Before I get into some more on actually how to break and rejoin the DNA, I wanted to give you some idea about what the whole scale of the problem was. So, just to remind you, I'm going into my owl of many nucleotide sequences. I'm going to withdraw a piece of DNA that is equivalent to the length to the amount of DNA your father gave you when you were conceived. It's about a meter long. Likewise, you have an equivalent amount of DNA from mom, and it's about a meter long. That means that in most of the cells of your body, each one of those cells has 2 meters of DNA that are packed up, rolled up, and stuck into this minuscule five-micron nucleus. So, if I were to actually scale these properly to width, as well as length, they'd only be about 20th of a billionth of a meter in diameter, so you wouldn't be able to see them. When we portray a DNA molecule in a three-dimensional model, that DNA is about 2 nanometers, that is 2 times 10 to the minus 9th meters and we usually do something in the order of, say, 20 centimeters. So that if I had this model here, which is at this width and I scaled it to the appropriate length, it will be something like a billion meters long. So, you can see that when we're doing the representations of DNA, we're going to be forced to make certain kinds of compromises to let you know what's happening. In particular, it's a good idea to remind you that while you might have 2 meters of DNA, only 15 percent of that is genes, and only 3 percent of that is the part of the genes that code for the protein. It's one of the reasons I call DNA administratively top-heavy. It's a molecule that actually, more of it is involved in controlling what's expressed than actually is expressed. If I look at this 3D molecule, I can see I've got the outer backbone. I have the bases on the inside. If you look, you can see I have a major groove. This is where a lot of the proteins come in that grab the DNA and control them. Those proteins are coded for by other parts of the genome. So, you can see that not only is the majority of the genome, basically, sequences that are there to control the expression of proteins, it turns out, at least in humans, that a majority of the proteins in there are there to control the production of other proteins. So, it's really quite an interesting system. When we get into the final production of an antibody, we will see that the gene that codes for it has a lot of different sequences on it that are there for control. Now, that's true if a lot of your genes are in the genome and one of the things that gives you the flexibility to develop into the marvelous person you are is that your genome may only have the instructions for 20,000 genes. But when they make messages from these things, they mix them up in such a way that they make many more different proteins than that. What happens when an antibody is even more complex, because we will not only mix up instructions in the messages, we will also mix up instructions in the DNA. Now, here's why this is going to be such an interesting problem. This is a double helix. I have to unwind it to do anything with it. Well, if I just want to copy part of it, I can unwind part of it, copy that, and put it back together. On the other hand, if I want to copy the whole thing, that is if I have a cell and it's dividing, then I have to unwrap the whole thing and you can see this makes a real mess to open this. So, we have a lot of problems in using the DNA, in copying the DNA, in copying from the DNA that come strictly from the way this molecule is designed as a double helix. Now, here's some other view of DNA you don't usually get. I'm going to pick this up and I'm going to put it into the camera. I'm hoping you can see that now you see a circle. Here's an end-on view of the DNA molecule. I'm going to count around the bases in this model and see how many it takes to make a full turn. One, two, three, four. Now, if you'll notice, this piece up here is the other complimentary strand and it's going to kind of get in our way and make it hard to see. Five, six, seven and at this point, things are getting very messy and you may just have to take my word for it that the next ones are, of course, eight, nine, 10 and 10 is a little bit short of one, and it turns out that it takes 10 and a half bases to get around, make a full turn on a DNA molecule. So, if we are looking at what it takes essentially to configure a one-turn sequence, that sequence is 12 nucleotides in length and we will see that if we go around the outside of that sequence, we're going to make just over one turn. That'll be one turn with this little bit of overlap over here; 12 bases, a little bit of overlap. If we have a two-turn sequence, it's going to make a second turnaround and that second turnaround will have another 11 bases for a total of 23. If we have a two-turn sequence, we'll have another turn plus a little smidge, half-base in length extra. This will provide us with two very defined shapes, cylindrical shapes, easily recognized by a multi-enzyme complex. This turns out to be very important in looking at how you put together sequences when you're rearranging the gene. That is we will have controlling sequences, some of which have 12 nucleotides or a one-turn sequence, others of which will have 23, and will be two-turn. So, we always have to put a two-turn with a one-turn. When I say putting a two-turn with a one-turn, that is what I am talking about. Okay. So, I have given you all of this sort of DNA and I told you how much is there and we have all of this DNA that's not only coding for amino acids, but also coding for control. I want to particularly take up the very special case of what makes adaptive immunity adaptive. When we look at the genes for the immunoglobulin receptors or antibodies, they're basically the same genes and later in the second part of the course, we will look at the genes for the T-cell receptors. In both cases, we're going to have large-complex genes that we're going to mix and match. To do that, we're going to break and rejoin DNA, but this is going to give us an option we don't have with any other system. We can use a relatively small amount, relatively, to produce what I refer to as a vast number of combinations, possibilities, and different forms of adaptive molecules. So, if I look at the DNA here, I have 2 meters. If I add up all of the DNA that makes up the genes that code for adaptive parts of this system, I'm going to find that it's about 2 percent of the whole genome. That is about 1 millimeter from your mom, 1 millimeter from your dad, will contain all the DNA you need to make an endless supply of different recognition molecules. Then, they're scattered on different chromosomes. We're going to see that the light chain genes are on two different chromosomes.The heavy chain gene is on another one; 2, 22, 14. TCR genes are on different chromosomes. But, again, a reminder that you will have one gene of each one of these from mom, one of each one of these from dad. So, you're going to get two different copies of every single thing that we talk about and that's going to give you two tries per gene to make something that works. Now, another just sort of kind of fun reminder. This 1 percent of the DNA makes up about 3,000 kilobases and that's actually in the ballpark of a whole E. coli genome. So, while it's a small part of your genome and actual bacterium doesn't have that much more DNA per cell in order to code for all of its enzymes. Another thing that's rather interesting is that if I compare the E. coli to your mitochondrial genome, I will see that the E. coli is much, much bigger. Your mitochondrial genome only has about 17 kilobases. So, that's a much smaller piece of DNA. So, just as a kind of scalar reminder, I wanted to draw a ribosome. So, here is the large sub-unit of the ribosome. Here, I'm going to kind of do the small sub-unit. They're kind of fit together and this whole structure is in the order of 250. Let's just round it to 30 millimicrons or nanometers. So, that would be 30, and that would really be nanometers. It's the same thing as 10 to the minus 9th meters. If I put an antibody on top of the ribosome for scale, it's going to look kind of like this. I do have a picture of this in your outline. Okay. So, this thing tends to be in the general vicinity of about 10 nanometers, 10 millimicrons, 10 to the minus 9th meters. So, a DNA molecule, if I put it in there, would be kind of like- what would be fun? This is a cute color. It would again be much narrower like that. But, of course, if I put the whole scale, it would go on forever. Now, if I wanted to put this in another context and say, put a whole mitochondrion around it, that would fill up the blackboard and more. So, you can see that when we're looking at DNA antibodies and ultimately, protein synthesis with our mitochondria, we're looking at some very small-scale structures. The ability to kind of perceive the levels of scale in the universe is something that's kind of mind-boggling. One thing I would like to recommend to you is that the Eameses put together a movie, a video called "Powers of Ten." These are the same guys that invented the Eames chair. They were really very artistic and wonderful people. They started out with a picture one meter above a picnicking couple. Then, they went up by to 10 meters, 100 meters, 1,000 meters, you went up into the universe then, you went back down and you went in and you looked at the couple at 10 centimeters, and on up, and they went down into corks. So, that is actually up right now on YouTube and I've given you a link to that. So, if you're having a little bit of trouble kind of perceiving the vastness of the scale in terms of how tiny it is to up the things that are really, really huge, I highly recommend the Eames video, "Powers of Ten."
