The case of "junk DNA" and why it shouldn't be called junk: Topology.

  
(This is part 4 of 4 in a series dedicated to the concept of "junk DNA". Links to the previous parts: Part 1, Part 2, and Part 3).

This is DNA:

This is also DNA:

Image from Wikimedia Commons

 The point I'm making: we often think of DNA as a code, a string of four letters repeated over and over again. Yet DNA is so much more than that. DNA is a three-dimensional structure, and as such it has a topology. In biology, the way molecules fold and spread into space is just as important as their chemical composition. The HIV virus, for example, can escape antibodies thanks to the way it hides its "docking" sites: as a consequence, the antibodies "bounce off" its surface and are unable to "grab" it. Some changes in the way certain proteins fold can change their functionality.

Which brings me back to "junk" DNA. I have already mentioned how several disease association studies (studies that look at which particular sites in the DNA increase the chance of getting a certain disease) have found significant correlations with mutations in the non-coding part of the genome. This may seem surprising since once the DNA is spliced, all the non-coding bits are thrown away. So, technically, those mutations should have no bearing on our biology.

Last time I discussed how a possible explanation lies in epigenetics, the mechanisms that activates pseudogenes that would otherwise be non-coding. If a pseduogene has a "defective" mutation and it gets "turned on" (and thus it becomes a coding gene), then the mutation will affect the individual's chance of expressing the disease trait.

Today I want to talk about another possible explanation. The mutation may never become a coding one, but it may very well change the topology of the chromosome where it sits. And some changes in topology may indeed affect our phenotype or, in other words, our biology.

As you know, our DNA is packaged in 23 pairs of chromosomes. DNA needs to be "un-packaged" so that the information can be read. This process, called transcription, is done through an enzyme called RNA polymerase. The enzyme "links" the chromosome and "unwinds" the DNA so that it can turn into RNA. Here's a nice animation of how the process works:

You can see how the topological structure of the chromosome plays an important role: a mutation that changes the architecture of the chromosome may very well affect the way the RNA polymerase enzyme attaches to it, which, in turn, may result in a defective transcription. Think of a pesky piece of torn plastic bag jamming your duffel's zipper. Ugh. Not good. The zipper may jam or it may skip some teeth, some nucleotide bases that won't be read, resulting in the wrong information. And wrong information often translates into defective proteins and defective proteins may results in diseases. Or, it may result in some advantageous trait. The original mutation is indeed in the "junk DNA," but it ends up being no junk at all.

In summary:

• The vast majority of our DNA is non-coding, meaning that it gets thrown away after transcription and hence is not translated into proteins.
• Most of the information contained in this part of the genome is redundant: many of our genes are repeated over and over again, but often the copies are "turned off."
• This redundancy is what allows Mother Nature to "fix" potential mistakes, but also to find new evolutionary escapes.
• The non-coding part of the DNA doesn't remain non-coding throughout our lifetime. Traumas and stress and other life changes can activate or deactivate certain genes.
• Even though the non-coding part of the genome has no bearing in the making of proteins, it can change the 3-dimensional structure of the DNA and still affect the biological processes taking place in the body.

It's true that the term "junk DNA" has now become historical, and the more we learn about this mysterious part of our genome, the less likely we are to take the term literally. Still, it has led to many misconceptions. Like all new concepts, it takes a while to grasp its importance and understand it. It reminds me of a quote from population geneticist J.B. Haldane:

"Theories have four stages of acceptance:
        i. this is worthless nonsense,
        ii. this is interesting, but perverse,
        iii. this is true, but quite unimportant,
        iv. I always said so."

Picture: White anemone, Seattle Aquarium. Canon 40D, focal length 85mm, exposure time 1/5.