Today, cellular machinery coordinates a sophisticated process that involves proteins, DNA, and RNA all working in concert, with proteins typically serving as enzymes to catalyze reactions, and DNA and RNA storing and processing genetic information. If, as the RNA-world hypothesis states, RNA once was in the business of replicating RNA, then enzymes once were composed entirely of RNA and not amino acids the building blocks of protein. The first step then, in creating an RNA-world theme park, is to create RNA enzymes from scratch. To do this, Bartel employs a process developed with Harvard Medical School's Jack Szostak: in vitro evolution or evolution in a test tube.
Workers in Bartel's lab fill tubes with anywhere from 1 trillion to 1 quadrillion RNA molecules, selecting for those that can expand by forming chemical bonds with other RNAs. The molecules that can do this are isolated; the rest are discarded. These new, bigger RNAs are multiplied, returned to the tube and tested again for the same ability. Again, losers are removed, and winners multiplied. As this cycle repeats, slight mutations often appear in the RNAs, some of which create molecules superior to the parent molecule. Says Bartel, "Really, we end up selecting for the survival of the best molecules, and then propagating those survivors" Darwinian natural selection.
So far, Bartel's lab has demonstrated that these new RNA molecules can act as enzymes: In this case, they can bind to an RNA template molecule that serves as the pattern for producing, one nucleotide at a time, another RNA. The Science paper reported both good and cautionary news. The good news was that these RNA enzymes are flexible and robust enough to bind to just about any kind of template regardless of its sequence findings that eluded earlie
Contact: Kelli Whitlock or David Cameron
Whitehead Institute for Biomedical Research