Evolution in a Test Tube
David Bartel’s career as a biochemist began marked by tension between his exceedingly meticulous method and the most careless of biological processes. Evolution, the process in which living things change and diversify from their predecessors, is random, at moments appears illogical, and leads to many dead ends. But in a seminal paper published in 1993, with clear thought and clever technique Bartel, along with thesis advisor Jack Szostak, brilliantly distilled the highly complex nature of evolution literally into a test tube.
Bartel focused on “ribozymes,” a class of molecules composed entirely of ribonucleic acid (RNA) that catalyze chemical reactions. Starting from a synthetic large pool of different RNA molecules of random sequence, he used a technique called in vitro selection to isolate a new type of ribozyme that performed a specific chemical reaction, known as an RNA ligation, otherwise only attributed to natural protein based enzymes. He then evolved these ribozymes by introducing random mutations into their sequence and re-isolating more active versions that outcompeted earlier variants—in effect modeling evolution in a test tube.
Naturally occurring ribozymes are rare—a host of enzymatic activities they may have once possessed have been appropriated to faster and more accurate proteins during evolution—but owing to their structural similarity to DNA, and catalytic potential, they are attractive candidates for the original self-replicating macromolecules, predating more complex life forms.
While generation of a self-replicating ribozyme remains elusive, and would not prove that catalytic RNAs directly preceded life, Bartel’s study was paramount in demonstrating the ability to isolate ribozymes with new activities. He notes, “We’re left with lots of gaps in knowing how RNA based life forms might have emerged, but it is still useful to know what RNA can do.”
Appreciating the highly mutable nature of evolution, Bartel also recognizes that the particular ribozyme he isolated was only one possible outcome of the experiment. “Evolution is the sum of a huge number of chance events, and the biological world is the culmination of all these chance happenings,” says Bartel. “If you replayed a tape of biological evolution, we would all look different.”