Take a minute and try to remember back to your high school biology class. From everything I’ve ever been told, DNA is comprised of four basic nucleic acids – cytosine, guanine, adenine and thymine. The way these four bases are connected are represented in the DNA strands you see in print sometimes that look a bit like a word search puzzle (TACGGCTACATGC and so forth).
But apparently that’s not the end of the story.
Like everything else in the world, these compounds are formed by specific atomic structures of the elements. And every now and then, a slight switch in the structure of cytosine results in the creation of a slightly different version of the base nucleic acid. So with the addition of 5-methylcytosine (5-mC), there are actually five different base nucleic acids used in DNA.
But apparently that’s not the end of the story, either.
In a new paper just published by the University of Chicago’s Chuan He, there’s a sixth nucleic acid, which is yet another minor alteration to 5-mC. In short, one branch of the molecule (H3C) is replaced with another (HO) to create 5-hydroxymethylcytosine (5-hmC).
Say that five times fast.
I’m not going to try to pretend that I really understand what all that means, or that I can even successfully pronounce all of that on a consistent basis. But this much I do know for sure – the use of these slight variations of cytosine makes a different.
The new paper describes a technique recently devised that allows researchers to map the presence of 5-hmC throughout the genome. It’s close cousin 5-mC typically is found on genes that are turned off and helps silence genes that aren’t supposed to be turned on. But it appears that this new version is enriched on active genes, especially brain cells.
Another difference with 5-mC is that 5-hmC is usually on only one side of the DNA. In contrast, 5-mC is most often found symmetrically. Overall, 5-hmC is around 14 times less abundant than 5-mC. Even at sites where 5-hmC is the most abundant, it is still present at about one fifth the frequency as 5-mC.
Also, previous research has found that 5-hmC is 10 times more abundant in brain than in stem cells, so it may have an especially important role there. The only way to find out is for future research projects that use this new technique to find when 5-hmC is present and how it affects the DNA of which it is a part.
Along with colleagues at the Ludwig Institute for Cancer Research, the University of California, San Diego, and Emory University, Chuan He intends to do just that.