The discovery of the structure of DNA is one of the most important scientific breakthroughs in the last century. It was important enough to get James Watson and Francis Crick, the discoverers of this nucleic acid's shape, the Nobel Prize for physiology/ medicine in 1962. What is so important about DNA? Why are scientists trying to figure out all 6 billion letters of it, and how does it affect me personally? These are all important questions, but to get these answers you first must know a little bit about what DNA is.
A rotating model of DNA. Created for you by the Gattaga Team.
The discovery of the structure of DNA is one of the most important scientific breakthroughs in the last century. It was important enough to get James Watson and Francis Crick, the discoverers of this nucleic acid’s shape, the Nobel Prize for physiology / medicine in 1962. (WGBH, 1998, para. 8) What is so important about DNA? Why are scientists trying to figure out all 6 billion letters of it, and how does it affect each of us personally? These are all important questions, but to get these answers you first must know a little bit about what DNA is.
DNA stands for deoxyribonucleic acid and is found in every human cell on the face of the planet. Considering that there are about 80 trillion cells in an adult human, you might be thinking, “How could I not have heard more about something so big?” (Mack, 2001, para. 4). But then think about this: not only is DNA in every human cell, it’s in every cell of every living thing in the world including animals, plants, and bacteria! However, there aren’t the same amounts of DNA in each cell. In a human cell, there are about 6 billion base pairs that stretch out to be about 6 meters of DNA per cell, 300,000 times greater than the diameter of the cell. In bacteria cells though, there are only about 6 million base pairs. As demonstrated above, you might conclude that the more base pairs DNA has, the more complex the organism. But what exactly is a base pair, and how can it affect the complexity of an organism?
DNA is comprised of genes; sections of DNA that code for polypeptide chains(proteins) on a one-to-one ratio(insert link for polypeptide chain). A gene is the basic unit of inheritance, or the system by which organisms create offspring, and it is comprised of nucleotides. One nucleotide consists of one organic nitrogenous base, one five-carbon (5-C) sugar, and one phosphate group. The nitrogenous base and a pentose sugar together is called a nucleoside. Combined with a phosphate group, the nucleoside becomes nucleoside monophosphate, or what is more commonly referred to as a nucleotide. In DNA, the pentose sugar is always deoxyribose and the phosphate group is always one phosphate molecule bonding with four oxygen molecules. It is the variance in the nitrogenous base that allows DNA to be so powerful and so influential in the development of life.
The four DNA nitrogenous bases fall into two categories. The pyrimidines, which are the smaller of the two, have a ring of six carbon molecules. The larger group, the purines, each has the six carbon structure as well as a five carbon ring fused onto it. Of the four bases found in DNA, cytosine and thymine are pyrimidines while adenine and guanine are purines. Because of the shapes of these bases, adenine can only form a hydrogen bond with thymine to make a base pair, while guanine can only hook up with cytosine. A hydrogen bond is when that the positively charged hydrogen atom in one base is attracted to a negatively charged atom in the other base.
This A-T/G-C pairing is very important in the function of DNA, but we are still missing a fundamental piece in the actual structure of DNA.
In addition, DNA is packed into separate chromosomes, which are long strands of DNA coiled with some additional protein molecules. So how does knowing the physical structure of DNA help understand this fantastically shaped biochemical molecule? Read on and learn for yourself.
Interactive DNA Diagram. Created for you by the Gattaga Team.
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As you already know, DNA is found in every cell in the human body. But how does DNA get into the new cells that your body is constantly making to replace the old ones? This is where the structure of DNA comes into play. As the cell is dividing, an enzyme called DNA polymerase elongates the DNA in the cell while another enzyme, helicase, causes it to unwind from its helical shape. The constantly moving point at which polymerase unzips DNA is called the replication fork. Enzymes in general are proteins that speed up a chemical reaction and allow it to occur with less activation energy, while not being used up in the reaction. DNA polymerase is specifically designed to elongate the DNA strands in addition to adding the nucleotides to the new DNA strand. In humans, this elongation takes place at about 50 nucleotides per second, while in bacteria the speed is almost 500. Once unzipped, each single strand of DNA becomes half of a new piece of DNA. Due to the fact that only adenine can bond with thymine and cytosine can bond only with guanine, each strand’s new half is already pre-determined and will look exactly like one it just unzipped from! In this manner, DNA is preserved from cell to cell without any changes to the actual information that DNA codes for.
Though the idea is simple, the method of making a new DNA strand from a pair of old ones is quite complex. DNA replication itself starts at a point on the DNA strand called the origin of replication. This is a specific sequence of base pairs that DNA polymerase recognizes and latches on to, sparking the chain of events that copies DNA. This is when the two different strands of DNA running in opposite directions comes into play. Each of the five carbons on a nucleotides deoxyribose sugar are labeled from 1’ to 5’ with 3’ and 5’ facing in opposite directions. Thus, the 5’ end of one DNA strand is next to the 3’ on the other one when the strands are in helical form (and vica versa). This is important to DNA polymerase because it can only replicate DNA in the 5’ to 3’ direction. Thus, as DNA is replicated there is always one side that is replicated continuously with the movement of the replication fork, called the leading strand, and one side that is replicated in pieces in the direction opposite the replication fork, called the lagging strand. The lagging strand, which is half of every replicated DNA helix, gives rise to a problem with this method of DNA replication.
The lagging strand is replicated in strands, called Okazaki fragments (100-200 nucleotides long), while the enzyme DNA ligase is attaching the newly made strands together. However, DNA polymerase can only add nucleotides to an existing strand; it can’t start a strand by itself. An enzyme called primase puts together a small single strand of RNA, a nucleic acid similar to DNA, for polymerase to start adding to. This small RNA strand, about 10 nucleotides long in humans, is called a primer. In the leading strand, the primer is only needed to start the replication process and DNA polymerase later replaces the RNA primer with an equivalent DNA strand. In the lagging strand, however, a primer is needed every time a new fragment is started. Polymerase then has yet another job to do: it must replace the RNA at the beginning of each strand before ligase can connect it with the strand in front of it. Surprisingly, the use of the primer in this system of replication creates another problem that is indirectly the source of something we all must face: old age.
Click to enlarge. Overview of DNA replcation.
Each time the RNA primer is used on a new chain ready to be replicated it is ‘deleted’ and replaced by the corresponding DNA sequence. However, the point of the primer is to give the DNA polymerase a place to start at because it can’t start a chain and it can only add to a chain on its 3’ side. So what happens when the primer is removed at the start of the chain on the 5’ end? The polymerase can’t get to where it needs to go to add that section back on. Thus, in multi-cellular organisms’ replication, each daughter strand gets shorter and shorter as more replications occur (single-celled organisms have circular shaped DNA to solve this problem). What is the significance of this fact? Well, it has been shown that DNA is shorter in cells that come from older people and in cells that have divided many times. Perhaps you can see the correlation now: it is possible that the DNA erosion in cells that comes about from regular replication may cause old age.
However, nature has also provided a solution to the problem of ageing in the germ cell lines and in gametes, the cells in humans used to produce offspring. Both these types of cells, given everything they need, are believed to live forever. All eukaryotic cells have telomeres at the ends of their DNA strands. Instead of eroding the genetic material, replication erodes these repetitions of a nucleotide sequence, typically TTAGGG in humans. In germ cell lines and gametes, the enzyme telomerase speeds up the lengthening of the telomeres which quickly regain their original length from before replication. Telemorase isn’t in the body’s somatic cells, or regular body cells, only in gametes and germ cell lines. Interestingly, scientists have also found telomorase in somatic cancerous cells, which may explain their incredible lifespan. The implications of such biotechnological research are apparent: not only could telomere mapping find a cure for cancer, it could solve the problem of aging altogether.
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