synthetic genetic evolution...,

TheScientist | Synthetic genetic polymers, broadly referred to as XNAs, can replicate and evolve just like their naturally occurring counterparts, DNA and RNA, according to a new study published today (April 19) in Science. The results of the research have implications not only for the fields of biotechnology and drug design, but also for research into the origins of life—on this planet and beyond.

“It’s a breakthrough,” said Gerald Joyce of The Scripps Research Institute in La Jolla, California, who was not involved in the study—“a beautiful paper in the realm of synthetic biology.”

“It shows that you don’t have to stick with the ribose and deoxyribose backbones of RNA and DNA in order to have transmittable, heritable, and evolvable information,” added Eric Kool of Stanford University, California, who also did not participate in the research.

Over the years, scientists have created a range of XNAs, in which the ribose or deoxyribose portions of RNA and DNA are replaced with alternative molecules. For example, threose is used to make TNA, and anhydrohexitol is used to make HNA. These polymers, which do not exist naturally, are generally studied with various biotechnological and therapeutic aims in mind. But some researchers, like Philipp Holliger of the MRC Laboratory of Molecular Biology in Cambridge, UK, think XNAs might also provide insights into the origins of life. They might help to answer questions such as, “why is life based on DNA and RNA, and, if we ever find life beyond earth, is it likely to be based on the same molecule or could there be other possibilities?” Holliger said.

To get at some of these questions, Holliger and his colleagues had to first create enzymes that could replicate XNAs, a necessary first step to evolution. They did this both by randomly mutating and screening existing DNA polymerases for their ability to read XNA, and by an iterative process of selecting polymerase variants with capacities for XNA synthesis. In the end, they had several polymerases that could synthesize six different types of XNA.

To see whether XNAs could evolve, they generated random HNA sequences, then selected for those that could bind to two target molecules. After selection, the HNAs were amplified by the newly designed polymerases and again selected for their ability to bind the targets. Eight rounds of selection later, the HNA sequences were no longer random, as those with a particular target-binding motif became more abundant. Through selection and replication, the HNAs had evolved.

The finding in itself is not surprising, said Kool. “Chemists have been working for 20 years to find new backbones for DNA and the feeling always was that it would be interesting and quite possible that some of them might be replicated one day.” It was, nevertheless, impressive, he added. “The hard part was finding the enzymes that could do it. So the big leap ahead for this paper was finding those enzymes.”