Once upon a time, Brandon Keim notes, researchers knew that DNA contained four nucleotides. Then they found a fifth. And now they’ve found a sixth:
Called 5-hydroxymethylcytosine, it’s a form of the fifth nucleotide, technically known as 5-methylcytosine. Like its forerunner, it helps turn genes on and off, but in ways that researchers didn’t expect.
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Epigenetics, or the study of gene activation, has blossomed since the Human Genome Project’s completion in 2004. Controlled by a secondary layer of biochemical information — “epi” means “outside” — genes are turned on and off at different times and places in the body. That helps explain why, despite considerable genetic overlap, species take such different forms. (Humans and chimpanzees famously share 96 percent of their DNA.)One powerful epigenetic mechanism is methylation, in which 5-methylcytosine replaces cytosine — the letter C — in a gene, telling the cellular machinery that turns genetic code into proteins to leave it unread. Heintz made his findings almost accidentally while developing new methods for studying methylation in mouse neurons.
According to Heintz, methylation performed by 5-hydroxymethylcytosine doesn’t behave in the same way as that produced by old-fashioned 5-methylcytosine. And just to make the situation trickier, standard methods of methylation detection can’t distinguish between the two forms.