I have written about DNA before (regarding proteins and in the context of crime scene investigations). What I have not broached yet is the physical constitution of the DNA molecule. The media (appropriately) keep things simple when a news story involves genetic concepts by talking about “letters”. DNA is the “code of life” made up of “letters”. Well, that’s all fine and well for broadcast television, but nobody really believes miniature scribes have painstakingly been writing the longest book in the history of the world using a four-letter alphabet. So what does DNA actually look like?

Our roadmap for the article. The various layers of DNA condensation. From Wikipedia article “Chromatin”.

If we were to zoom in on a skin cell, we could go straight into the nucleus, the yolk of the egg-like cell if you will. We will bypass the mitochondria for now, tiny energy factories outside the nucleus which also contain DNA. We will concern ourselves with nuclear DNA for the moment.

Inside this nucleus, we see, among other things, the world’s maddest roller coaster. The DNA molecule looks like it exploded all over the inside of this giant dome. It swirls, and dips, and curls up, and twists. It is being held in place by specific anchor points on the surface of this nuclear dome. All over this insane structure, little proteinic carts rush by, replicating this immense genome as if a similar theme park were to be built next door. You would be hard-pressed to identify the various chromosomes you may have seen in a magazine article at some point: those condensed “X”s are not present at this stage. It is as if the chromosomes have been scrambled and all we can see is the totality of the genome all around us.

As we get closer to a particular portion of this roller coaster (which is known as the “chromatin”), we notice an incredibly intricate scaffolding made up of proteins. We move in even closer and notice that the simple roller coaster track we thought we were observing is actually much more complex than meets the eye. It consists in actuality of a tightly packed fibre coiled into a dense spiral 30 nanometers in diameter (or, if you prefer, 1/50^th the diameter of a thin flaxen human hair). This compact fibre is less interesting as its genes are not expressed to the best of our knowledge, but as we move along, we notice a length which is quite decompressed. The fibre has been stretched out into a single filament occasionally wound around a wheel-shaped particle made up of eight proteins. These individual bodies, with the filament wound around the wheel, are called “nucleosomes”, from the Latin for “nuclear bodies”.

The reason the fibre relaxes into this more open form is to allow access to a variety of proteins which will transcribe portions of this DNA into what will eventually become… more proteins. The dense 30-nanometer fibre, by contrast, is essentially inaccessible to the transcription apparatus: it would be like trying to read a book the pages of which have been glued together.

When we approach the loose filament which occasionally shapes itself around the proteinic wheel of the nucleosome, we recognize something: the double helix. Here it is, at last, after all these layers of compaction, the world famous double helix of DNA discovered by James Watson and Francis Crick… and Rosalind Franklin and her Ph.D. student, Raymond Gosling. Franklin’s student took the famous picture which showed the characteristic X-ray diffraction pattern of the DNA molecule. The story gets more complicated, as multiple pieces of evidence were acquired by different people, including Maurice Wilkins, who collaborated with Watson and Crick. In the end, the Nobel Prize went to Watson, Crick, and Wilkins. Rosalind Franklin, the only woman in this lot, was deemed ineligible since she had passed away four years before the awarding of the prize. To this day, the Nobel Prize cannot be awarded posthumously (the only way around this is if the nominee dies in between the announcement and the ceremony, as in a heart attack during the phone announcement, for example).

If we move away from the nucleosome and zoom in on this helical filament of DNA, we can see its basic structure. The DNA molecule consists of three elements: phosphate, sugar, and a ring or two. Unwinding this double-helical spiral yields what looks like a traditional ladder. The side pieces of the ladder are made of individual sugar molecules, deoxyribose, which are joined together by phosphate groups. If you were to remove the rungs of this ladder and slide down the remaining pole, you would encounter deoxyribose bound to phosphate bound to deoxyribose bound to phosphate… all the way down. The linking phosphate groups carry a negative electrical charge, which is why the DNA molecule is negatively charged.

What brings the two side pieces of the ladder together—the rungs—are the “bases”. These are the “letters” of the DNA code and represent the information content of this important molecule. A base is simply a chemical molecule made of a specific arrangement of carbon, hydrogen, nitrogen, and usually oxygen atoms. All four bases present in DNA are cyclic, that is some of their atoms end up forming a closed ring. Cytosine (C) and thymine (T) have one ring; adenine (A) and guanine (G) have two.

What’s interesting here though is the concept of complementary base-pairing. This means that the adenosine molecule can form an electromagnetic bond with a thymine molecule (A-T), whereas a guanine molecule can form a similar though even stronger bond with a cytosine molecule (G-C). As we pull back and identify each base on our floating DNA helix, we notice that, indeed, if one half of the rung is an A, the other half is a T. Therefore, the double helix is redundant: the information carried on one helix is complementary to the information carried on the other one.

If we were to get really excited and move in even closer on one of these bases, we would see that, really, in the end, we are all bits of carbon. The ring is made up of carbon atoms and the odd nitrogen atom, with hydrogen here and there. These carbon atoms are composed of six electrons spinning around a nucleus of six protons and six neutrons… and those protons and neutrons are each made up of three quarks. So, as we quickly pull back, we see the quarks forming the protons and neutrons at the centre of carbon atoms, themselves creating the individual building blocks of the DNA double helix, itself wrapped around wheel-like structures, themselves compacted into a tight fibre which is surrounded by a complex protein scaffolding and which zigzags all over the nucleus.

“This is all fine and swell”, I hear you say, “but was I taught a lie? Isn’t our DNA separated into chromosomes?”

Chromosomes are ephemeral structures. They only come together as the nec plus ultra of DNA condensation at a very specific time in a cell’s life: just as it’s about to split. You see, unlike fully grown adults, cells don’t replicate in a 2:1 ratio, but rather a 1:2 ratio, as in one cell begets two. Once a cell has duplicated all of its DNA, chromosomes form and they align along a central plate, as if they were about to line dance. One set of chromosomes goes one way, the other goes the other, the cell splits, and voilà! Two cells. The chromosomes decondense, and we are back to that crazy roller coaster called the chromatin.

The degree of structural engineering required to condense this chromatin is not only impressive but necessary. Even though our cells are microscopic, on the order of 0.001 to 0.1 millimetres in size, the length of DNA they each carry is mind-blowing. It has been estimated that the total length of DNA in each of these microscopic cells is roughly 2 metres. If you could take the DNA from every cell in the human body and align it end to end, you could span the distance from the Earth to our Sun 70 times….

(Feature picture by EMSL)