It's not all in the genes

Garlic, vinegar, soy sauce, and meat — the basic ingredients of adobo. Still, have you ever wondered why your mom’s adobo will always be better than that of others? Or why adobo will never taste the same when cooked in other places — for instance, the American adobo?

The same thing happens to our body. We know that our DNA sequence determines our appearance — our skin color, hairline, nose height. Change a sequence and one can most likely expect a change in features. Yet, all of our cells contain the same DNA sequence, but one cell becomes the arm, another cell forms the neck, and so on. Moreover, twins have identical DNA, yet we can still tell them apart from each other.

Just as food tastes different despite using the same ingredients, our DNA is expressed differently despite having the same sequence.

Before we can understand how this happens, we must first see the DNA beyond its double helix structure. The entire DNA in one cell can reach two meters. We have 10¹³ cells. Do the math and it will give us DNA that can do 70 trips from the earth to the sun and back.

How did this two meter-long DNA fit into a very tiny 10 µm nucleus of the cell? Think of the DNA as a thread wound around a spool made of proteins called histones. Around each spool are 147 base pairs of DNA. These spools are then connected by a 10-base pair long DNA. This first level of structure of chromatin — a complex of protein and DNA — is aptly called “beads-on-a-string.” Adding another histone coils the “beads-on-a-string,” forming a structure similar to a very compressed spiral telephone cord. Incorporation of other scaffold proteins further compacts the DNA to a very dense chromosome, the X-shaped structure we normally see on television.

Obviously, histone proteins are necessary to pack the DNA into the cell nucleus. However, equally important is their role in regulating the expression of DNA.

Histones are tagged by enzymes with molecule groups such as acetyl and methyl. This causes the modification of the chromatin structure. For example, since opposite poles attract, the positively charged lysines of the histones prevent the repulsion of the negatively charged DNA from each other. Tagging of the histones with acetyl neutralizes the positive charge, enabling the DNA to repel. This opens up the chromatin allowing proteins to bind and express the DNA. Like a simple game of hide-and-seek, the more conspicuous you are, the simpler it is to tag you.

Another form of regulation is attaching methyl groups to DNA. This may either prevent the binding of proteins for expression or attract the binding of enzymes for histone modification. Thus, DNA methylation may hinder the expression of genes.

These illustrate that the accessibility and arrangement of DNA around the histones determine which genes are switched on or off by making them “easy to get” or “hard to get” for proteins.

Histone modification and DNA methylation control our physical features without changing the DNA sequence itself. This phenomenon is called epigenetics. Similarly, the amount of spices, the time of simmering, the temperature of the flame, the freshness of meat — these are factors that alter taste when cooking without changing the ingredients themselves.

It is epigenetics that allows our cells to have distinct characteristics, despite having the same DNA sequence, by regulating which genes are expressed in some cells and silenced in others. Having 30,000 genes, this regulation is extremely important, as we would not want to grow an arm where our leg should be.

Epigenetics also plays a role in diseases such as cancer, dementia, drug dependence, and many others. In cancer, DNA methylation silences the genes that normally control and suppress the overgrowth of cells. The gene cannot do its job, cells can’t stop growing, and cancer ensues. Epigenetics may be a better target for treating cancer because it is easier to regulate rather than attempt to nullify the effects of mutations in the DNA sequence. In fact, drugs that inhibit or reverse this methylation on DNA show very promising results in patients with certain types of lymphoma and leukemia.

Epigenetic tags may be activated on our genome by responding to environmental conditions such as stress, diet, behavior, and toxins. Thus, epigenetics makes identical twins not identical because, although they have the same genetic make-up, they eat different food, have a different set of friends and feel different emotions.

When these epigenetic tags occur in egg or sperm cells, they are stable and are passed on to the offspring when these cells unite. This indicates that not only do we inherit our parents’ genes but also their epigenetic features and way of regulating gene expression. When mothers in the Netherlands were starved during World War II, they gave birth to relatively small children. These children, in turn, also gave birth to small children despite living a comfortable life. The shortage of nutrients of the mothers limited their sources of methyl groups resulting in an incorrect pattern of DNA methylation. This was inherited by their children and even by their grandchildren, affecting their growth and development. “Past is past” may not exactly apply to the body, eh?

There are many other epigenetic mechanisms regulating our DNA — as many as the ways of cooking the Philippine adobo. Same recipe, different taste. Same genome, different epigenome. Genes are extremely important but, contrary to popular belief, it’s not all in the genes.

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The author is taking MS Molecular Medicine at the St. Luke’s College of Medicine-William H. Quasha Memorial (SLCM-WHQM). She graduated with a BS Molecular Biology, summa cum laude, from the National Institute of Molecular Biology and Biotechnology (NIMBB), UP Diliman in 2008. She can be reached at [email protected].