You very likely remember from high school biology the story of Gregor Mendel, the monk who in the mid 1800s observed that the inheritance of traits among pea plants in his garden was not random but seemed to follow certain patterns or laws. Despite his discovery, however, he knew nothing about the mechanism by which his pea plants transferred this information, their genetic code. We now know it is as the molecule DNA, deoxyribonucleic acid.
(Your other memory from biology class likely is this famous black and white picture of Francis Crick and James Watson standing next to a model of DNA, representing their discovery of the structure of DNA in 1953.)
Science has rapidly progressed and within the last ten years the Human Genome Project has unraveled the full sequence or code of human DNA; yet, despite knowing the full sequence of DNA there is a lot in humans we still can't explain, predict, etc. We haven't licked human disease. Why is that? What more to the puzzle could there be?
Let me address one aspect of this puzzle: epigenetics.
How is it that in your body the exact same DNA, or code, is present in your liver cells as in your brain cells and yet the two cell types are very different? Or that identical twins share the exact same DNA and yet are different individuals, even if subtly so? Clearly, the answer to these questions is not simply DNA.
The answer instead partly lies in how the DNA is read or expressed in cells. One mechanism: regions of the DNA are made more or less accessible to being read. Two people allowed to read different sections of an encyclopedia will walk away with different knowledge.
For instance, a cell may attach or associate certain chemical groups or molecules (such as methyl groups) to certain regions of DNA and, thus, alter the structure or reading of those regions but in no way change the DNA sequence itself. These modifications are not part of the DNA (or genome) itself, but 'outside' or 'above' the DNA, and make up what is called the epigenome (from the Greek meaning literally above the genome or DNA).
In this way the epigenome, despite not being the actual code or DNA sequence, plays an important role in cells. Knowing the DNA sequence is not sufficient. What is also important is how the DNA is expressed.
Two prominent examples of the epigenome's effect on the human body include X-chromosome inactivation and genomic imprinting.
X-chromosome inactivation
Quick review: In general the cells of our body have two copies of DNA, one copy inherited from our mother and the other from our father. In order to fit into our cells, the DNA is packed up and organized as chromosomes, and human DNA consists of 23 pairs of chromosomes (again, one pair from each parent). The sex chromosomes (denoted as either X or Y) are the chromosomes that determine our sex, whether we'll be male or female. A person born with two X chromosomes is born as a female.
For years scientists have known that in any given cell of a woman, only one of the two X chromosomes (either from her mother or father) is generally expressed while the other is inactivated (not expressed). This inactivation (X-chromosome inactivation) appears to occur randomly, such that in one cell the mother's X chromosome may be inactivated and in another cell the father's X chromosome. It occurs as a result of changes to the epigenome, which allow only one X chromosome in each cell to be read despite both X chromosomes being present. Once set this inactivation and epigenetic changes are passed along as the cell divides.
Genomic imprinting
Another exception to the idea that we are essentially the expression of both our mother's and father's DNA, because each cell contains a copy of DNA from each parent, is genomic imprinting. For some locations on the DNA, who we are is determined not by both the mother's and father's DNA but by either the mother's or father's DNA. The DNA from one parent is silenced, not read or expressed due to genomic imprinting, parent-specific epigenetic changes of that DNA location.
Angelman syndrome and Prader-Willi syndrome are two examples in which genomic imprinting manifests in humans. Prader-Willi syndrome has captured some attention as many patients suffer from truly insatiable appetites that require their families to lock the refrigerators and remove all other food from the house.
Imprinting may play a role in other more complex disorders, including bipolar disorder.
Epigenome and the environment
What scientists are trying to understand now is to what extent the epigenome plays a greater role in humans.
The epigenome in our bodies is not permanent and, in contrast to our DNA sequence, is more malleable to change. One theory posits that this ability of the epigenome to change developed as a mechanism to assist us in adapting to our environment. For instance, if a child were born into a period of drought and starvation, there would be a benefit if the child were adapted to such an environment. Evolution, which occurs over many years and generations, however, would be of little use to this child.
Animal studies and human epidemiological (population) studies suggest that the environment during our time in the womb and shortly after birth affect our risk of developing various diseases later in life, leading some scientists to question whether the epigenome is to blame. Does the environment alter our epigenome and thus affect the long term expression of various parts of our DNA with repercussions later in life? To return to our example, changes made early on to adapt to starvation could be detrimental if the child is later exposed to plentiful food.
A well-known experiment in mice involves a location on the DNA in mice (called the Agouti gene) that plays a role in the color of their coat. In certain mice who have a variation of the Agouti gene, Avy, the color of the coat is related to the degree of epigenetic changes (methyl groups) that have been added in variable fashion during pregnancy, allowing mice born with identical DNA to have different coat colors, from yellow to brown. The extent of added methyl groups affects the expression of the DNA. Mice with few methyl groups added to this portion of DNA have yellow coats (and appear predisposed to obesity) while those with numerous methyl groups have brown coats.
What scientists discovered is that if they fed the mothers vitamins and other supplements considered “methyl-donors” (thought to promote the addition of methyl groups) during pregnancy, that they increased the number of brown mice born. This finding was true as well when the mothers were fed a phytoestrogen (a component of some plant foods that act like estrogen in parts of the body) called genistein, which at levels seen with high soy diets is also known to increase the amount of methyl groups added to DNA.
Epigenome and cancer
The epigenome may also have a role in cancer. There are certain parts of the DNA in every cell that promote growth (oncogenes) and that inhibit growth (tumor suppressor genes). In a well regulated cell there is a proper balance between these forces, but a tip in the balance of expression or lack of expression of certain genes can produce unregulated growth in a cell, or cancer.
Epigenome and behavior?
One mouse study suggests the potential inheritance of certain behaviors via the epigenome. In mice the mother's nurturing of her offspring (maternal instincts such as licking and grooming), is learned early after birth. (Mice that have been nurtured also appear as adults less fearful and better able to respond to stress.) Studies suggest that this nurturing occurs and is passed along due to epigenetic changes in the offspring during nurturing; the offspring grow up to be mothers and nurture their own offspring and continue the cycle.
In conclusion
The possibilities of epigenetics are eye-opening although a lot of questions still remain. To what degree is epigenetics, beyond a few examples, actually relevant in humans? If to a significant degree, then what in our environment affects the epigenome? Can we take advantage of this knowledge to prevent or treat disease? Eat certain foods or take certain vitamins? Or would such treatments be too indiscriminate and while addressing one disease possibly promote another?
For those interested in more detail:
Jirtle, Randy L and Michael K Skinner. "Environmental epigenomics and disease susceptibility," Nature Reviews Genetics, Vol 8 (April 2007), 253-262.
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