Since the dawn of man, humans have long pondered not only if life existed on other planets, but also what that life would look like. For most people, this question conjures up images of green men with advanced technology. For most biologists who ask, “what do organisms that evolved on distant planets look like?,” they are pondering something much more otherworldly.
Biologists have hypothesized alien species may use different systems of genetic information. Every living organism on earth uses DNA with the same four nucleotides; cytosine, thymine, adenine, and guanine. Although this is common to all life as we know it, biologists have long speculated that these four nucleotides aren’t the only ones that could function. On Feb. 22, 2019, a paper about the creation of two new functioning nucleotides was published in Science Magazine. These two nucleotides expand our understanding of what alien genetic information may look like. This breakthrough could also impact the way we store large volumes of information.
The original article titled “Hachimoji DNA and RNA: A genetic system with eight building blocks” appeared in Vol 363, Issue 6429 of Science. Though hachimoji, from Japanese “Hachi” meaning eight and “Moji” meaning “Character”, contain 8 bases, only two of them are completely new. Two of the manmade bases, Z and P, were first synthesized back in 2015. The team Responsible for hachimoji DNA led by Shuichi Hoshika and Nichole A. Leal synthesized the new Purine analog dubbed “B” and the new pyrimidine analog “S”.
The first step in validating their research was to show that the bases Z, P, B, and S all have predictable thermodynamic properties. The predictability of thermodynamic properties of natural DNA is important for its stability. This allows a cell to be equipped to deal with changes in its DNA as a result of the environments that it lives in. The team found that the coefficient of correlation for the two properties they predicted where 0.89 and 0.87. The coefficient of correlation measures how closely two values are related, and implies two things are perfectly related if its value is one. These high values suggest that the thermodynamic properties of hachimoji DNA are sufficiently predictable.
Next, the new DNA was tested to see if it met Schrödinger’s requirements for a Darwin system. Schrödinger’s requirements are, regardless of the exact order of genetic bases the 3D structure is similar and predictable. This uniformity allows for the sequence of bases to code for different proteins, without changing shape to the point where the genetic material no longer behaves the same way. The results of these test found some difference in the bond angles. Acknowledging this, Hoshika and Lead’s team wrote that the differences in “hachimoji DNA fall well within the ranges observed for natural 4-letter DNA”. The similar variance of structure between the natural and synthetic DNA further supports the validity of Z, P, B, and S as alternative nucleotides.
The final step was to determine if hachimoji DNA could successfully be transcribed to a functioning RNA with a specific 3D shape, known as an aptamer. To test this the team recreated a DNA sequence found in spinach in hachimoji DNA. When the original DNA sequence is transcribed into RNA it fluoresces green under known conditions. It took Hoshika and Leal’s team several attempts to modify an RNA polymerase, a protein used to transcribe RNA from DNA, so it was capable of synthesizing hachimoji RNA. Not only was the aptamer successfully transcribed, but it also fluoresced the same way the spinach RNA aptamer did, which the team hoped to emulate.
The value of this breakthrough is not limited to the understanding of what organisms may look like on distant planets. It also may impact micro machines that use DNA for storage. With 4 base DNA, it is theorized that as much as 215 petabytes, 215 million gigabytes, of information can be stored in a single gram. As the number of bases increases, there is a corresponding increase in the amount of information that can be stored in the same volume of DNA. One of the benefits of using DNA for storage is that it has very high structural integrity over long periods of time, compared to modern silicon memory. Scientists have already used DNA to store short films with surprising success. The success of hachimoji DNA has increased our understanding of alternative genetic codes and may pave the way for future generations to use DNA suspensions for data storage.