One of the most awe-inspiring features of life is that every organism, from the sophistication of Albert Einstein to the minimalist existence of the simplest bacterium, is coded for by a genome sharing the same set of four bases: A, T, G and C.
While there is an attractive mathematical elegance to the power of permuting just four bases into sequences as diverse as the genome of Albert Einstein and that of a bacteriophage, biology – as always – turns out to be a little more complicated than first appearances. DNA's complexity is underscored dramatically in this month's Genome Biology, in an article describing the genome-wide mapping of the "seventh base".
The reality of genomics is that the four canonical bases can be chemically modified in a number of ways, with diverse functional consequences. In mammalian cells, the methylation of C to 5mC has long been studied, although many aspects of this modification's function are still debated.
A sensational development in 5mC's study over the last two years has been revelations about the oxidative conversion of 5mC to 5hmC (dubbed the "sixth base" by many in the field). Last year, an oxidative product of 5hmC, 5fC (5-formylcytosine), was shown to be present in mouse DNA, leading to speculation that it too might play a functional role in the mammalian genome.
In the new Genome Biology article, the groups of Wolf Reik and Shankar Balasubramanian develop the first method for high resolution 5fC mapping and apply this approach to mouse embryonic stem cells. In addition to demonstrating the importance of 5fC in specific epigenetic reprogramming events, the article finds that excision of 5fC by thymine DNA glycosylase is a necessary component of 5fC function.
The presented mapping method opens the door to many future exciting studies on 5fC; given the prevalence of 5hmC in brain tissues, perhaps we will even discover that Einstein’s genius was, in part, a gift from the seventh base.