By ANDY COGHLAN
Enzymes that don’t exist in nature have been made from genetic material that doesn’t exist in nature either, called XNA, or xeno nucleic acid.
It’s the first time this has been done and the results reinforce the possibility that life could evolve without DNA or RNA, the two self-replicating molecules considered indispensible for life on Earth.
“Our work with XNA shows that there’s no fundamental imperative for RNA and DNA to be prerequisites for life,” says Philipp Holliger of the Laboratory of Molecular Biology in Cambridge, UK, the same laboratory where the structure of DNA was discovered in 1953 by Francis Crick and James Watson.
It’s not all about the base
Holliger’s team has made XNAs before. Their unnatural XNA contains the same bases – adenine, thymine, guanine, cytosine and uracil – on which DNA and RNA rely for coding hereditary information. What’s different is the sugar to which each base is attached.
In DNA and RNA, the sugars are deoxyribose and ribose, respectively. Holliger made new types of genetic material by replacing these with different sugars or other molecules.
Now, they have taken a step closer to mimicking early life on the planet by showing that XNAs can also serve as enzymes – indispensible catalysts for speeding up chemical reactions vital for life.
One of the first steps towards life on Earth is thought to be the evolution of RNA into self-copying enzymes.
So by showing that XNAs can act as enzymes, on top of being able to store hereditary information, Holliger has recreated a second major step towards life.
The XNA enzymes can’t yet copy themselves but they can cut and paste RNA, just like natural enzymes do, and even paste together fragments of XNA.
It’s the first demonstration that, like prehistoric RNA, XNA can catalyse reactions on itself, even if it can’t yet copy itself as RNA can.
Holliger argues that RNA and DNA may have come to dominate Earth by chance, simply because they were the best evolutionary materials to hand. “You could speculate that on other planets, XNAs would dominate instead,” he says.
“This work is another nice step towards demonstrating the functional capabilities of XNAs,” says Nobel prizewinner Jack Szostak of Harvard University, who studies the origins of life on Earth .
“The possibility that life elsewhere, on exoplanets, could have started with something other than RNA or DNA is quite interesting, but the primordial biopolymer for any form of life must satisfy other constraints as well, such as being something that can be generated by prebiotic chemistry and replicated efficiently,” Szostak says. “Whether XNA can satisfy these constraints, as well as providing useful functions, remains an open question.”
Holliger says that XNAs may also have roles to play in medicine. Because they do not occur naturally, they can’t be broken down in the human body. And since they can be designed to break and destroy RNA, they could work as drugs for treating RNA viruses or disabling RNA messages that trigger cancers.
“We’ve made XNA enzymes that cut RNA at specific sites, so you could make therapies for cleaving viral or oncogenic messenger RNA,” says Holliger. “And because they can’t be degraded, they could give long-lasting protection.”
Journal reference: Nature, DOI: 10.1038/nature13982
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