Above Genetics: How Epigenetics Reconstructs the Destiny Written by Our Genes
by Nicole Aeronne S. Cura
“You can think of epigenetic tags as punctuation marks in a sentence if our DNA sequences are considered the letters. Like these tags, each punctuation mark provides instructions on how sentences should be read and interpreted without altering the words that are used.”
We have always been fascinated with identical twins. It is easy to get intrigued by how similar they are, as we typically see twins with matching dresses, hairstyles, and even names. Geneticists, however, are more interested in how different identical twins can be when they technically share the same genetic information. Seeing as everyone often expects twins to behave alike, how, then, do we tell the difference between them?
Why do identical twins, originating from the same DNA, have different genetically influenced diseases and conditions? Why and how do they have differences in their preferences? Why can one twin want to go to law school while the other wants to go to medical school?
Such distinction may seem strange. They are identical, after all. Moreover, they don’t only share the same genome but also the same home environment and upbringing that could enhance their similarities. Their nature and nurture are essentially parallel, yet they grow to become two distinct individuals! Well, as it turns out, their shared DNA and environment are not the only factors that affect their behaviors, as a third and more assertive determinant, called epigenetics, also sets them apart.
The Epigenetic Tags
Epigenetics literally means “above genetics,” as it provides information beyond the sequences of our DNA. It is the study of how our DNA interacts with the smaller molecules found within our cells to determine which genes should be expressed and which should be regulated. This tells us that several alterations in our gene expression modify our cellular functions without changing the nucleotide bases in our DNA. These modifications are denoted by epigenetic marks or the chemical tags that sit upon our chromatin to instruct the activation of our genes. You can think of epigenetic tags as punctuation marks in a sentence if our DNA sequences are considered the letters. Like these tags, each punctuation mark provides instructions on how sentences should be read and interpreted without altering the words that are used.
Commonly, epigenetic markers appear in three different forms: DNA methylation, histone modifications, and nucleosome positioning. They are present in the genetic material of all individuals, and they usually begin to appear early in our embryonic development. It is actually one of the reasons why our initial embryonic stem cells had differentiated to become specialized cells, like our neurons and blood cells, even when all of the cells in our body have the exact identical copies of DNA. It can also be why a fetus whose mother is suffering from malnutrition may show different DNA methylation patterns in various gene segments, which may result in growth and metabolic disorders later in their life.
Aside from these adjustments, epigenetic modifications can also occur after birth. For instance, lactose intolerance or the inability to digest milk sugars is more common in adults than in children. It’s because this impaired ability generally does not manifest in children until they lose the capacity to produce lactase. It was reported that aside from the T-allele (responsible for lactase persistence), epigenetic signatures along the LCT gene (lactase gene) differ among lactose tolerant and lactose intolerant individuals depending on their exposure to lactose after weaning. This simply implies that the changes that occur in our epigenome are, in fact, influenced by the surroundings to which we are exposed.
Contributions of Twin Studies on Epigenetics
Twin studies have contributed in uncovering the influence of environmental and genetic factors in the epigenetic profile of an individual. For identical twins, their prenatal epigenetic profiles and their early childhood epigenomes are said to be indistinguishable. However, as they grow old, they eventually have to experience different environments, which can individually modify the genomic distributions of their epigenetic tags. This gives an excellent understanding of how epigenetic mechanisms such as DNA methylation can change certain traits without being confounded by the divergence in the DNA sequences.
For instance, rheumatoid arthritis (RA) is a multigene disorder that causes inflammation of the joints of the hands and feet. Substantially, four genetic markers are linked to RA, yet there is an observably high rate of discordance in the development of the disorder in identical twins. If one twin contracts RA, there is only a 12–15% chance that the other twin would also get it. Since identical twins don’t always get the condition in concordance, we can say that there are possible additional variables to the multigene disorder. It was found that twins suffering from RA have less predictable DNA methylation patterns, as the four specific gene regions linked to RA were observed to be hypermethylated.
Cellular stress was determined to be a primary factor in the changes observed in DNA methylation, and this can be influenced by exposure to environmental toxicants, such as smoking, and improper nutrient habits like excessive alcohol consumption. Considering this, differences in DNA methylation between twins help investigate the effects of environmental factors on the development of the disease without the possible limitations of genetically driven changes.
Identical twins may share the same genes, but their environment inevitably becomes more different later in their lives. For this reason, they also develop more noticeable differences, physically and behaviorally, as they age, which helps our geneticists gain more insights into the influence of epigenetic processes in our development. We may not be able to tell how twins differ at first sight, but once we take a closer look at the molecular level, we see that each individual, even twins with identical DNA, is unique.
