From Pseudoscience to Frontier Science: Hachimoji DNA and the Exploration of Alien Genetic Codes

Written by aritra roy

Graduate student, Department of chemistry, ut austin

Image from Unsplash

An extraordinary scene unfolded at Mexico's Congress as two mummified 'alien' bodies were recently unveiled in a sealed glass case. Mexican journalist and self-proclaimed UFO enthusiast Jaime Maussan is the mastermind behind this extraterrestrial sensation. These curious beings are believed to have been found in Peru, near the Nazca Lines, in 2017. Maussan proudly presented his findings, claiming that about a third of their DNA is still an enigma. "These are not mummies," he said. "These are complete bodies that have not been manipulated." 

However, scientists aren't embracing the notion of extraterrestrial origins just yet. Julieta Fierro, a scientist from UNAM, has cast doubt on the claims, asserting that the presented results do not provide any substantial evidence for the existence of alien life. “He told me extraterrestrials do not talk to me like they talk to him because I don’t believe in them,” she added. Similarly, Elsa Tomasto-Cagigao, a Peruvian bio-anthropologist, questions the undue attention given to these far-fetched claims and wonders why they continue to dominate the spotlight. In contrast to the enthusiasm of some, the scientific community remains steadfast in its skepticism, maintaining that these alleged discoveries are, in all likelihood, hoaxes.

In the fascinating realm of biology, where we unravel the mysteries of life, one question has forever tickled our curiosity: what might extraterrestrial DNA look like? Would it mirror our genetic code, or could it be an entirely alien script from the cosmos? Surprisingly, there's no definitive answer to this question, and even the most imaginative speculations remain uncharted. Nonetheless, recent advancements in synthetic biology have initiated a new line of inquiry, igniting our interest in the potential for molecular evolution in genetic codes that vary significantly from our own. However, recent advances in synthetic biology have opened a new chapter of inquiry, sparking our fascination with the possibility of molecular evolution occurring in genetic codes that differ radically from our own. At the heart of life's intricacies lies the elegant structure of DNA  double helices. Envision these strands as the pieces of a complex puzzle, guided by the intricate architecture of DNA double helices and held together by hydrogen bonds–the vital glue sustaining life's harmony. 

When scientists kept these hydrogen bonds intact and introduced a third pair, these artificial DNA systems started behaving like natural DNA. They could be copied, amplified, sequenced, transformed into RNA, and switched back to DNA. They even got creative and added extra amino acids when making proteins. Do we stop at six? You guessed it right: why stop if we can have more? So, a group of researchers from Indiana University School of Medicine, the University of Chicago, and our very own, the University of Texas at Austin, crafted an "alien" genetic system with eight unique nucleobases in 2019. They called it “Hachimoji DNA.” In Japanese, hachi meaning "eight" and moji meaning "letters," and so, essentially, they've given life to an eight-letter genetic code. 

When we deal with regular DNA, we try to figure out how much energy it takes to form a double-stranded structure, and it's anything but straightforward. There's no single magic number for each base pair. Instead, it's a complex puzzle. Why? They're working with eight building blocks instead of the usual four! Think of it as adding extra gears to an already intricate machine. And to make things a tad more intriguing, they also had to consider symmetry. You can read about how they figured everything out here. Can you guess how many parameters they ended up handling? A whopping 40! That's 28 more than what's required for your regular DNA. It's like turning up the complexity dial to a whole new level. What's so exciting about it? Well, it packs more information into its DNA strands than the standard DNA we're used to. Plus, it keeps things predictably stable, no matter the sequence length. This opens up a world of possibilities, like using it for barcoding and combinatorial tagging, efficient information storage that's easy to retrieve, and even crafting self-assembling nanostructures. It's like having a supercharged Lego set for scientists! And here's the kicker: the differences in structure between various hachimoji DNA duplexes are no more significant than what we see in different regular DNA duplexes. This suggests that hachimoji DNA could potentially support molecular evolution. Think about it—this research takes us one step closer to understanding what kind of structures we might encounter as we explore the vast cosmos in search of life. It's the science that's actually out of this world!

Although making Hachimoji DNA using solid phase DNA synthesis has been well optimized and studied, our regular DNA sequencing machines can't read Hachimoji DNA sequences. So, researchers got creative and found smart ways to convert Hachimoji DNA into something those machines could understand. Nanopore sequencing is a technique that can detect unique DNA structures without the need for amplifying enzymes - DNA polymerases. This technology has shown promise in spotting different DNA modifications and complex nucleobase structures. Even more remarkable is what scientists found in 2023 at the University of Washington, Seattle. They discovered that Hachimoji DNA produces a broader range of signals during nanopore sequencing than regular DNA. This means we can sequence Hachimoji DNA with incredible accuracy and detail! This development paves the way for future designs of alternative DNA systems that can be seamlessly sequenced using existing molecular motors and pores. It's like fine-tuning the engine of a high-performance car for different types of terrain, ensuring a smoother ride in the world of genetics!

While these alien mummies may turn out to be nothing more than pseudoscience, the advancements in synthetic biology undeniably ignite our curiosity. They prompt us to ponder: could life exist beyond Earth, utilizing this distinctive set of eight genetic code letters for its own adaptation and evolution? Could we potentially encounter life forms akin to something out of science fiction, like real-life Teenage Mutant Ninja Turtles? Our curiosity knows no bounds as we continue with unwavering determination to explore the mysteries of the universe and the potential for diverse life forms to exist.