Re: How do introns exist?

Well, since you know a little about DNA, transcription, and translation, I'll skip that stuff. DNA is the "code" for almost every organism that contains the blueprint for making proteins. In Eukaryotic organisms, DNA is a mosaic of Exons(coding regions of DNA), and Introns(non-coding regions of DNA). So, you're wondering why there are introns if they don't seem to do anything. Well the answer is, they do have a function.

Let's take a step back in time, way back in time to the first arrival of a chemical structure that had the ability to self replicate and catalyze reactions. It is asssumed that RNA was the first genetic code molecule and it could do these functions.

(Check out www.rpi.edu/ ~whittd/COOL/bio.html and hyperion.advanced.org/19926/text/tour/26.htm.) The discovery of what are called Group-I introns, which are RNA molecules that contain two coding regions and a non-coding region in the middle, have lent credence to this hypothesis. It was found that this RNA molecule was able to self-splice that non-coding region out. Once this was done, the spliced RNA molecule is able to catalyze the splicing of other RNA molecules. RNA also had the ability to make copies of itself. So, evolution continued for a couple more million years, and eventually proteins were being made from RNA. Proteins turn out to be better at catalyzing reactions because they are more versatile than RNA due to the 20 different Amino Acids that compose them versus the 4 bases of RNA. More time passes, and DNA arises through reverse transcription of RNA. DNA is more stable than RNA due to it's double helix structure, so eventually it becomes a better template for storing genetic information. That leaves RNA as the message molecule between DNA and Proteins.

Enough of that because we still have to answer why non-coding regions, or introns, exist in the first place. First, it is not beneficial for any system to have all functions performed at once. That takes too much energy, and depletes resources too fast. Early organisms that relied on RNA as not only their source of genetic information, but for performing certain reactions needed a way to regulate what was done, when it was done, and how fast. Introns are a great way to do this. Make it so a molecule has to go through a certain step before it can be used. It lowers the amount of spliced RNA that is available to perform whatever task it does(besides splicing), and thereby slows down whatever comes next. So as the genetic code went from RNA to DNA, introns hung around. Now, as evolution progressed, and new organsims formed, some lost their introns so that rapid growth was achieved. Bacteria for example have no introns, but their genomes are relatively small compared to ours, and therefore easier to replicate. Even though they lack introns, they still have control mechanisms to regulate when genes are turmed on or off. They utilize fouod sources quickly, increase their numbers, and move on.

So why did introns stick around in eukaryotes? Well, we know that splicing of RNA controls the speed at which proteins are made. But introns may also have signals in them that help activate certain regions of DNA for transcription, or enhancer elements. These help make the gene associated with the enhancer more accessible to transcription factors that transcribe RNA.

Also, exons tend ot be discrete domains, or functional units of a protein. For example, antibodies are proteins made by B-cells that are very specific for certain antigens(foreign substances like viral or bacterial proteins). The way antibodies are made to be so specific for different ypes of antigens is by splicing of RNA. An antibody is a Y-shaped protein, with the two arms as the site for binding to foreign molecules. (check out www.cvm.tamu.edu/vtmi409502/immunolo/kabstruc/index.htm) While the stem of the antibody is fairly constant, the arms of the antibody are called variable because the ends are made so that they can bind to a variety of different antigens. The variable region is made by splicing various exons together from RNA. That is what makes our immune system so versatile.

Although antibodies do undergo a type of splicing to generate more than 10^8 different varieties of antigen specific antibodies, this occurs in the DNA of the cell by a mechanism called recombination. Various alleles, or gene variations, for the binding sites of antibodies are brought together to make them specific for a particular antigen. Recombination in general allows for different genes to be brought closer together or farther apart, or in different combinations. This occurs mainly in meiosis to make sperm and egg cells with gene combinations slightly different than somatic cells, but also occurs in immune cells during differentiation. This recombination occurs near the intron-exon junction, sometimes, or can be mediated by sequences within the intron, but the intron is not necessarily excised. Intron excising only really occurs in RNA.

Now, splicing of mRNA will happen when making antibodies. When a B-cell is not activated, it's antibodies are bound to the surface of the cell. However, when an antigen is recognized by that specific B-cell antibody, the cell is activated and a signal is sent to the nucleus that tells it to start splicing the antibody RNA differently. All this does is cause the antibody to be secreted from the cell and not anchored to the membrane. This B-cell is now called a plasma cell.

Last but not least is that since exons code for discrete domains of proteins, these domains can be spliced together in various ways to create new proteins. A kind of evolution on the molecular level. New enzymes can arise that perform new or better catalytic functions. Or new structural proteins may arise allowing for more stability of a cell, or protein coat.

Once quick interesting thing is that not only do almost all viruses (except the T4 bacteriophage) lack introns, but have actually overlapped their genes to save space. Since they are so small, they don't have a lot of room inside their protein coat to pack a lot of DNA, or RNA. So they evolved a space saver for their genetic information. They still do splicing, not to get rid of introns, but to remove other portions of coding regions for a different gene.

I know it is a lot of information, but I think it should really answer you question. There are many things about DNA, and molecular biology we don't understand yet. Nature doesn't always have a logical way of doing things, it just stumbles on ways that work and keeps with them. Good luck and keep asking more questions.

Mark Sullivan