Synthetic biologists have discovered that six other molecules can could store genetic information and pass it on. A host of alternative nucleic acids have been made in labs over the years, but no one has made them work like DNA. Until now, everyone thought we were limited to RNA and DNA. This is the first time artificial molecules have been made to pass genes on to their descendants. The finding is a proof of principle that life needn't be based on DNA and RNA.
Holliger's team focused on six XNAs (xeno-nucleic acids). DNA and RNA are made of a sugar, a phosphate and a base. The XNAs had different sugars, and in some of them the sugars are replaced with completely different molecules. Synthetic XNA, with its different sugar backbone to natural DNA, can mimic many of the properties of the real thing.
Holliger and his team engineered enzymes that helped the six types of XNA to assemble and replicate genetic messages. The enzymes transcribed DNA into the various XNAs, then back into new DNA strands — with 95% accuracy or more.
A major challenge for the team was to create enzymes that could copy a gene from a DNA molecule to an XNA molecule, and other enzymes that could copy it back into DNA. Once they had created these enzymes, they were able to store information in each of the XNAs, copy it to DNA, and copy it back into a new XNA. In effect, the first XNA passed its information on to the new one – albeit in a roundabout way. "The cycle we have is a bit like a retrovirus, which cycles between RNA and DNA," Holliger says. Because the XNAs can do this, they are capable of evolution.
Genetic transmission over successive DNA-to-XNA cycles allowed researchers to select for only those XNAs that attached to certain target proteins from a pool of random samples — a process akin to evolution over multiple generations.
“For the first time, this confirms that replication, heredity and evolution are possible in these alternative backbones,” says Holliger.."This is very interesting with respect to the origin of life," says Jack Szostak of Harvard University in Boston, Massachusetts. Many biologists suspect that the first life-forms used RNA, and DNA was adopted later. But we don't know why those two molecules were chosen: are they the best possible storage media, or were they simply the only things available?
Holliger suspects RNA was an opportunistic choice. "Clearly, there is no overwhelming functional imperative to use DNA and RNA," he says. Instead, life may have started with RNA simply because it was made in large quantities on the early Earth.
Most biologists think life on Earth began with RNA because it can both store information and catalyse useful reactions. In his latest experiment, Holliger has now shown that one of his XNA's – 1,5-anhydrohexitol nucleic acid, or HNA – can fold into a 3D shape and bind to specific target molecules. This is the first step in becoming an enzyme. The same thing had previously been done for threose nucleic acid (TNA).
This suggests XNAs might form the basis of life on other planets, where different environments led to different chemistry. "I would be surprised if we find truly extraterrestrial life that was based on DNA and RNA," Holliger says. "There might have been an XNA-world on a different planet."
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