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'RNA World': Scientists Inch Closer to Recreating Primordial Life
Earth's very first living things may have relied on RNA to store genetic information.
Credit: NASA / Jenny Mottar

To figure out how life on Earth started, scientists must recreate the world as it was, or at least know the ins and outs of our primordial planet. This week, scientists moved in that direction, putting together a mix of chemicals simpler than DNA that reproduced similar molecules — a step toward actually being alive. 

Scientists studying the origin of life think that the first molecules to replicate themselves — the very first living things — lived in what is called "RNA world." The RNA world hypothesis says that before there was DNA, or deoxyribonucleic acid, there was RNA (ribonucleic acid) serving as a kind of primitive genetic material and simple enzymes. This is simpler than the protein-based chemistry that governs life today, in which the genetic material and enzymes are separate. [7 Wild Theories on the Origin of Life]

In the new study, David Horning and Gerald Joyce, both at The Scripps Institute in La Jolla, California, mixed a cocktail of water, RNA and an enzyme called ribozyme. They found that the ribozyme linked to the pieces of RNA, and in turn allowed those RNA bits to link with other chemicals called monomers, to make more RNA.

"It's the first example of nucleic acids (or genetic information in general) being replicated by anything other than a protein enzyme, and further shows that replication of genetic material could be accomplished with RNA alone, confirming part of the RNA world hypothesis," Horning told Live Science in an email.

Ribozymes have been used in biochemistry for decades. But in this experiment, Horning and Joyce took the ribozyme and made millions of variants. The idea was to have these different types of ribozyme interact with RNA in a test-tube environment. The ribozymes that could link up to RNA and form more RNA were the "survivors." Effectively, what happened was very like the natural selection process. [Extreme Life on Earth: 8 Bizarre Creatures]

The reason the resulting material isn't a fully living thing is that the ribozyme can neither duplicate itself nor any RNAs that are larger than the enzyme. Even so, the new research did show it's at least possible to make proto-life out of RNA alone. "If the polymerase is made better, it should be able to replicate itself." Essentially, the only missing piece is the right molecule to link with the RNA.

The reason this works is that like DNA, RNA is made of a specific set of chemical bases called nucleotides. They differ in their shapes. DNA is a double-stranded helix shape made of adenine, guanine, cytosine and thymine, the famous A, G, C and T of the genetic code. RNA shares three of the nucleotides with DNA; the fourth is a chemical called uracil — so the "alphabet" is A, G, C and U. Instead of making a double-helix shape, RNA comes in single strands that sometimes fold on themselves. Ribozyme links to RNA and unfolds it, which allows the nucleotides to come in contact with their complementary partners, making more RNA.

DNA replicates by coming in contact with enzymes and breaking into two strands. Because the A can link only with T, and G can link only with C, DNA can preserve its shape — the DNA molecule can only be put together in a certain way. That's why genetic information can be preserved; the DNA always duplicates itself.

Horning and Joyce's work got RNA to replicate itself, but only for a limited amount of time before it stopped. And on top of that, the process did not always reproduce exactly the same kind of RNA, nor can it make copies of molecules bigger than itself. With DNA and the enzymes that unzip the helix, that's not the case – DNA molecules are quite a bit larger than the enzymes that cut them in two.

Yet some in the field are skeptical. Parallel research last year looked at the possibilities of simple chemicals that may have worked with RNA to give life a jumpstart, notably that RNA might have worked with simple amino acids and avoided the use of complex enzymes entirely. While that work shares some characteristics with the  RNA world hypothesis, there are some differences. 

Charles Carter, of the University of North Carolina, who worked on one of those studies, said while this experiment was a "tour de force," it might not tell scientists everything they hope about the first living molecules. He said the chemicals used — ribozyme in this case — might not reveal how evolution could have happened billions of years ago, because they are artificial. Ribozyme "is entirely the product of 21st-century technology," and doesn't answer the question of how pre-biotic chemistry could give rise to the kind of reactions Joyce and Horning set up.

The experiments Carter and others did last year, he said, seem to point in a different direction, in which RNA molecules interacted with simple amino acids to act as a primitive kind of code for biochemistry.

Horning, though, likened the stage of their research to early nuclear experiments in physics. "For a while before they built a bomb, they understood that if you enrich uranium, you get generation of heat," he said. "Only after you had a critical mass, enough uranium together, could you get a process that was self-sustaining."

The next steps, he added, will be finding that combination of enzyme and RNA that sustains itself, and keeps reproducing.

No need to worry about creating life that will take over the world, Horning noted. RNA-based life was replaced by protein-based life precisely because protein-based life worked better. This is one reason why it's so hard to find evidence of what kind of RNAs existed billions of years ago. "[The] RNA world probably died out no less than 3 billion years ago," he said.

There are also implications for finding life elsewhere. While there's no real data on how often life happens in the universe as a whole, the research does point to the kind of chemistry that can get it started. "It begins to confirm something – that life doesn't need the genetic code."

The research appeared in the Aug. 15 issue of Proceedings of the National Academy of Sciences. 

Original article on Live Science.