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Synthetic XNA molecules can evolve and store genetic information, just like DNA

Out of all the possible molecules in the world, just two form the basis of life’s grand variety: DNA and RNA. They alone can store and pass on genetic information. Within their repetitive twists, these polymers encode the stuff of every whale, ant, flower, tree and bacterium.

But even though DNA and RNA play these roles exclusively, they’re not the only molecules that can. Vitor Pinheiro from the MRC Laboratory of Molecular Biology has developed six alternative polymers called XNAs that can also store genetic information and evolve through natural selection. None of them are found in nature. They are part of a dawning era of “synthetic genetics”, which expands the chemistry of life in new uncharted directions.

DNA looks like a twisting ladder. Its sides are chains of a sugar called deoxyribose (the D in DNA), connected by phosphate groups. Each sugar is attached to one of four ‘bases’ – these form the rungs of the ladder, and are signified by the letters A, C, G and T.

RNA is similar, with three important exceptions. It’s typically only half a ladder – a single helix, rather than DNA’s famous double. Its ‘T’ rung is a ‘U’. And its sugar is ribose rather than deoxyribose (hence, the R in RNA).

Both of these molecules are called nucleic acids. So are Pinheiro’s XNAs, but they make their ladders using different sugars. If arabinose stands in for deoxyribose, you get ANA instead of DNA. If cyclohexane plays the part, you get CeNA. If the role goes to threose, you get TNA, and so on. These differences aside, all the XNAs use the same bases and the same phosphate groups. Any of them could pair up with a complementary strand of DNA or RNA.

“They are very interesting with respect to the origin of life,” says Jack Szostak, a Harvard biologist who studies life’s beginnings and was not involved in the study. “In principle, many different polymers could serve the roles of RNA and DNA in living organisms. Why then does modern biology use only RNA and DNA?”

Most biologists now think that RNA preceded DNA as life’s chief information molecule. Phil Holliger, who led the new study, says that the “inescapable conclusion” is that its dominance was the result of a “frozen accident at the origin of life”. RNA may have gained supremacy because of random factors rather than some inherent quality, just as VHS and Blu-Rays eventually won out over Betmax and HD-DVDs.

The alternative is that some nucleic acids may be better at copying themselves, or speeding up other chemical reactions. “Phil’s work will certainly make it possible to compare the functional abilities of a wide range of synthetic nucleic acids,” says Szostak.

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