Expanding the Genetic Alphabet

The Scripps Research Institute has conducted a study on the DNA replication and found that the genetic instructions in living things is wider and varies more than just the four natural bases that are currently known- adenine, thymine, cytosine, and guanine. This expanded DNA alphabet that was discovered can carry more genetic information than the natural bases and thus, code for more molecules. This study which was in the issue of Nature Chemical Biology has show how these bases can go through the replication process as normally as the four bases. Floyd E. Romesberg, associate professor at Scripps Research, principal developer of the new DNA bases, and a senior author of the new study states that "We now know that the efficient replication of our unnatural base pair isn't a fluke, and also that replication is more flexible than had been assumed."  In the year 2008, Romesberg discovered the two efficiently replicating bases, NaM and 5SICS. They pair up together as a double helix just as normally as guanine pairs with cyotosine and guanine pairs with adenine. Then, Romesberg demonstrates in his lab that these two bases can be transcribed into RNA in the lab dish. However, their base pairing success still remains a mystery since it is clear that their chemical structures lack the ability to form hydrogen bonds like those that join the natural base pairs. In addition, the two pairs does not adhere to the Watson-Crick geometry of base pairing because they do not bond but rather join in a loose, “intercalated” fashion. First it was thought that this ‘mispair’ bases will not be recognized by the DNA polymerase during replication, but it was false since after several tests, the NaM-5SICS pair was replicated efficiently. Further support shows that even though the base pairs did not maintain the Watson-Crick geometry, but they do adopt the structure when gripped by the DNA polymerase during replication. Maylshev says that, “The DNA polymerase apparently induces this unnatural base pair to form a structure that’s virtually indistinguishable from that of a natural base pair.” The two bases which are not held by hydrogen bonds are instead held together in the double helix structure by “hydrophobic” forces. This causes the bases to repel water molecules and thus cling together in a watery medium. "It's very possible that these hydrophobic forces have characteristics that enable the flexibility and thus the replicability of the NaM-5SICS base pair," said Romesberg. 


http://www.sciencedaily.com/releases/2012/06/120603191722.htm