DNA is made from four nucleosides, each known by its own letter -- A, G, C, and T. However, since the structure of DNA was deciphered in 1953, scientists have discovered several other variants that are often added to the DNA sequences to replace one of the usual four letters. These variants, which may be modified versions of the traditional nucleosides, often help cells to control which genes are turned on and off, and are referred to as "epigenetic marks" in the DNA. In bacteria, they can also protect DNA from invasion by other organisms such as viruses.

Until now, these DNA modifications have been discovered by chance, as scientists uncovered unexpected signals in chemical analyses of DNA. However, a new approach from MIT, the University of Florida, and other institutions offers a systematic approach to discovering unknown epigenetic marks and modifications.

"It's a way to discover nucleic acid modifications that you didn't know existed," says Peter Dedon, the Underwood-Prescott Professor of Biological Engineering at MIT. "We've developed a technology platform for the discovery and characterization of these new modifications."

Dedon and his colleagues suspect that bacteria and viruses, in particular, have many DNA modifications that have not been discovered yet, which could offer new antibiotic targets and new tools for biotechnology. Using their approach, which combines bioanalytical chemistry, comparative genomics, and a special type of DNA sequencing, the team has discovered a DNA modification that helps bacteria to protect their genomes from viral infection. They report the findings in the Proceedings of the National Academy of Sciences the week of Feb. 29.