By David N. Leff

¿Mommy, where did I come from?¿ a 9-year-old boy asks his mother. ¿Let your father tell you,¿ she answers.

So the kid¿s dad sits him down and goes through the standard sex-education protocol for small children ¿ starting with the birds and bees, then on to sperm, eggs and intercourse. ¿Now, do you understand?¿ his parent asks.

¿Not really, Dad,¿ the bewildered child replies. ¿My friend Tommy told me he came from Chicago, and I was wondering where I came from.¿

We bewildered grown-ups have been wondering for ages where humans, and all living creatures, came from. One long-favored answer was Adam and Eve.

A more modern big-bang origin-of-life scenario, realizing that life needs enzymes, made out of proteins, and genes, made out of DNA, gave rise to the idea that RNA ¿ ribonucleic acid ¿ might have been doing both. This ushered in the ¿RNA World¿ hypothesis, which is purported by some to have jump-started life on Earth.

¿We will never be able to prove the existence of the RNA World,¿ observed biologist and biochemist David Bartel,¿ because we can¿t go back in time, but we can examine the basic properties of RNA and see if these are compatible with the RNA World scenario.¿

Bartel, an investigator at the Whitehead Institute in Cambridge, Mass., and an associate professor at Massachusetts Institute of Technology, is senior author of a paper in the current issue of Science, dated May 18, 2001. Its title:¿ RNA-catalyzed RNA polymerization: Accurate and general RNA-templated primer extension.¿

¿What we showed in that paper,¿ Bartel told BioWorld Today, ¿is that we could create an enzyme made of RNA, which can catalyze a type of polymerization reaction that would have been needed early in evolution to replicate RNA in an RNA World.¿

A New (RNA) World Is Born

The concept of such a world, he recalled, surfaced twice in the last decades of the 20th century. Until then, researchers thought that RNA was nothing more than a molecular interpreter that helped translate DNA codes into proteins. ¿The idea of the RNA World actually arose in the late 1960s,¿ Bartel recalled, ¿as people were looking at the shapes that RNA might be able to form. Some thought that maybe RNA came before proteins to catalyze reactions needed for early life forms. Then in the 1980s,¿ he continued, ¿the idea gained a lot more popularity, when it was first found that not all of the enzymes in biology are made out of protein. Some are made of RNA.

¿People have been looking into it ever since,¿ he went on,¿ but there are big problems with the RNA World hypothesis. The other important event that¿s happened is that the peptidyl transferase center of the ribosome ¿ the part that joins the amino acids together ¿ turned out to be RNA, not protein. That was big news last year.

¿So what we have at present,¿ Bartel went on, ¿is this very compelling evidence that even in the production of protein today, RNA has a very central role. So you get the idea,¿ he pointed out, ¿that right at the center of protein production is RNA. This really supports the notion that early RNA figured out how to make proteins. That helps us think how proteins came about. RNA came before proteins. Then the issue is: Could RNAs have done other types of reactions needed early in evolution?

¿The scientists looking at this are just now asking that question. We¿re asking it, but we¿re not particularly advocating one idea or the other. We¿re just addressing this question of whether there are some RNA sequences that can do this. I wouldn¿t think about it so much as a debate between pro and con RNA World factions. Even the scientists espousing that concept see its problems.

¿The problems come with where the RNA would come from,¿ Bartel explained. ¿What it would take for the prebiotic synthesis of RNA ¿ 4 billion years ago, before you had any enzymes ¿ is a very troubling question. Even if RNA came before proteins, most people doubt that life would have originated with RNA, but with something else. And that, of course, is very unsatisfying.

¿On the other hand, given the state of our knowledge of prebiotic chemistry, one could make a case that life would never have originated at all ¿ ever. We have evidence to the contrary. But you can¿t validate or confirm the RNA World hypothesis. There¿s nothing you can do to show that it existed. What you can do is look at the fundamental properties of RNA and see if they¿re compatible with the RNA World concept. So those are the things that we do.¿

From Scratch ¿ A Prototype RNA Enzyme

What he and his co-authors did, starting from scratch in the lab, and employing combinatorial chemistry, was create an RNA catalyst ¿ a ribozyme ¿ possessing some of the key properties needed to sustain life in an RNA World. It suggests that RNA could have had the ability to replicate itself and sustain life in early evolution, before the advent of DNA and proteins.

The ribosome they generated can use information from a template RNA sequence to make a third, new RNA ¿ with more than 95 percent accuracy. It can extend this new strand adding up to 14 nucleotides, to make more than one complete turn of the RNA helix.

¿Our next step,¿ Bartel said, ¿would be to try to make the efficiency of this enzyme much greater. Right now the reason that it doesn¿t go much more than one turn of the helix is that it just isn¿t efficient enough, not fast enough. So we really need to improve the speed. The goal here is to get an enzyme that can do this polymerization reaction so efficiently and accurately that it can replicate itself.¿

Why do NIH grants support Bartel¿s project? His reply: ¿NIH is interested in the fundamental science of biomolecules, and also sees spin-offs, such as the ability to make new enzymes, from the technology that we are developing. Some other things that we do with our RNA World project,¿ he added, ¿are funded by NASA. It¿s interest is in extraterrestrial life,¿ he concluded, ¿so they would like to know what stages life might have gone through on Earth during early evolution.¿

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