How did life evolve from nonlife? The jury's still out on that one, but scientists have now answered an equally important and related question: How did early RNA molecules grow longer and more complex without succumbing to destructive mutations? RNA, it turns out, can take a surprising amount of mutation and keep on ticking.
Scientists' best guess as to how life got kick-started in the primordial soup is that self-replicating RNA molecules acquired the ability to act like enzymes, using their shape to catalyze biochemical reactions essential for the growth of primitive cells. But therein lies a paradox: Larger genomes are required for higher complexity, yet the bigger the genome, the bigger the target for mutations that might turn it into gobbledygook. According to mathematical models, primitive RNA genomes, which lacked error-correcting enzymes, would have suffered a mutation overload long before they could have pulled off any tricks fancier than self-replication, let alone cell maintenance.
But these models have a weak link, according to a team led by Eörs Szathmáry, a mathematical biologist at the Institute for Advanced Study in Budapest, Hungary. The researchers focused on an assumption made by the models called the "error threshold," which predicts how big a genome can become before mutations warp its shape and render it useless.
To get a better handle on what the error threshold for early ribozymes might have been, the researchers turned to modern ribozymes. They pooled data on the effect of mutation on two simple ribozymes--one from yeast and another from viruses--that can cleave themselves in half. The team then tallied the effect of mutations on the ribozymes' shape and cleaving ability.
Ribozymes appear to be a whole lot tougher than was thought. Most single mutations did not affect the critical shape of the molecule, and multiple mutations tended to compensate for those that did. Based on their results, the researchers calculate that early ribozymes could have had as many as 100 simple genes, close to the minimum number thought to be required for primitive life. The team reports its results online this week in Nature Genetics.
This is "a landmark paper," says Günter von Kiedrowski, a biochemist at Ruhr University in Bochum, Germany. The next step, which von Kiedrowski calls "the big bang of biology," is to figure out how early self-replicating ribozymes came to be in the first place.