DNA gets a new - and bigger - genetic alphabet

Hachimoji DNA could be a far more durable way to store digital data that could last for centuries

In 1985, the chemist Steven A Benner sat down with some colleagues and a notebook and sketched out a way to expand the alphabet of DNA. He has been trying to make those sketches real ever since.
 
On Thursday, Benner and a team of scientists reported success: in a paper, published in Science, they said they have in effect doubled the genetic alphabet. Natural DNA is spelled out with four different letters known as bases — A, C, G and T. Benner and his colleagues have built DNA with eight bases — four natural, and four unnatural. They named their new system Hachimoji DNA (hachi is Japanese for eight, moji for letter).

 
Crafting the four new bases that don’t exist in nature was a chemical tour-de-force. They fit neatly into DNA’s double helix, and enzymes can read them as easily as natural bases, in order to make molecules. “We can do everything here that is necessary for life,” said Benner, now a distinguished fellow at the Foundation for Applied Molecular Evolution in Florida.
 

Hachimoji DNA could have many applications, including a far more durable way to store digital data that could last for centuries. “This could be huge that way,” said Nicholas V Hud, a biochemist at Georgia Institute of Technology who was not involved in research.

 
It also raises a profound question about the nature of life elsewhere in the universe, offering the possibility that the four-base DNA we are familiar with may not be the only chemistry that could support life.
 
The four natural bases of DNA are all anchored to molecular backbones. A pair of backbones can join into a double helix because their bases are attracted to each other. The bases form a bond with their hydrogen atoms.
 
But bases don’t stick together at random. C can only bond to G, and A can only bond to T. These strict rules help ensure that DNA strands don’t clump together into a jumble. No matter what sequence of bases are contained in natural DNA, it still keeps its shape.

 
But those four bases are not the only compounds that can attach to DNA’s backbone and link to another base — at least on paper. Benner and his colleagues thought up a dozen alternatives.
Working at the Swiss university ETH Zurich at the time, Benner tried to make some of those imaginary bases real.
 
“Of course, the first thing you discover is your design theory is not terribly good,” said Benner.
 
Once Benner and his colleagues combined real atoms, according to his designs, the artificial bases didn’t work as he had hoped.
 
Nevertheless, Benner’s initial forays impressed other chemists. “His work was a real inspiration for me,” said Floyd Romesberg, now of the Scripps Research Institute in San Diego. Reading about Benner’s early experiments, Romesberg decided to try to create his own bases.

 
Romesberg chose not to make bases that linked together with hydrogen bonds; instead, he fashioned a pair of oily compounds that repelled water. That chemistry brought his unnatural pair of bases together. “Oil doesn’t like to mix with water, but it does like to mix with oil,” said Romesberg.
 
In the years that followed, Romesberg and his colleagues fashioned enzymes that could copy DNA made from both natural bases and unnatural, oily ones. In 2014, the scientists engineered bacteria that could make new copies of these hybrid genes.
 
In recent years, Romesberg’s team has begun making unnatural proteins from these unnatural genes. He founded a company, Synthorx, to develop some of these as cancer drugs.

 
At the same time, Benner continued with his own experiments. He and his colleagues succeeded in creating one pair of new bases.

 
©2019 The New York Times News Service