Editor’s note: Nature versus nurture; you’ve heard the expression. It makes the entities it juxtaposes seem like oil and water, distinct—with no chance to mingle. Now, however, we’re beginning to understand that environmental factors—like particles in the air or the food we eat—can actually influence how our genes, our very nature, are expressed. (Even identical twins, born with the exact same genes, can grow up to be different; one might get cancer, the other won’t.) When it comes to understanding our physical traits then, it seems our genes are just part of the story…
Why do these identical twins look different?
Trillions of cells make up your body. Even though each one has the same DNA sequence—or underlying genetic coding—not every cell looks the same. For instance, cells that make up your skin are different than neurons in your brain. One reason for this is that, for a given cell, every gene in it can be expressed at a different level.
For the purposes of this blog, each gene can be thought of as being on a dimmer switch—either turned on full blast, turned off, or set somewhere in between. If you fiddle with the thousands of dimmer switches corresponding to individual genes in each cell and set them to different levels, you get very different cellular environments. (Stem cells are often touted as so promising because they are cells at a stage before any of the switches have been adjusted, so they can become any type of cell.)
Now, scientists are discovering that the dimmer switches are not set on a permanent course; that is, the genetic code with which a person starts life may not be the only factor that dictates how that person develops.
Consider, for a moment, identical twin mice. Note that identical twins have the exact same genes. Both mice have a particular gene that causes obesity, but in the first mouse, it stays on constantly. What accounts for this? Does the first mouse run less on his multi-colored wheel, or does it have a high-fat diet as compared to its twin?
Nope. Instead, it is due to a small chemical “tag” of carbon and hydrogen, called a methyl group, which is stuck onto the obesity-causing gene, causing it to stop working. Organisms like mice and humans have millions of such tags. Some tags are hitched directly to genes, impeding the genes to function. Other types nestle in the proteins—called histones—that genes coil around genes; these tags can tighten or loosen their hold, impacting gene expression.
Distinctive methylation and histone patterns can be seen in every cell, constituting a sort of second genome, called the epigenome. The epigenome (which, literally translated, means above the genome) is like the dimmer switch overseer that tells the genome how to work. As mentioned above, it also tells our cells what sort of cells they should be—neuron, hair, skin, etc.—so we ultimately have all the cells we need. When we have enough of those cells, at a given period in our life, it silences the genes that produce them.
Research in epigenetics is helping to elucidate just how environmental factors—like tiny particles in the air or the vitamins we get from food—interact with our genetic material to cause differences in our physical traits. Air pollution and vitamins, for example, release chemical components that can create the “tags” described above. To produce thin mice instead of fat ones, a scientist could feed pregnant mouse moms diets rich in methyl groups to form the tags that can turn the obesity gene off.
Chromosomes are pieces of coiled DNA that contain many genes. Here, we see chromosome 1 in 3-year-old identical twins, left. At age 50, this same chromosome shows differences—differences caused by environmental factors.
Epigenetics is a hot topic now for several reasons. Beyond influencing cell type differences (as described above), it also creates patterns that are heritable, meaning they can be passed from cell to cell. A skin cell will divide into another skin cell, not a neuron cell, because epigenetic mechanisms set the dimmer switches in the new cell to parallel those in the parent cell.
Amazingly, this heritability is also intact from organism to organism. This means it is possible that your mother’s, or even grandmother’s, lifestyle choices played a role in your gene expression today—your eyesight, for example, or your respiratory heath. In the mouse example above, the epigenetic fix (feeding mothers food rich in methyl groups) could be inherited by the next generation of mice (or, the grandchildren), regardless of what their own mothers ate.
So, while you inherit your genome, you can alter your epigenome—and potentially that of your child. This has serious implications for how we live (whether we choose to smoke, for example, or eat a lot of bacon and forgo the vitamins in broccoli).
Epigenetics also has implications for medicine. The presence of the tags on the genome helps scientists discover the cause of diseases not explicable by DNA alone (indeed, changes to the DNA sequence used to be the first place scientists looked to explain diseases).
And unlike genetic mutations (actual changes in your DNA sequence), which have permanent consequences on gene expression, epigenetic changes are reversible—responsive to environmental influences. As a result, drugs could be designed to undo any deleterious effects from an epigenetic change. Say, for example, a tag controlling your genes caused certain cells in your body to become abnormal, triggering cancer. Epigenetic drugs could be made to reverse (or otherwise correct) the effect of the tag, thereby regulating gene expression to healthy levels. Some such targeted epigenetic therapies are already in place.
Research into the role of epigenetics in our lives, medicine and the pharmaceutical industry seems promising; indeed, aspects of it, like targeted drugs, are almost too good to be true. Check back very soon for an interview with a prominent member of the epigenetics community here in Boston, Dr. Andrea Baccarrelli, professor of Environmental Epigenetics at the Harvard School of Public Health. His answers gave me some perspective and grounded my wishful thinking.