DNA with three base pairs – A step towards expanding the genetic code

Scientists at The Scripps Research Institute in La Jolla, California are reporting today at the 229th national meeting of the American Chemical Society progress toward the creation of a system for replicating a modified form of DNA containing an unnatural base pair.

According to the Scripps Research scientists, this finding is a significant step towards expanding the genetic code and the ability of DNA to act as an information storage and retrieval system in the test tube and in simple, engineered organisms, such as yeast or bacteria. DNA with three or more base pairs could find broad applications in a number of fields, including biotechnology, medicine, data storage, and security.

Instead of just the canonical base pairs “G-C” or guanine–cytosine, and “A-T” or adenine–thymine, the Scripps Research scientists’ DNA has a third pairing: “3FB-3FB” between two unnatural bases called 3-fluorobenzene (or 3FB). Unlike other unnatural base pairs, DNA polymerases are able to replicate this base pair, albeit with reduced fidelity. To improve replication, the scientists also reported the development of a system capable of evolving polymerases to better recognize 3FB in DNA. Using a selection system some liken to evolution in the test tube, they are creating their own “polymerase” enzyme able to replicate the unnatural DNA.

While the polymerase does not replicate the unnatural DNA with the same fidelity observed in nature, (roughly one mistake for every 10 million bases of DNA copied), its fidelity is reasonable (typically making only one mistake for every1000 base pairs). This is the first time anyone has been able to replicate unnatural DNA with fidelity against every possible mispair.

“We definitely are still working on improvements, especially in fidelity,” says Scripps Research Assistant Professor Floyd Romesberg, who led the research. “Nevertheless, we are now able to replicate unnatural DNA.”

The American Chemical Society, the world’s largest scientific society, is holding its national meeting in San Diego, CA, from March 13 to 17. The talk on this research, entitled “Efforts to Expand the Genetic Code,” will be presented at 3:15 PM, Monday, March 14 during the Biomimetic Polymers symposium (POLY 193) at the San Diego Marriott in the Manchester rooms 1-2.