Saturday, August 25, 2012

DNA could have existed long before life itself

THE latest twist in the origin-of-life tale is double helical. Chemists are close to demonstrating that the building blocks of DNA can form spontaneously from chemicals thought to be present on the primordial Earth. If they succeed, their work would suggest that DNA could have predated the birth of lifeMovie Camera.

DNA is essential to almost all life on Earth, yet most biologists think that life began with RNA. Just like DNA, it stores genetic information. What's more, RNA can fold into complex shapes that can clamp onto other molecules and speed up chemical reactions, just like a protein, and it is structurally simpler than DNA, so might be easier to make.

After decades of trying, in 2009 researchers finally managed to generate RNA using chemicals that probably existed on the early Earth. Matthew Powner, now at University College London, and his colleagues synthesised two of the four nucleotides that make up RNA. Their achievement suggested that RNA may have formed spontaneously - powerful support for the idea that life began in an "RNA world".

Powner's latest work suggests that a rethink might be in order. He is trying to make DNA nucleotides through similar methods to those he used to make RNA nucleotides in 2009. And he's getting closer.

Nucleotides consist of a sugar attached to a phosphate and a nitrogen-containing base molecule - these bases are the familiar letters of the genetic code. DNA nucleotides, which link together to form DNA, are harder to make than RNA nucleotides, because DNA uses a different sugar that is tougher to work with.

Starting with a mix of chemicals, many of them thought to have been present on the early Earth, Powner has now created a sugar like that in DNA, linked to a molecule called AICA, which is similar to a base (Journal of the American Chemical Society, doi.org/h6q).

There is plenty still to do. Powner needs to turn AICA into a base, and add the phosphate. His molecule also has an unwanted sulphur atom, which helped the reactions along but now must be removed. Nevertheless, a DNA nucleotide is just a few years away, says Christopher Switzer of the University of California, Riverside. "It's practically a fait accompli at this point."

That could have important implications for our understanding of life's origins. Prebiotic chemists have so far largely ignored DNA, because its complexity suggests it cannot possibly form spontaneously. "Everybody and his brother has been saying 'RNA, RNA, RNA'," says Steven Benner of the Foundation for Applied Molecular Evolution in Gainesville, Florida.

Conventional wisdom is that RNA-based life eventually switched to DNA because DNA is better at storing information. In other words, RNA organisms made the first DNA.

If that is true, how did life make the switch? Modern organisms can convert RNA nucleotides into DNA nucleotides, but only using special enzymes that are costly to produce in terms of energy and materials. "You have to know that DNA does something good for you before you invent something like that," Switzer says.

He says the story makes more sense if DNA nucleotides were naturally present in the environment. Organisms could have taken up and used them, later developing the tools to make their own DNA once it became clear how advantageous the molecule was - and once natural supplies began to run low.

Early organisms must have scavenged for materials in this way, says Matthew Levy of the Albert Einstein College of Medicine in New York City. "The early Earth was probably a bloody mess," he says, with all manner of rich pickings on offer.

Powner suggests another alternative. Life may have begun with an "RNA and DNA world", in which the two types of nucleotides were intermingled. Powner's co-author Jack Szostak, of the Harvard Medical School, has shown that "mongrel" molecules containing a mix of DNA and RNA nucleotides can perform some of the functions of pure RNA (Proceedings of the National Academy of Sciences, doi.org/bj8r97). Powner suggests that life started out using these hybrid molecules, gradually purifying them into DNA and RNA.

Benner says it makes more sense for the first life to have used pure DNA and RNA as early as possible. Both work better than the mongrel molecules.

Right now, though, there's nothing to tell us exactly how and when life first used DNA. "It almost becomes a choose-your-own-adventure game," says Levy.

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