DNA of life on Earth has been made up of only four letters: G, T, C, and A, which together form the code underlying every living entity on the planet. But that’s until now, since scientists have announced the development of the first semi-synthetic organism using an expanded genetic code.
Synthesizing a DNA base pair in their 2014 study, the researchers created bacteria that thrive using the expanded “genetic alphabet.” With an additional X and Y for an “unnatural base pair” (UBP), the modified E. coli bacterium maintains a genetic code of six letters.
“We’ve made this semisynthetic organism more life-like,” said lead researcher and The Scripps Research Institute professor Floyd Romesberg in a statement, with the hope that the groundbreaking work could lead to bugs that can help produce new drugs in the future.
Building A New Organism
Previously, a UBP could be incorporated into the E. coli’s DNA, but the resulting organisms grew slowly and the UBP was wiped out after rounds of cell division. Now, the team demonstrated that their organism can hold on well to the artificial base pair even as it divides.
This stability is deemed important for the organism’s survival, as one’s genetic information need to stay put during one’s lifetime.
“Your genome isn’t just stable for a day,” Romesberg added.
To do this, the researchers modified what’s known as a nucleotide transporter, which helps the bacteria import the UBP. Used in 2014, the transporter made the organism “very sick,” so the current modification addressed that problem.
Next, they optimized the previous version of Y, now better recognized by the enzymes synthesizing DNA molecules during replication of DNA.
CRISPR-Cas9 System
They then established a “spell check” system for the bug using CRISPR-Cas9, a popular human genome editing tool. The technology proved to be a big one in 2016, showing how it can perform a wealth of functions from helping treat hemophilia in mice to creating mushrooms that don’t turn brown easily.
The team used the CRISPR tool to make sure that any cells dropping X and Y would be tagged as a foreign invader, marked for destruction by the organism.
Astoundingly, the semi-synthetic organism was able to keep the synthetic base pair in its genome after 60 rounds of division, inspiring hope in the team that it can indefinitely hold on to the base pair.
Romesberg clarified, however, that their work is only in single cells and not meant for more complex ones, with zero application at the moment — meaning they can only get the organism to store genetic data at present.
The next step is to see how the new genetic code can be transcribed into RNA, which is the molecule necessary to translate DNA into proteins.
Synthetic biology expert Paul Freemont from Imperial College London dubbed it a major step in showing how we can engineer a living cell, such as a bacterium, to sustain a base pair not found in nature. This pursues the possibility of semi-synthetic living organisms performing certain functions “that would rely on a distinct genetic code.”
The findings were discussed in the journal PNAS.
