald Joyce, a chemist at the Scripps Research Institute and co-author of the paper published Thursday in Science. "It is immortalized molecular information."

Joyce's chemicals are technically hacked RNA enzymes, much like the ones we have in our bodies, but they don't behave anything like those in living creatures. But, these synthetic RNA replicators do provide a model for evolution — and shed light on one step in the development of early living systems from on a lifeless globe.

Scientists believe that early life on Earth was much more primitive than what we see around us today. It probably didn't use DNA like our cells do. This theory of the origin of life is called the RNA World hypothesis, and it posits that life began using RNA both to store information, like DNA does now, and as a catalyst allowing the molecules to reproduce. To try to understand what this life might have looked like, researchers are trying to build models for early life forms and in the process, they are discovering entirely new lifelike behavior that nonetheless isn't life, at least as we know it.

As Joyce put it, "This is more of a Life 2.0 thing."

The researchers began with pairs of enzymes they've been tweaking and designing for the past eight years. Each member of the pairs can only reproduce with the help of the other member.

"We have two enzymes, a plus and a minus," Joyce explains. "The plus assembles the pieces to make the minus enzyme, and the minus enzyme assembles the pieces to draw the plus. It's kind of like biology, where there is a DNA strand with plus and minus strands."

From there, Joyce and his graduate student Tracey Lincoln, added the enzymes into a soup of building blocks, strings of nucleic bases that can be assembled into RNA, DNA or larger strings, and tweaked them to find pairs of enzymes that would reproduce. One day, some of the enzymes "went critical" and produced more RNA enzymes than the researchers had put in.

It was an important day, but Joyce and Lincoln wanted more. They wanted to create an entire population of enzymes that could replicate, compete and evolve, which is exactly what they did.

"To put it in info speak, we have a channel of 30 bit capacity for transferring information," Joyce said. "We can configure those bits in different ways and make a variety of different replicators. And then have them compete with each other."

But it wasn't just a bunch of scientist-designed enzymes competing, like a miniature molecular BattleBots sequence. As soon as the replicators got into the broth, they began to change.

"Most of the time they breed true, but sometimes there is a bit flip — a mutation — and it's a different replicator," explained Joyce.

Most of these mutations went away quickly, but — sound familiar? — some of the changes ended up being advantageous to the chemicals in replicating better. After 77 doublings of the chemicals, astounding changes had occurred in the molecular broth.

"All the original replicators went extinct and it was the new recombinants that took over," said Joyce. "There wasn't one winner. There was a whole cloud of winners, but there were three mutants that arose that pretty much dominated the population."

It turned out that while the scientist-designed enzymes were great at reproducing without competition, when you put them in the big soup mix, a new set of mutants emerged that were better at replicating within the system. It almost worked like an ecosystem, but with just straight chemistry.

"This is indeed interesting work," said Jeffrey Bada, a chemist at the Scripps Institution of Oceanography, who was not involved with the work. It shows that RNA molecules "could have carried out their replication in the total absence" of the more sophisticated biological machinery that life now possesses.

"This is a nice example of the robustness of the RNA world hypothesis," he said. However, "it still leaves the problem of how RNA first came about. Some type of self-replicating molecule likely proceeded RNA and what this was is the big unknown at this point."

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