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There may be other ways to build DNA and RNA Researchers have made a synthetic DNA that is made of eight bases instead of the normal four. This genetic system was capable of supporting the requirements of life. This work lays the foundation of how life could look on a different world.

One of the most fundamental building blocks of life on earth is DNA. This molecule consists of four base pairs and a negatively charged backbone that come together to form the double helix. If life existed elsewhere in the universe, would it use a different genetic information system?

Recent work done by Hoshika and his colleagues addresses this question. These researchers synthesized a type of DNA called “Hachimoji DNA,” which uses eight base pairs opposed to the original four. “Hachimoji” means “8 letters” in Japanese. Their work found that this new genetic system maintained the properties needed to support life. But what does that mean, exactly?

The “letters” in a DNA are four molecules called nitrogenous bases. These bases pair together to form the latter of the double helix. In natural DNA, A (adenine) binds with T (thymine) and G (guanine) binds with C (cytosine). The letter represents the name of the molecule. The synthesized Hachimoji DNA includes these bases plus four more synthetic bases. These new bases are labeled as P, B, Z, and S.

They chose these bases after many Hachimoji double helixes had been examined. They tested these molecules with varying combinations of synthetic and natural base pairs. After creating the DNA-like molecules, they ran experiments to see if they still maintained the properties needed to support life, such as an information containing molecule, molecule stability, and the ability to transfer genetic information.

The top row of molecules are the natural bases. The bottom row are the synthetic bases. Source: Wikimedia Commons.

To do this, they needed to determine if the Hachimoji DNA was an information containing molecule. This was tested by determining if the Hachimojio DNA could reproduce in expanded form. They did this by comparing the melting temperature and free energy of the Hachimoji and standard DNA molecules. Another fundamental property the researchers tested was molecule stability. If their 8-base molecule broke down under normal conditions, it wouldn’t make a very good carrier of genetic information. They did this by testing the stability of the molecule during mutations. 

Finally, the molecule needed to be able to transfer this genetic information to RNA, which is the temporary form our genes take that allows them to be expressed. First, the  researchers developed an enzyme to start the reaction. To test this, researchers used a fluorescent tag to track the RNA. This tag will bind to the RNA and cause it to glow.

The results of this work demonstrated that the Hachimoji DNA was stable. They also found that the molecule was able to maintain its shape regardless of mutations. The fluorescent tag showed that the Hachimoji DNA could be copied to the RNA-like molecule. 

This research shows that it is at least possible for DNA and RNA-like molecules to function with something other than 4 base pairs.. Thus, if it didn’t work exactly as it does on Earth, life may still be possible on other planets. This work has other implications beyond that of astrobiology. Due to the increase in bases, the Hachimoji DNA allows for greater storage of genetic information. The researchers believe that the Hachimoji DNA could have molecular applications. Some of these applications in species identification, drug development, and nanotechnology. This work could be an important tool for molecular biology and offer insight to the potential of life on other worlds.

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Study Information

Original study: Hachimoji DNA and RNA: A genetic system with eight building blocks

Study published on: Feb 22, 2019

Study author(s): Shuichi Hoshika, Nicole A. Leal, Myong-Jung Kim, Myong-Sang Kim, Nilesh B. Karalkar, Hyo-Joong Kim, Alison M. Bates, Norman E. Watkins Jr., Holly A. SantaLucia, Adam J. Meyer, Saurja DasGupta, Joseph A. Piccirilli, Andrew D. Ellington, John SantaLucia Jr., Millie M. Georgiadis, Steven A. Benner

The study was done at: Foundation for Applied Molecular Evolution (USA), Indiana University School of Medicine (USA), DNA Software Inc. (USA), University of Texas, Austin (USA), University of Chicago (USA)

The study was funded by: NASA, National Science Foundation, Templeton World Charity Foundation Inc., U.S. Department of Energy (DOE), National Institute of General Medical Sciences

Raw data availability: Supplementary Data: https://science.sciencemag.org/content/suppl/2019/02/20/363.6429.884.DC1

Featured image credit: Photo by Susan Holt Simpson on Unsplash