DNA – three layers of information?

Some time ago in the “Jaw Drop #3 – A DNA’s orchestra” post I talked about how important DNA is for our lives. I emphasized what an extraordinary molecule DNA is both for its simplicity and for its utility. I remarked how nowadays everybody have at least heard of the “big molecule”, but unfortunately, most of us have no idea what it is, what it does or why is so special. The previous post wanted to explain in layman terms what it does and why it’s important, so this time I’ll focus on what it is and what’s special about it.

DNA or Deoxyribonucleic Acid, is a macromolecule composed of many elementary units called Nucleotides. These nucleotides are what people know as “the letters” or the sequence of the DNA. Since there are 4 natural (technically not correct but never mind) different nucleotides, known sa A,T,C and G, we know the genomic sequence as a series of these 4 letters as they appear in our DNA. What actually these 4 letters mean is not clear to most people but that’s just because it’s not easily understandable unless you’ve taken a molecular biology class. But keeping it simple, they make the coding part of genes, responsible for the creation of all your proteins (almost), essential, of course, for the normal physiological functioning of cells, organs and bodies.

What I want to emphasize in this post is that DNA is far more than the mere sequence of its letters. The coding (or non-coding) sequence of a gene is just the first level of information that DNA can carry. I would characterize DNA as consisting of 3 layers:

The first layer already mentioned is the sequence itself. Linearly chained letters forms the gene that codes for proteins. That, however, is not all: genes include coding and non-coding regions responsible for regulation in the sequence that it’s actually used for the protein. Changing the available sequence to be transcribed (from DNA to RNA) and translated (from RNA to protein) cells can regulate and create variability out of identical genes.

Genes can be expressed differently in many different ways, for example, changing the starting point of transcription or RNA splicing (see “An elegant example of simple rules for complex results – Dscam mRNA alternative splicing“).

The genetic sequence although is not the only regulatory aspect of DNA, actually is just secondary to, what I would call the main switcher, chromatin organization. This is the second layer of information. DNA is not a mere string of its letters but it’s actually wrapped and coiled in intricated ways allowing further regulation from the structural point of view.

chromatin_states_2a
DNA “letters” form the first level. They’re wrapped around histones to form coiled structured that its itself coiled further. The ultimate level of this condensation is in the form of chromosomes (check the featured image of this post).

Tight coiling or loose coiling don’t allow or allow enzymes responsible for transcription and translation to do their jobs. Thus, chromatin condensation is responsible for a big component of gene regulation.

The third level of information, have been getting more and more attention with time. It’s epigenetics. Epigenetics is every characteristic that can be heredited but doesn’t affect the “letter sequence”. Thus, even if the genomic sequence is in principle the same we can have different (even hugely different) outputs (RNA or proteins) depending on epigenetic regulation. This form regulation embeds itself within DNA structure. Many enzyme can alter the DNA molecule (methylation, acetylation ecc..) or the histones (methylation, acetylation ecc..) to alter what can be expressed and what cannot.

Further layers could be added if other aspects are considered. For example I’m aware that the chemical properties of DNA are so outstanding that this molecule is used in a huge variety of researches. For example people use DNA as micro-strings to pull, drag or move particles. They literally play Tug-of-war game with microscopic strings. How cool is that? In such cases, knowing the sequence means little. What’s important is the physical and chemical properties of DNA. And apparently even in this regard, DNA is the champion.

So, in summary, DNA is way more that it’s sequence. This implies that to understand the role of a gene, for example, we can’t just look at its sequence but to a lot more. And this understanding has been complicating research quite a lot. Claiming to understand humans because we completely sequenced his genome, for example, is not only an act of arrogance but also of profound ignorance. DNA is so molecularly complicated that we’re still far away to be able to correlate genes organization with diseases, behaviour or evolution. The fascinating part, however, is realizing how amazingly the DNA machinery is, since, in its evolution, it’s so smartly organized, cleverly functioning and efficient that it’s very hard to grasp. But since DNA is the boss, maybe it should be expected. We have to realize that DNA didn’t evolve only as a sequence of elementary units that together gained a meaning (in the form of proteins) but that those sequences are tightly and hardly organized according to Mother Nature’s blueprints.

Surprised yet? Next time you hear that people can determine your diet from your DNA sequence, think twice, be critical, but also think of how amazing DNA organization is. And in the meantime, let me tell you another story..

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