DNA is naturally composed of four basic molecules called nucleotides (commonly known as ‘letters’) — A (adenine), T (thymine), C (cytosine) and G (guanine) — that form hydrogen bonds in order to pair. A research team led by Dr. Steven Benner of the Foundation for Applied Molecular Evolution added an additional four synthetic nucleotides to produce an eight-letter genetic code and generate so-called hachimoji DNA (from the Japanese ‘hachi,’ meaning eight, and ‘moji,’ meaning letter). This new system, which is not a new life form, suggests astrobiologists looking for extraterrestrial life may need to rethink what they are looking for.
This illustration shows the structure of hachimoji DNA, which uses the four informational ingredients of regular DNA (green, red, blue, yellow) in addition to four new ones (cyan, pink, purple, orange). Image credit: Indiana University School of Medicine.
“Life detection is an increasingly important goal of NASA’s planetary science missions, and this new work will help us to develop effective instruments and experiments that will expand the scope of what we look for,” said Dr. Lori Glaze, acting director of NASA’s Planetary Science Division.
One way to imagine the kinds of foreign structures found on other worlds is to try to create something foreign on Earth.
Dr. Benner and his colleagues from the Foundation for Applied Molecular Evolution, Firebird Biomolecular Sciences LLC, the University of Texas, Austin, Indiana University Medical School, and DNA Software Inc. successfully achieved the fabrication of a new informational molecular system — hachimoji DNA.
The synthetic DNA includes the four nucleotides present in Earth life, but also four others that mimic the structures of the informational ingredients in regular DNA.
It can do everything that DNA does to support life. It pairs predictably, and rules predict its stability. It can be copied to make hachimoji RNA, able to direct protein synthesis.
Information storage, transmission, and selectable phenotype are three requirements of evolution. But there is a fourth: structural regularity.
“In 1942, Schrödinger predicted that no matter what genetic polymer life uses, its informational building blocks must all have the same shape and size. Hachimoji meets this prediction,” Dr. Benner said.
“Crystal structures of three different hachimoji DNA double helices reveal sequence-specific properties while retaining the essential features of natural DNA,” said co-author Dr. Millie Georgiadis, from the Indiana University School of Medicine.
“Careful analysis of the shape, size, and structural regularity in hachimoji DNA shows the importance of hydrogen bonding and charge in evolvable informational molecules,” said co-author John SantaLucia, from DNA Software Inc.
But could hachimoji DNA have arisen on other planets?
“We do not suggest that this eight-letter alphabet arose prebiotically, any more than we think that DNA-RNA-protein arose together. However, we can imagine parallel processes,” said co-author Dr. Andrew Ellington, from the University of Texas, Austin,
On Earth, life struggled first to improve RNA, modifying its building blocks. Some of these modifications survive today. However, terran biology eventually took a different route, inventing proteins.
On another planet, life may have continued to improve its RNA without inventing proteins, maybe to give an eight-letter system that this work shows is possible.
“However, it is wrong to say that hachimoji DNA is alien life,” Dr. Benner said.
“For that, the system also must be self-sustaining.”
Hachimoji DNA requires a steady supply of lab-created building blocks and proteins from an attentive scientist. As none of these are available outside, hachimoji DNA can go nowhere if it escapes the laboratory.
It also has many applications. These include improved diagnostics, alternatives to silicon for information storage, proteins with extra amino acids, and new kinds of drugs.
“Parts of this new DNA are already in products to diagnose disease and monitor the environment for disease-causing viruses,” said Mark Poritz, from Firebird Biomolecular Sciences LLC.
“It is exciting whenever basic science can impact people’s health, as this work can.”
“This study reminds us of how much we have yet to learn about DNA and RNA,” said Dr. Jack Szostak, 2009 Nobel Laureate in Medicine, whose own research concerns RNA and the origin of life.
“That learning comes by studying hachimoji DNA.”
The research is published in the journal Science.
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Shuichi Hoshika et al. 2019. Hachimoji DNA and RNA: A genetic system with eight building blocks. Science 363 (6429): 884-887; doi: 10.1126/science.aat0971
