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My Kingdom for a Methyl Group

The simplest organic functionality of all is the humble methyl group. A single carbon and three hydrogen atoms seem relatively small and insignificant compared to most full-blown organic molecules.

You might even think that a methyl group here and there would hardly be noticed in the vastness of very large molecules like DNA. And if you did think this, you would be wrong.

Take the case of identical twins. They start life with exactly the same DNA, so it would seem to follow that their susceptibility to genetically based disease would be the same. If your twin had high blood pressure, got cancer, or suffered from lupus, you would, too.

In theory maybe this would be true, but in real life twins are often “discordant” in the traits they express. For example, when one twin has lupus—a disease in which the immune system attacks the body’s own cells—more often than not the other twin remains healthy.

A new study suggests the explanation may lie with the lowly methyl group, or more precisely the pattern of methylation of DNA. Reporting in Genome Research, Javierre et al. show that a healthy twin whose identical sibling has lupus has a decrease in DNA methylation in at least 49 different genes (letter published online 22 December 2009). Thus, while the inherited DNA base sequence may read the same, the methyl punctuation marks don’t, and this leads to alterations in gene expression.

This is a vital clue to a nasty disease. But alas, we don’t yet know what causes the methylation to vary, or what to do about it therapeutically. 

The study does point to the importance of non-inherited factors, probably environmental ones, that dictate outcomes. Once again the resolution of the nature vs. nurture debate falls squarely in both camps.

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Periodic Tabloid is an ongoing record of the activities of the Chemical Heritage Foundation’s staff and scholars, whose work tells the story of chemistry over the centuries up to modern times. Stay tuned for behind-the-scenes coverage of our events, exclusive supplemental materials to our publications, analysis of pressing contemporary scientific issues, and much more.