Synthetic molecules resembling DNA can function and evolve just like the real thing, its developers say.
These new, unnatural building blocks could be more useful than DNA or its closely related biomolecule, RNA, in a variety of medical and biotechnology applications, researchers added. Other investigators noted they could even lead to novel forms of life.
DNA is essentially made of four different kinds of molecules known as nucleic acids, commonly referred to by their initials, A, G, C and T. These run along a backbone made of sugars and phosphate groups.
Scientists call their artificial nucleic-acidlike molecules XNA, in which the natural sugar component has been replaced by one of six alternative organic compounds. These XNA molecules all can bind to DNA and RNA.
The researchers also have developed enzymes that can synthesize XNA from a DNA template, plus others that can "reverse transcribe" XNA back into DNA. This means they can store and copy data just as DNA can — the basis of heredity for all life on Earth.
The investigators subjected an XNA molecule to artificial natural selection in the lab by introducing mutations into its genetic code. By allowing the different versions of the molecule to compete against each other for binding to another molecule, the team ended up with a shape that bound tightly and specifically to the target – just as one would expect of DNA under the same conditions. This makes XNA the only known molecules other than DNA and RNA capable of Darwinian evolution.
"Heredity — information storage and propagation — and evolution, two of the hallmarks of life, can be implemented in polymers other than DNA and RNA," researcher Philipp Holliger at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England, told InnovationNewsDaily.
One notable property of XNA molecules is they are not biodegradable: They are impervious to natural enzymes that degrade DNA and RNA. As such, they could find use in medical and biotechnology arenas where DNA and RNA could not go.
"People use RNA and DNA for biotechnology, therapeutics, diagnostics and biosensing applications, but these are very fragile in the face of biology — they degrade very rapidly if there's any contact with biological materials," said biochemist Gerald Joyce at the Scripps Research Institute, who did not take part in this work. "As such, chemists have to work to make them resistant to natural enzymes that degrade RNA and DNA, and then you have to worry about losing the good properties of those molecules. These XNAs, however, are resistant from the get-go."
These findings might also shed light on the origins of life — specifically, why DNA and RNA came to dominate Earth.
"It shows that there is no overwhelming functional imperative for life to use DNA and RNA for genetic information storage and propagation. More likely, this choice reflects a 'frozen accident' from the origin of life," Holliger suggested.
The construction of genetic systems based on alternative chemical platforms may ultimately lead to the synthesis of novel forms of life, if researchers can devise a system for XNA to replicate itself just as DNA has, Joyce said. However, he cautioned that synthetic biologists should take care to "not tread into areas that have the potential to harm our biology." For instance, the fact that XNA is not biodegradable suggests that life might not have any easy way of breaking it down.
"Do I think what these researchers have done is dangerous? Absolutely not. Do I think this is going to be dangerous in the near or even medium term? Absolutely not," Joyce said. "Still, are we treading into something risky here? It's synthetic biology, not a natural form of biology. Scientists have to pay attention here."
The scientists detailed their findings in the April 20 issue of the journal Science.
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