Synthetic DNA 'evolves' with own enzymes

Scientists may have taken a significant step towards showing the existence of "alternative" materials as genetic materials.

 

Researchers replaced a standard part of the nucleic acids in DNA with chemical relatives and found they worked, tech site Ars Technica reported.

 

"Sequence information could be shuttled back and forth between these artificial molecules and DNA, and the synthetic materials could even undergo the sort of molecular evolution that has been demonstrated using DNA and RNA," Ars Technica said.

 

It said that while the chemical structure of nucleic acids is not too complex - a long polymer of sugars linked by a phosphate whose order conveys genetic information - they can be chemically "swapped out."

 

Phosphate can be replaced by a sulfate and the resulting molecule can still undergo base pairing with normal nucleic acids, it noted.

 

Also, other researchers have traded the sugar for related, ring-like structures.

 

"Some geneticists have even used relatives of the four standard bases that undergo base pairing that's structurally distinct. These synthetic molecules can actually be used by the normal cellular machinery if they're supplied to bacteria, creating an expanded genetic code," it said.

 

Replacing DNA

 

But messing with the sugars and phosphates may be harder since the enzymes that prepare and copy DNA are structured to work with sugars and phosphates, Ars Technica noted.

 

To work around this, the team fixed the enzymes, starting with a DNA copying enzyme, and random mutations.

 

It checked for versions that would latch on to a chemical that was somewhat structurally related to the normal sugar used in DNA.

 

The result was an enzyme that could copy stretches of DNA into pieces of a nucleic acid that contained nothing but this sugar substitute, converting the DNA into an artificial chemical relative.

 

With similar procedures, the same enzyme could be adapted to a wide variety of chemicals related to sugars.

 

"The authors picked five in total, all with features that were distinct from the normal sugars, like a double bond between carbon atoms, a fluorine replacing an oxygen, and a double-ring structure. Collectively, they termed these DNA/RNA substitutes XNAs," Ars Technica said.

 

Back to DNA

 

The researchers also made a second set of enzymes that can convert XNAs back to DNA.

 

But the process was more error-prone than one that relies on the typical enzymes that only work on DNA, introducing random mutations at frequencies between once every 4,000 bases to once every 500.

 

"Of course, random mutations are the raw material of evolution, so the authors decided to check out whether the XNAs could evolve new functions," it said.

 

The researchers made a collection of random strings of XNAs, and selected those that stuck to a couple of substances, such as a protein and an RNA.

 

Those that stuck were copied into DNA, amplified, and copied back to XNA, picking up mutations along the way. After a few rounds, they had sequences that stuck specifically.

 

While the different XNAs all look like sugars, mutated versions of various enzymes have been shown to be fairly flexible about what they work with in the past.

 

"(But for now at least), we don't have enzymes that can copy XNA into more XNA without going through DNA (although, reportedly, these are in the works). And the cell can't synthesize its own raw materials for XNA—they have to be supplied externally," it noted.

 

Still, it said it remains entirely possible to imagine thre could be XNA-based bacteria floating around a lab in the near future.

 

Carriers of genetic information

 

"In the meantime, the results tell us quite a bit, and could be useful," it said.

 

For starters, it said that while although DNA and RNA are effective carriers of genetic information and can combine that with biochemical activities, they're not the only molecules that can do so.

 

"Their role in life on Earth, then, may be a contingency. At the same time, this work suggests that life on Earth need not have started using the nucleic acids it uses now. It's entirely possible that some other related compound—one that was easier to generate from the raw materials on the early Earth—got life going, but was then replaced by RNA or DNA," it said.

 

It added this makes the job of origin-of-life researchers both easier as they do not have to limit their thinking to RNA and harder.

 

Also, it said options are wide open when it comes to life elsewhere.

 

On Earth, Ars Technica said there have been a number of attempts to produce nucleic-acid based therapies, and it has generally been found that skipping DNA and using some chemical relative is much more effective as the drugs last longer because the enzymes that normally break down loose DNA don't recognize the synthetic variant.

 

"The XNA-based system may allow us to produce these in huge quantities," it said. — RSJ, GMA News