How Did Life Get Started?

A 3-D structure of RNA.
Credit: SpaceDaily

The origin of life remains the deepest of enigmas: How did this supremely complex phenomenon get started? The explanation historically has revolved around DNA, the genetic molecule that serves as a pattern for building proteins. Proteins, in turn, form enzymes, which catalyze, or facilitate, biochemical reactions, including the construction of DNA.

And thus the paradox: Genes require enzymes, but enzymes require genes. Which came first?

After a long focus on DNA, many life scientists are coalescing around a concept called the RNA World, which postulates that life began with RNA, which, like DNA, is built of chains of molecules called nucleotides. Our understanding of RNA has come a long way since the 1960s, when the “central dogma” of molecular biology held that RNA was a simple messenger-boy that carried DNA’s information to ribosomes, the cellular factories where proteins get built.

Around 1980, biologists realized that not only could RNA transfer information, but, like proteins, it could also process chemicals – it could catalyze reactions. That ability to do both jobs suggested that RNA, not DNA, could be the primary molecule in life.

Portland State University Professor of Chemistry Niles Lehman.

DNA stores information “like a computer hard drive,” says Niles Lehman, professor of chemistry at Portland State University, “but beyond that, DNA doesn’t do anything. RNA, on the other hand, can fold into a 3-D structure, that also allows it to catalyze a chemical reaction.” (As Lehman indicates, to perform its catalytic function, an enzyme requires a specific three-dimensional shape.)

Still, even if RNA can catalyzes reactions, in modern cells it gets its information from DNA. So how could RNA have been assembled in a epoch before DNA existed? In a series of recent experiments, Lehman may have found an answer: Individual units, or “nucleotides,” of the RNA chain can “self-assemble” spontaneously.

Lehman and colleagues started their experiments by removing from a bacterium an RNA molecule that works as a self-replicating enzyme, cut it into four chunks, each about 50 nucleotides long, and then watched the chunks reassemble themselves into a working enzyme. “We mix the fragments together in salt water at 48 degrees, have lunch, and come back, and we have self-replicating RNAs in the test tube,” Lehman says.

Obviously, reassembling an enzyme you have stolen from a bacterium and then diced into pieces does not prove that a working enzyme could have formed in the prebiotic world, but there was a method to Lehman’s madness.

Fifty bases is something of a “magic number,” says Lehman, noting that chemist James Ferris of Renssalaer Polytechnic Institute has been able to string together 40 to 50 individual RNA nucleotides using clay as the catalyst. It’s conceivable that this could have happened in the prebiotic world as well.

Ferris said that Lehman’s self-assembly experiment answered a big unknown remaining from his study, which produced strings of RNA that were still too short to function as a catalyst. “One of the big questions is how we would get these longer RNAs that will be needed to catalyze reactions, and this sounds like an interesting possibility.”

Scientists speculate that, before life took hold, an “RNA World” existed on early Earth, in which elementary RNA formed and reproduced spontaneously.
Credit: NASA

If, as these experiments suggest, the RNA world begins with three steps (prebiotic synthesis of the individual RNA nucleotides, assembly of the intermediate chains, and then final assembly into longer chains) Ferris and Lehman have demonstrated steps two and three.. However Ferris notes that nobody has yet demonstrated a prebiotic synthesis for the individual nucleotide bases from which he constructed the RNA strands.

Still, Lehman says the new results suggest that RNA can achieve enough complexity to transition into the biological realm, especially since the RNA begins to replicate itself. At first, the RNA fragments join end to end, but the completed strands then begin to catalyze further assembly of RNA. This “autocatalysis” accelerates the reaction, but even more important, Lehman notes, “Forming more of itself is a critical essence of life.”

William Scott, an associate professor of chemistry and biochemistry who works on RNA at the University of California at Santa Cruz, commented that the self-assembly of fragments brings the RNA World one step closer to acceptance. “I think the idea that complex molecules can be assembled from RNA fragments instead of just RNA nucleotides is a very reasonable one.”

As the RNA World hypothesis becomes more plausible, RNA is gaining more respect. For one thing, it’s known to be ubiquitous, both as a temporary storehouse for information, and since 1980, as a catalyst. “The core of the ribosome, which makes proteins, is catalytic RNA,” says Lehman, “and all cells have ribosomes, so it’s absolutely fair to say that catalytic RNA is manifest in every single cell that we know.”

Lehman’s work was funded by a grant from NASA’s Exobiology and Evolutionary Biology program.