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Was simple TNA the first nucleic acid on Earth to carry a genetic code?

YOU鈥橵E heard of DNA and RNA, but what about TNA? It resembles its more famous cousins in almost every respect, except that it is based on a sugar called threose instead of the deoxyribose found in DNA and the ribose in RNA.

Researchers have speculated that because threose is a simpler sugar than ribose, TNA could be a long-lost precursor to RNA. 鈥淚f nature was challenged to make threose or ribose, threose is easier to make,鈥 says Albert Eschenmoser, whose team at the Swiss Federal Institute of Technology in Zurich first made TNA three years ago by painstaking chemical synthesis.

Now Jack Szostak, a molecular biologist at Massachusetts General Hospital in Boston, has shown that TNA can be assembled by natural enzymes. He and John Chaput started with a single strand of DNA and added the nucleotide building blocks needed to make the complementary strand. But instead of the usual nucleotides, they added ones containing threose instead of deoxyribose. Despite the slightly different chemistry, the DNA polymerase enzyme slotted the threose-based nucleotides into place to form a DNA-TNA hybrid molecule (Journal of the American Chemical Society, DOI: 10.1021/ja035917n).

鈥淭he amazing thing about TNA is that even though the sugar-phosphate backbone is one carbon atom shorter than in RNA or DNA, it still shows excellent base-pairing properties,鈥 says Szostak. He plans to find out more about TNA鈥檚 properties, such as whether it can catalyse chemical reactions like RNA can. That would support the idea that TNA preceded RNA, though this may be impossible to prove. But researchers could at least explore whether TNA-based biology is feasible. 鈥淪zostak could evolve a TNA world,鈥 Eschenmoser says.

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