Move over DNA: Six new molecules can carry genes

All of a sudden, DNA has no reason to feel special. For decades it seemed that only a handful of molecules could store genetic information and pass it on. But now synthetic biologists have discovered that six others can pull off the same trick, and there may be many more to find.

The ability to copy information from one molecule to another is fundamental to all life. Organisms pass their genes to their descendants, often with small changes, and as a result life can evolve over the generations. Barring a few exceptions, all known organisms use DNA as the information carrier.

A host of alternative nucleic acids have been made in labs over the years, but no one has made them work like DNA.

This problem has now been cracked. "This unique ability of DNA and RNA to encode information can be implemented in other backbones," says Philipp Holliger of the MRC Laboratory of Molecular Biology in Cambridge, UK.

"Everyone thought we were limited to RNA and DNA," says John Sutherland of the MRC Laboratory of Molecular Biology in Cambridge, UK, who was not involved in the study. "This paper is a game-changer."

Evolving XNA

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.

A key hurdle 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.

They started with enzymes that do this in DNA only. Over the years the team made incremental tweaks until they produced enzymes that could work on XNAs.

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.

This is the first time artificial molecules have been made to pass genes on to their descendants. Because the XNAs can do this, they are capable of evolution.

"The immediate question is whether these XNAs can be introduced into cells," says Farren Isaacs of Yale University in New Haven, Connecticut. Once the XNAs were installed, they could replicate and evolve on their own. "That would be remarkable."

Journal reference: Science DOI: 10.1126/science.1217622

Origin of life

The finding is a proof of principle that life needn't be based on DNA and RNA. Astrobiologists have long suspected as much.
"This is very interesting with respect to the origin of life," says Jack Szostak of Harvard University in Boston, Massachusetts. Nowadays, all life-forms use either DNA or RNA to store genetic information. 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."