Scientists Successfully Double the DNA Alphabet

“Hachimoji DNA” is structurally sound, offers new possibilities for data storage and raises questions about the molecular makeup potential alien life

hachimoji animation
An animation of the eight color-coded bases of hachimoji DNA Millie Georgiadis/Indiana University School of Medicine

In 1953, when scientists conclusively identified DNA’s structure, it was a monumental, Nobel-Prize-winning revelation: four nucleotides, each containing a letter-labeled base, were arranged in a double helix structure. These four bases, or “letters,” form pairs: adenine, A, matches with thymine, T, and cytosine, C, bonds with guanine, G. These pairs are essentially the building blocks of life on Earth; the way in which the pairs are arranged creates the genetic instructions for how proteins are made, which in turn aid in pretty much every critical process that keeps us alive.

Now, an interdisciplinary team of researchers has expanded the genetic alphabet by creating synthetic DNA that uses eight letters rather than four, according to a new study published in the journal Science. The new manufactured structure is called "hachimoji DNA," from the Japanese words for "eight" and letter." Creating hachimoji DNA was, as Carl Zimmer writes in The New York Times, “a chemical tour-de-force” for the group led by Steven Benner, a synthetic biologist at the Foundation for Applied Molecular Evolution. The advance offers new possibilities in many fields, including medical research and data storage.

Synthetic DNA is made from scratch in a laboratory. The custom-programmed DNA can provide instructions that might not occur in nature. Right now, synthetic DNA—using the typical four bases—has been engineered for novel purposes, like creating new scents for perfume, but there are also potential medical applications, like manufacturing an enzyme that can break down gluten and treat celiac disease.

“Hachimoji DNA” adds two new pairs—P and Z, then B and S—into the mix. Previous work has created different versions of six-base synthetic DNA structures. Eight-base DNA dramatically expands the possible number of three-letter combinations, or codons, that DNA can store.

Wired’s Megan Molteni explains:

“A four-letter alphabet gives you 64 possible codons, which yield 20 amino acids, the building blocks of proteins. Six letters takes you up to 256 codons; eight makes it 4,096.”

Most previous attempts at adding base pairs were unstable because they used water-repelling molecules at their bases, reports Matthew Warren for Nature. New synthetic pairs could be squeezed in between natural pairs, but couldn’t be placed in a row. The hachimoji DNA, however, uses hydrogen bonds—just like naturally-occurring DNA—adding structural integrity.

In nature, DNA contains the instructions to build proteins. A key step in that process is creating a mirror-image strand of RNA. Otherwise, the information stored in DNA remains unused, like a recipe that’s never cooked. You won’t be able to observe the effect of any newly created genes, let alone see evolution. Study co-author Andrew Ellington, an evolutionary engineer at the University of Texas, synthesized an enzyme that could read the hachimoji DNA (including the new letters) and make a corresponding RNA strand. The RNA worked as designed, Wired’s Megan Molteni reports: some created a green fluorescent glow, while others bound to liver tumors or breast cancer cells in a petri dish.

Hachimoji DNA’s upgraded storage capacity means that we could use the eight-letter DNA to store information, like a super-durable, microscopic computer chip. As Ed Yong explains in National Geographic, researchers can create a key that translates information from the language of computers—binary 1’s and 0’s—into the letters of the DNA alphabet. DNA lasts far longer and takes up much less space than hard drives, and researchers have successfully stored a full computer operating system and an entire movie in normal, four-letter DNA.

The discovery also helps answer a biological quandary: could life exist using other building blocks other than the four nucleotide bases that are used on this planet? Synthetic biologist Floyd Romesberg told Nature that the new research is “a conceptual breakthrough.”

“For a long time, we had hints that life evolved from G, A, T, C, not because they were exactly the right raw materials but because they were simply available,” Romesberg said in an interview with Wired, and this study is the first to confirm that suspicion.

NASA, one of the organizations that funded the study, announced in a press release that the hachimoji DNA research will inform its search for life on other planets, since the discovery suggests that extraterrestrial life might not use the same building blocks as life on Earth.

But have the scientists created a whole new type of life on Earth? No, according to Discover. While hachimoji DNA meets all the structural requirements for life, it can’t sustain itself outside of the carefully calibrated lab environment.

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