In the “nature vs. nurture” debate, those in the former camp believe that who we are, from our physical traits to our propensity for disease, is largely predetermined by the genes that we inherit from our parents. The nurture side attributes much of who we are to our environment.
Recent research shows that this age-old debate is far too simplistic. Nearly every cell in the body contains complete identical copies of our DNA—the body’s instruction booklet for some 20,000 genes. But what exactly determines which of these genes are expressed and which ones are not? While the body’s master instruction booklet can tell us a lot about who we are, how this book gets interpreted may tell us even more.
The rising field of epigenetics seeks to answer these questions. Sure, we’re all born with a predetermined set of genes, but a variety of factors from exposure to environmental toxins to how much we're cuddled as a baby can influence how these genes are expressed. A growing body of research suggests that epigenetics can influence whether we develop diseases such as cancer or lupus, and plays a role in development of our personality and mental health.
The Instructions of Life ‘on Top of’ Our DNA
The field of epigenetics was first established in 1942 by British developmental biologist Conrad Waddington, who was fascinated by how biochemistry influences how genes are expressed. The term “epigenetic,” which literally means “in addition” or “on top of” genetics, refers to a variety of biochemical changes that occur on the outer surface of DNA or on packaging proteins around which DNA is wrapped that turn gene expression on or off. Such biochemical modifications can be inherited and can remain in place as cells divide, but external influences can affect these processes, too, in negative and positive ways: Physical exercise can increase the expression of genes involved in tumor suppression, for instance.
In 2015, more than a decade after the entire human genome was first mapped, the “Roadmap Epigenomics Program (REP)” unveiled maps for the epigenomes of 111 different cell and tissue types. This complex data set identified epigenomic patterns associated with a variety of traits, from blood pressure and cholesterol to our propensity for Alzheimer's disease.
“Deeper understanding of epigenetic modifications and their corresponding changes in disease can help guide treatment strategies."
One of the most well-studied epigenetic processes is DNA methylation, which refers to the addition of a methyl group (CH3) to certain areas of DNA that can turn off, or “silence,” a gene. As obscure as it may sound, this process—DNA methylation-mediated gene silencing—is an essential part of key biological processes in mammalian development, such as cell differentiation, X-chromosome inactivation, and even immune system regulation, explains Shikhar Sharma, Senior Principal Scientist at Pfizer's La Jolla, CA, site.
At the same time, says Sharma, “Unusual DNA methylation patterns are associated with diseases like cancer." For example, he explains, "The entire cancer epigenome is typically hypomethylated," meaning that it lacks a methyl group, a trait that leads to genomic instability. He adds, "Another trait of the cancer epigenome is that genes that suppress tumors tend to be hypermethylated, which results in those genes being silenced." Researchers are now studying DNA methylation signatures for both cancer diagnosis and prognosis, he says, and developing therapeutic approaches aimed at reversing the effects of DNA methylation on tumor progression.
More Cuddles for a Healthier Epigenome
One recent study from the University of British Columbia in Canada found that how much an infant is touched and cuddled can impact their epigenomes, leading to lasting changes in gene expression. The study of 94 healthy children found that those who had less physical contact as infants showed markers for changes in DNA methylation that showed up in follow-up studies four years later. This group showed “epigenetic age” deviation, which could potentially have an impact on their health and development later in life.
The good news about epigenetics is that we may also have more control over our fates. Unlike our DNA, which is a book that has already been written and cannot be rewritten (except for gene therapy), the epigenome can change. Lifestyle factors, environmental exposure, nutrition, etc. can possibly influence epigenetic modifications leading to changes in gene expression. “Deeper understanding of global patterns of these epigenetic modifications and their corresponding changes in disease can help guide treatment strategies that could reverse such epigenetic anomalies to their normal state," says Sharma.