Monday, February 25, 2019

Four New DNA Letters Double Life’s Alphabet

The DNA of life on Earth naturally stores its information in just four key chemicals — guanine, cytosine, adenine and thymine, commonly referred to as G, C, A and T, respectively.

Now scientists have doubled this number of life’s building blocks, creating for the first time a synthetic, eight-letter genetic language that seems to store and transcribe information just like natural DNA.

In a study published on 22 February in Science, a consortium of researchers led by Steven Benner, founder of the Foundation for Applied Molecular Evolution in Alachua, Florida, suggests that an expanded genetic alphabet could, in theory, also support life.

“It’s a real landmark,” says Floyd Romesberg, a chemical biologist at the Scripps Research Institute in La Jolla, California. The study implies that there is nothing particularly “magic” or special about those four chemicals that evolved on Earth, says Romesberg. “That’s a conceptual breakthrough,” he adds.

Normally, as a pair of DNA strands twist around each other in a double helix, the chemicals on each strand pair up: A bonds to T, and C bonds with G.

For a long time, scientists have tried to add more pairs of these chemicals, also known as bases, to this genetic code. For example, Benner first created ‘unnatural’ bases in the 1980s. Other groups have followed, with Romesberg’s lab making headlines in 2014 after inserting a pair of unnatural bases into a living cell.

But the latest study is the first to systematically demonstrate that the complementary unnatural bases recognise and bind to each other, and that the double helix that they form holds its structure.

Benner’s team, which includes researchers from various US companies and institutions, created the synthetic letters by tweaking the molecular structure of the regular bases. The letters of DNA pair up because they form hydrogen bonds: each contains hydrogen atoms, which are attracted to nitrogen or oxygen atoms in their partner. Benner explains that it’s a bit like Lego bricks that snap together when the holes and prongs line up.

By adjusting these holes and prongs, the team has come up with several new pairs of bases, including a pair named S and B, and another called P and Z. In the latest paper, they describe how they combine these four synthetic bases with the natural ones. The researchers call the resulting eight-letter language ‘hachimoji’ after the Japanese words for ‘eight’ and ‘letter’. The additional bases are each similar in shape to one of the natural four, but have variations in their bonding patterns.

The researchers then conducted a series of experiments that showed that their synthetic sequences shares properties with natural DNA that are essential for supporting life.

by Matthew Warren, Nature |  Read more:
Image: Science Source/Science Photo Library