Beyond the genome, part 2

The December issue of Scientific American finishes its two-part article about parts of the genome that have definite influences on how genes are expressed and how health may be affected as a consequence. Last month’s episode explained why some stretches of DNA thought to be “junk”—DNA accumulated down through evolution but having no contemporary impact on what happens in our cells—are not junk at all. Some DNA produces sequences of RNA that can stifle protein production in a ways that have important outcomes.

The article currently on newsstands has more about more “epigenetics,” chemical interactions surrounding DNA in the chromosomes that also can turn on or turn off the output of the genes. You might be thinking: “So what?” The answer is that epigenetic events have a definite role in cancer. There’s more involved in the lengthy process of going from normal cells to malignant ones than mutations in the protein-producing part of the genome. Although these processes that affect gene expression haven’t gotten as much press as mutations, they do play a role in progression of cells from normal to malignant.


Francis Collins, director of the National Human Genome Research Institute says about epigenetics, “Clearly for cancer, for development, for birth defects, it is a very important phenomenon.”

We’ve all seen animations of DNA doing its job: the DNA double helix untwists; molecules connecting the sides “unzip” like teeth of a zipper; molecules float in and, almost magically, fit into the teeth to create a kind of reverse copy of the unzipped ladder; and, finally, the new template for protein formed by this matching float off to do its work. But that uncomplicated, serene cartoon bears only a passing resemblance to the reality of actual events going on in our cells at every moment.

One important thing not shown in most enactments of molecular interaction is that, along the DNA helix, molecular clumps called a “methyl groups” are attached to DNA molecules, especially cytosine, the “C” in the famous A, G, T, C quartet of molecules which make up DNA sequences. Methyl molecules play an important beneficial role in “silencing” the expression of certain genes. Their presence is part of the normal “regulation” of how and when genes are available to produce the proteins that make us up. On the other hand, too much methylation of specific genes that themselves play a role in stopping deranged cells from becoming malignant may play a role in enabling cancers to progress. Evidently a critical balance of methyl molecules is important. The right amount in the right place at the right time is healthy; other combinations may contribute to disease.

Another molecular group—acytl molecules that attach to proteins in chromosomes and play a vital role in spooling the DNA helices—do a similar dance affecting which genes produce proteins and which are silenced. More epigenetics. If it sounds confusing that’s because it is. Scientists have not gotten all the details straight. Much is still hypothetical. In fact, just recently a large-scale, five-year effort called the Human Epigenome Project started to chart the likely places in the genome where active RNA, methyl groups, acetyl groups and other chemistry play a role in gene expression.

So why bother to know about this? Because, as we continue to wait for better treatments for cancers or for chemicals that can prevent some forms of the disease, it might be helpful to understand that there are multiple layers of complexity involved in the genome. It would be nice, perhaps, if genomics was simpler. It would be nice if straightforward answers and treatments had come out of the Human Genome Project. But the fact is the basic unit of life, the cell, is more complicated than that. In addition to all the genes there are subtle, more transient processes such as RNA from the “junk” zone of the genome and “epigenomics” of methyl and acetyl molecules involved in what happens.

When the public asks impatiently, “When are they going to find the cure?” it might be helpful to know that very dynamic events are involved. The process of understanding will continue to take time and the resulting interventions might be complex as well.

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