Move over DNA! Synthetic genetic molecules discovered

Matt Bradley reports on the news that synthetic biologists have discovered six other  molecules that can store and pass on genetic information, just like DNA

DNA and RNA have long been thought of as the bricks and mortar of life, but scientists have now discovered that they are perhaps not the only building materials from which life can be constructed.

In a new study, published in Science, a team led by Philipp Holliger of the UK Medical Research Council’s Molecular Biology Lab, created six artificial DNA and RNA analogues that were able not only to carry genetic information, but also to replicate two of the most important capacities of their natural counterparts: heredity and evolution.

The xeno nucleic acids, or XNAs, were created by replacing the sugars that make up the backbone of normal DNA and RNA with six other compounds, some of which were merely different sugars, and some of which were completely different molecules.

This left the genetic information encoded in the nucleobases intact, but replaced the deoxyribose and ribose chains that make up the double and single helix structures in DNA and RNA.

Artificial DNA-like polymers are nothing new; much research has been done into replacing both the bases and the sugars in DNA and RNA. However, the study by Holliger and his team was more interested in a further question: whether synthetic polymers can interact with, and perform some of the same jobs as those found in nature.

In order to perform these functions, researchers first developed a series of enzymes that could copy information from a standard DNA molecule into the XNA, and then back into DNA. Then, they modified the enzymes so that they were able to act on the XNA molecules, copying their information into DNA and then back into XNA.

The XNAs were effectively able to pass on their information to new XNA molecules, though the need for a DNA intermediary means that it is not quite a fully synthetic process.

This represents a breakthrough for synthetic biology, as the ability to pass on information from one generation to the next allows for the possibility of evolution.  Dr Holliger and his researchers were able to create evolutionary pressure, by designing one of the XNAs to bind to a particular protein, and washing away those that failed. Those that succeeded, passed on their genetic information, along with some introduced mutations, allowing the XNAs to become better at binding more tightly to the protein.

“We’ve been able to show that both heredity – information storage and propagation – and evolution, which are really two hallmarks of life, can be reproduced and implemented in alternative polymers other than DNA and RNA,” Dr Holliger said.

The next step is to try to develop a way for XNAs to replicate themselves without the intervention of traditional DNA as an intermediary step.

The work has implications for a diverse range of fields. First and foremost, it brings synthetic biology a significant step closer to being able to create entirely new forms of life with a different chemistry. However, researchers have urged caution to make sure that artificial biological material does not damage our ecology – XNAs are not biodegradable.

This danger may also provide another avenue for development. In being resistant to natural enzymes that degrade natural DNA and RNA, XNAs may have applications in biotechnology and therapeutics. While DNA and RNA tend to become damaged fairly quickly in the presence of many natural biological materials and enzymes, XNAs, by being able to operate in environments that would harm other molecules, may be able to perform tasks that the former cannot.

The work also provides an insight for exobiologists (those who research extraterrestrial biology) into how life on other planets might work.

By demonstrating that there is no overriding functional reason for DNA and RNA to dominate, it allows for the possibility that other planets with different chemical constitutions to our own may give rise to life with completely different biologies. As Dr Holliger notes, “There is nothing ‘Goldilocks’ about DNA and RNA – there is no overwhelming functional imperative for genetic systems or biology to be based on them.”

There are also implications for research into the origin of DNA and RNA themselves. While Holliger doesn’t believe that XNAs were involved in the early development of life, by showing that RNA and DNA are not the only molecules that can perform their information carrying and evolutionary functions, his research could pave the way for a better understanding of the information carrying molecules that preceded them.

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