Aptamers were just the beginning. Unlike aptamers, which are capable only of sticking to something else, ribozymes can change the structure of other molecules. So Szostak then adapted the same process to evolving specialized ribozymes. Some can cut DNA apart, and others can put it back together. But of all the ribozymes that now exist, the ones that fascinate Szostak most are the ones that can do what his handmade RNAs couldn’t do: make new RNA.
SUGAR FIX Aided by borate, the core molecules from the cosmos react to form ribose, a five-carbon sugar that is a key ingredient of the genetic material ribonucleic acid (RNA). These molecules may also combine chemically to make four organic molecules known as adenine (A), cytosine (C), guanine (G), and uracil (U). These organic molecules, called nucleobases, make the genetic “alphabet” of the RNA. Long sequences of the four letters spell out the essential biological blueprint of every living organism. Szostak and many other scientists believe that self-replicating RNA, or something similar, may have served as the earliest genetic material and that DNA—the primary genetic material in all living things on Earth today—appeared only after millions of years of evolution. |
Today both Bartel and Szostak keep students and postdocs busy in their labs evolving improved ribozymes that can build longer copies. “What you really want is something that can go to 100 or 200 nucleotides and go completely every time,” says Szostak. That’s a big jump from what’s available today and perhaps the biggest one still left before anyone can claim to synthesize life. But it’s not much bigger than what has already been accomplished. “It’s getting really close,” says Szostak. “We don’t have to worry about whether it’s possible. We know it exists. Now we ask how we can tweak it to make it better or simpler.”
Szostak’s work with synthetic aptamers and ribozymes has convinced him that RNA could have once dominated the world. Meanwhile, other researchers have found evidence supporting the hypothesis in living cells. It turns out that RNA is far more versatile than scientists once thought. Last March, for example, biochemist Ronald Breaker at Yale University and his colleagues discovered that some RNAs self-destruct before they can be copied into a protein if they grab onto a certain molecule. Other RNAs, he found, work the other way: Only if they grab a certain molecule can they act as a template for a protein. These “riboswitches,” as Breaker calls them, are apparently essential to the workings of the cell. “The roles of RNA in the cell have expanded beyond what anyone imagined,” says Szostak. “Who knows what else is lurking in there?”
The best proof that life got its start as an RNA-based organism would be to create one. But for all the advances to date, there’s still plenty of work left to do before such a creature comes to life. A handful of ribozymes in a beaker—no matter how accomplished they may be—simply doesn’t make the cut. It’s as if Szostak wanted to prove that a car can exist; at this point, he’s got brake pads, a steering wheel, and a lot of other parts strewn across a yard. Now he’s got to get the pieces to work together.
The simplest way is to put the pieces in a container. All organisms alive today keep their DNA, RNA, and proteins together inside cell membranes. These oily bubbles prevent big molecules from getting out while letting smaller food molecules in. Today’s membranes are complex constructions, built by a carefully choreographed crew of enzymes. Their surfaces are studded with sophisticated channels that carefully regulate what goes in and out of the cell. And as the cell grows, the enzymes expand the membrane as well; when the cell divides, enzymes push apart the membrane and its contents into two new cells.
All this takes lots of genetic guidance. A simple organism with only a sliver of RNA couldn’t possibly build such a complicated container for itself. So four years ago, Szostak decided to expand his research on the RNA world: He set out to find a simple way to enclose his ribozymes.
The hunt for extraterrestrial life is heating up. In a decade, NASA hopes to launch a network of space-based telescopes that will be able to pinpoint Earth-like planets in other solar systems and see whether life has altered their atmosphere in the same way it has here on Earth—flooding it with oxygen, for example. Closer to home, scientists are designing devices that could be deployed on Mars or Europa, one of Jupiter’s moons, to detect microbial organisms. But it’s possible that even if extraterrestrial life exists, none of these searches will find it. That’s because everyone is trying to look for life in space that is like life on Earth. If life did emerge independently on some other planet or moon, it might be radically different, down to its very molecular basis. All living organisms on Earth use DNA, but there may be other molecules that can do the job as well. For several years now, scientists have been learning how to attach the four nucleotides of our genetic alphabet to new backbones. Two kinds of artificial molecules—known as PNA and TNA—have proven particularly promising. Astrobiologists are paying a lot of attention to Harvard biochemist Jack Szostak’s efforts to produce a self-replicating RNA molecule. If Szostak and his colleagues succeed, they will have created the first self-sustaining life that does not depend on DNA. Of course, RNA is not profoundly different from DNA (it’s a single-stranded variation). But a self-replicating RNA molecule would open the door to new ways of thinking about life elsewhere in the universe. —C. Z. |
