Just when you thought you’d mastered both your linguistic and scientific alphabets, it looks like it’s time to dust off the ol’ learning cap and re-learn your ATGCs because the two-base-pair genetic alphabet has just got some fancy new characters. A clever team from the Scripps Research Institute in La Jolla (California) have now expanded the inheritable information storage capacity of the genome.
This project represented a colossal 15 year effort in which the team previously developed a class of ‘alien DNA’ or unnatural base pairs (UBPs), that could be incorporated into the genome and take Watson-Crick base pairing to a new dimension (A-T and G-C and now 5SICSTP-NaMTP). They also described how this duo can be efficiently PCR amplified and transcribed alongside the more traditional base pairs.
The researchers did have to overcome a few problems. First, the unnatural nucleoside triphosphates needed to get inside the cell. Second, the home team of polymerases had to be able to utilize these bad boys in order to faithfully replicate DNA containing the UBPs. Finally, the UBPs had to be able to withstand the constant beating of DNA maintenance pathways.
Here’s what they accomplished:
- A model system was built in E. coli and gave it a ‘borrowed’ triphosphate transporter from alga.
- This adapted transporter was able to move the unnatural triphosphate precursors, allowing for unnatural DNA synthesis to occur naturally.
- Under test conditions the system could be used to accurately replicate a plasmid containing the unnatural duo.
The team also made sure that the UBPs didn’t cause a “notable growth burden” and was never efficiently excised by DNA repair watchdogs, giving the crew an organism capable of transmitting an expanded genetic code. And while Cytosine and its entourage of modifications have taken the synthetic spotlight, it looks like genome editing may benefit one day from the added storage capacity of this synthetic multi-dimensional approach.
Think outside the natural limits in Nature, May 2014