Hachimoji DNA

Sep 25, 2020
By Anastacia Wienecke

This DNA sequence is 4,395 “letters” (nucleotides) long and it gives the body the precise instructions it needs to construct collagen.

Before we jump into our discussion of hachimoji DNA, let’s talk a little bit about proteins.

Did you know that you are made up of proteins? Right this second, the proteins in your body are helping you digest food, send oxygen from your lungs to your muscles, and build tissues. Your body contains tens of thousands of unique types of proteins; the main difference between them has to do with their shape and function.

Believe it or not, if we focus on the 40% of your body mass that is not due to water, roughly half is protein. Use this simple equation to find out the mass of protein that’s in your body:

protein mass = 0.20 * total body mass

The most abundant protein in the human body is collagen. It gives structure to our skin, muscles, tendons, and bones. If you weigh around 150 pounds, then you probably have around 1021 (= 1,000,000,000,000,000,000,000) collagen proteins! Without them, we’d be human puddles. But… where do proteins like collagen come from?

It turns out that we make them!

Much like an instruction manual explains how to assemble a bookshelf, DNA lets the body know how to build each of the proteins that it needs. While the instruction manual uses various combinations of 26 letters to form words that convey information, DNA messages use various combinations of four molecules called nucleotides: adenine (A), thymine (T), guanine (G), and cytosine (C). 

Amazingly, synthesizing DNA is now commonly done in laboratories all over the world. One not-so-common recent foray however, involved synthesizing a strand of DNA with 8 different types of nucleotides. A team of scientists worked together and for the first time created a DNA helix with the usual suspects: A, T, C, and G in addition to the newcomers: P, Z, B, and S. Selecting these new nucleotides was tricky and it involved decades of trial and error. In the process, researchers learned that very few molecules have the correct chemical properties to serve as the “building blocks” of DNA. But, despite all odds, they eventually succeeded in creating a stable helical molecule. They named it “hachimoji” from the Japanese words for eight (“hachi”) and letter (“moji”).

 

 

Animation of hachimoji DNA. Each color represents a particular type of nucleotide. (Millie Georgiadis/Indiana University School of Medicine).

 

Now that we’ve successfully made DNA with 8 types of nucleotides, what can we use it for?

Data Storage

Rather than storing digital information in binary (the 0’s and 1’s computers use), we could store it in the 8 letters of hachimoji DNA. Let’s explore this a little. Each unit of binary information is called a “bit”. A 3-bit sequence can be represented by the following eight combinations of 0’s and 1’s:

000, 001, 010, 011, 100, 101, 110, 111

If we wanted to, we could assign each of these 3-bit sequences to a hachimoji nucleotide. This would look something like:

000 = A, 001 = T, 010 = C, 011 = G, 100 = P, 101 = Z, 110 = B, 111 = S

A binary sequence like this: 010000001, can be represented in hachimoji DNA like this: CAT. That’s three times fewer units of information (9 bits vs. 3 nucleotides).

In terms of data storage capacity, your 16Gb flash drive is equivalent to 48 billion nucleotides of DNA. Since a human nucleus contains 3 billion nucleotides, we would need just 16 nuclei to store 16GB. That is equal to about 64 hours of video, or 10,000 medium-resolution photos, or 4,000 songs at 3.5 minutes each. Regular DNA is half as efficient at data storage, so we would need 32 nuclei (see here for more details). 

Extraterrestrial Life

Any extraterrestrial life may very well use molecules as a way of saving genetic (or other) important information. With the successful synthesis of hachimoji DNA, we can begin to dissect the “how” behind this statement. Might information-storing molecules have a characteristic shape or behavior? More research should help us find out.

Other Endeavors

Currently, scientists are working to understand:

  • how to make new copies of hachimoji DNA in a living cell
  • whether hachimoji DNA has properties that could be useful in improving human health
  • how regular DNA became the genetic material of life
  • whether we can create DNA structures that contain 10 or 12 nucleotides

Exciting results await!

Di Lullo GA, Sweeney SM, Korkko J, Ala-Kokko L, San Antonio JD. Mapping the ligand-binding sites and disease-associated mutations on the most abundant protein in the human, type I collagen. J Biol Chem. 2002;277(6):4223-4231.

Hoshika S, Leal NA, Kim MJ, et al. Hachimoji DNA and RNA: A genetic system with eight building blocks. Science. 2019;363(6429):884-887.

Edited by Priya Hibshman and Yogitha Chareddy