DNA
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[edit] Introduction
Deoxyribonucleic acid (abbreviated to DNA) is the molecular structure which provides the genetic instructions for the function of a cell. In this article, we provide an introduction to the structure of DNA and its role in the cell.
[edit] Chemical structure of DNA
Nucleotides can be stuck together in two ways. First, the phosphate of any nucleotide can attach to the sugar of any nucleotide, with their bases dangling off to one side. When we join two nucleotides like this, obviously one of them still has a phosphate free to attach to the sugar of another nucleotide, and the other has a sugar to which the phosphate of a further nucleotide can be attached, which means that you can then add on another nucleotide by attaching it to one end or the other, and, indeed, you can make a chain of nucleotides any length you like by sticking them end to end, sugar-to-phosphate, in this way.
The "phosphate" end of such a chain is called the 5´ end and the "sugar" end is called the 3´ end. You will notice that it would be perfectly possible to join the 5´ end to the 3´ end and get a loop: indeed, in bacteria DNA does come in loops.
Note that because the bases play no part in this way of sticking nucleotides together, the four bases can appear in any order along the phosphate-sugar "backbone" of this molecule.
The second way to stick nucleotides together is base-to-base. These base-pairings are specific: that is, adenine will stick to thymine and only thymine; thymine will stick to adenine and only adenine; cytosine will stick to guanine and only guanine; guanine will stick to cytosine and only cytosine.
This means that we can stick together two chains of nucleotides base-to-base, so long as the chains are complementary: that is, where one has adenine, the other has thymine, and where one has guanine, the other has cytosine, as shown in the diagram. Note that because of the way the bases fit together, the two strands are antiparallel: the 5´ end of one is next to the 3´ end of the other.
Because the bonds between bases are hydrogen bonds, they are fairly weak and easy to break, making it quite easy to "unzip" DNA into its two complementary strands.
To understand the significance of DNA in genetics, it is not necessary, after all, to remember whether adenine is a purine or a pyrimidine, or how many hydrogen bonds guanine forms with cytosine, and suchlike stuff. For almost all purposes, the diagram to the right tells you all you need to know about the structure of DNA:
- Because we can go on chaining together the sugar and phosphate parts of nucleotides indefinitely, a molecule of DNA can be any length.
- Only certain bases can pair together between the strands: A with T and G with C. Because of the base-pairing rule, the two stands are complementary, and so a list of the bases along one strand allows us to know exactly what the other strand looks like.
- Because the sugar and phosphate parts of each nucleotide are identical and so all fit together the same way, the bases along any strand can consist of any string of A, T, G, and C. The other strand then has to have T where the first strand has A, G where it has C, and so on, because of the base-pairing rule.
[edit] Replication
As Crick and Watson observed in their classic paper on the structure of DNA:
- It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material. (Crick and Watson, A Structure For Deoxyribonucleic Acid[1])
For clearly, if we unzip the two strands of the DNA, and then make each one double-stranded again by adding nucleotides to each strand according to the base-pairing rules, then because of the specificity of the base-pairing rules (i.e. the fact that T will only go with A, and C with G) it follows that the two new lengths of double-stranded DNA will both be identical with each other and with the DNA you started with.
By this means, new copies of the DNA can be made when cell division takes place, so that the two new cells both have a copy of the DNA contained in the parent cell; and in the same way, copies of DNA can be made during meiosis, to be passed on in sperm or eggs, so passing genetic information down from generation to generation.
In our diagram, we have not indicated the mechanism by which the cell goes about unzipping the two strands and complementing them. This process is more complicated and interesting than you would think, and will be covered in a separate article.
[edit] Transcription
In order for DNA to control what goes on in the cell, the information represented by the sequence of bases in the DNA must undergo transcription into ribonucleic acid (RNA). To explain this process, we first require a brief review of what RNA is.
[edit] RNA
Like DNA, RNA is made by stringing together nucleotides, by connecting their sugar ends to their phosphate ends. The differences between RNA and DNA may be summarised as follows:
- RNA uses a different sugar from DNA: ribose rather than deoxyribose, which is why it is called RNA (ribonucleic acid) rather than DNA (deoxyribonucleic acid). As far as we shall be concerned, for the purposes of this article, the identity of the sugar really makes no difference.
- The four bases of DNA are adenine, cytosine, guanine, and thymine, but the four bases of RNA are adenine, cytosine, guanine, and uracil. Uracil is very similar chemically to thymine, and like thymine it will bond with adenine.
- RNA usually comes in a single strand. (It can form a double strand just like DNA, and does in some viruses, but all the RNA we shall need to discuss in this article forms single strands.)
- Because RNA comes in a single strand, sections of it can bond with itself by the pairing of complementary bases to make structures that are much more interesting than DNA's regular double helix, and which because of their shape can take an active part in the metabolism of the cell.
[edit] DNA to RNA
RNA is so like DNA that it is easy to see, in principle, how a strand of DNA may be copied into RNA. We can unzip the section of DNA that we want to copy, and attach the ribonucleotides that make up RNA to the anticoding strand: (that is, the strand of DNA opposite the one we want to copy) so as to make a strand of RNA. Because of the base-pairing rules, this strand will have the same bases as the one we want to copy (the coding strand), except that RNA uses the base uracil where DNA uses the base thymine. The table below shows the relationship between the coding strand, the anticoding strand, and the transcribed RNA.
| Strand of DNA to be copied ("coding strand") | A | C | G | T |
| Opposite strand ("anticoding strand") | T | G | C | A |
| Transcribed RNA | A | C | G | U |
This is carried out in the cell by an enzyme called RNA polymerase. We shall now look at what it does in somewhat more detail.
RNA polymerase latches on to a double strand of DNA anywhere it finds a sequence of bases known as a promotor: special sequences of bases that, in effect, tell the RNA polymerase "Start transcribing here". The RNA polymerase unzips the DNA that comes after the promotor and starts stringing together ribonucleotides along the anticoding strand to make a strand of RNA. (The RNA polymerase can determine which is the coding strand and which the anticoding strand because the coding strand has the promotor on it.)
The RNA polymerase moves down the anticoding strand in the 3´ → 5´ direction, unzipping the DNA as it goes, and complementing the anticoding strand with RNA. It also zips the two strands of DNA back up behind it as it goes: in order to do this, of course, it must cast loose the RNA from the anticoding strand, so that the two strands of DNA can be zipped back together; so the RNA is only attached to the anticoding strand just long enough to make sure that their bases are complementary: the rest of the strand of RNA dangles free behind the RNA polymerase.
The RNA polymerase stops transcribing when it reaches a terminator (a sequence of bases that tell the RNA polymerase to stop transcribing). The RNA polymerase then releases the DNA and the RNA.
There will be a lot of promotor and terminator sequence on a piece of DNA: the regions between them, that get transcribed by RNA polymerase, usually correspond to our concept of a gene. These will be transcribed separately by different bits of RNA polymerase working on different sections of the DNA.
After transcription (and possibly some editing) two things can happen to the RNA. As we noted above, a strand of RNA can stick to itself, by the pairing of complementary bases, so as to curl up into a molecule with an interesting shape and interesting chemical properties: such pieces of RNA can go on to play a direct role in the functioning of the cell. An example is given in the diagram to the right, which shows a molecule of transfer RNA (tRNA).
Most of the RNA produced in transcription, however, will be messenger RNA, (mRNA) which undergoes a further process, translation, which will be the subject of the next section.
[edit] Translation
Translation is a process by which the sequence of bases in messenger RNA (mRNA) directs the synthesis of polypeptides (the strings of amino acids that make up proteins).
We would draw attention to a couple of points. First, DNA is not involved in this process: all DNA does is get replicated or transcribed into RNA. Second, we have still included the process of translation in this article on DNA. The reason that we include it is that while the process of synthesising polypeptides is controlled by RNA, the RNA is a transcript of DNA: so really the DNA is controlling polypeptide synthesis, at one remove, by remote control.
[edit] Amino acids, polypeptides, and proteins
For the purposes of this article, it is sufficient to think of an amino acid as having a "head", a "tail", and a bit sticking out at the side (the side chain). These amino acids can be joined together head to tail to form a polymer, with their side chains dangling out to one side. Such a chain of amino acids is called a polypeptide.
So far, this sound a lot like RNA or DNA (although we should mention that sugars and phosphates are not involved in the "heads" and "tails" of amino acids: the underlying chemistry is quite different). However, the polypeptides don't do anything as simple as base-pairing with their side chains: their chemistry is more complicated than that, and it is a difficult problem, involving a lot of computer time, to figure out the shape that a polypeptide will curl into given the sequence of amino acids it's made of. Another difference is that whereas there are only four bases in DNA or RNA, polypeptides are made of a combination of up to 20 different kinds of amino acid.
The polypeptides combine to form proteins (or some proteins consist of just one polypeptide). Proteins, to put it in the simplest possible terms, are what make a cell tick: with the exception of the functional RNA that we have mentioned above, the chemicals in the cell that are not proteins are fairly inert molecules on which the proteins act: building materials, as it were, that proteins use to build and maintain the cell.
[edit] RNA to polypeptides
As we have explained above, most transcribed RNA is messenger RNA (mRNA) which contains instructions for making a polypeptide. The manufacture of polypeptides is carried out by a part of the cellular machinery called a ribosome. The ribosome works its way along a piece of mRNA from the 5' end to the 3' end, and, according to the sequence of nucleotides it encounters along the mRNA, attaches amino acids to a polypeptide chain.
You will recall that there are only four bases, whereas there are twenty amino acids. Four bases can code for twenty amino acids because the ribosome "reads" the bases three at a time: such a group of three bases is known as a triplet or codon. So, for example, when it "reads" the bases CAG, it tacks the amino acid glutamine onto the end of the polypeptide it's making, and moves three bases further down towards the 3' end of the mRNA, , where it may, for example, encounter the bases GUA, in which case it will tack the amino acid valine onto the end of the polypeptide it's making, and moves three bases further down towards the 3' end of the mRNA ... and so forth.
The relationship between codons and amino acids, which assigns glutamine to CAG, and valine to GUA, and so forth, is known as the genetic code. You will notice that there are 4 × 4 × 4 = 64 different possible codons, and only 20 amino acids. In fact, the genetic code exhibits redundancy: that is, more than one codon can code for the same amino acid. For example, CGU, CGA, CGT, CGC, AGG and AGA all code for arginine. Also there are three codons (UAA, UAG, and UGA) that don't code for any amino acid, but rather are "stop" codons: they tell the ribosome to finish making the polypeptide. The codon AUG also doubles up as a "start" codon: besides coding for methionine, the first occurrence of AUG on the strand of mRNA tells the ribosome where to start transcribing codons into amino acids.
Further details and discussion of translation and the genetic code will be found in our main article on the Genetic Code.
[edit] Chromosomes
In cells, DNA is organised into structures called chromosomes, each consisting of one long string of DNA (or, in the case of bacteria, a loop of DNA) packaged in proteins. The number of chromosomes per cell varies from species to species: in humans there are 46.
In sexually reproducing organisms, chromosomes, (except for sex chromosomes) come in homologous pairs: that is, a pair of chromosomes which have the same genes on each of them, but possibly with slight variations.
For a more detailed look at the function of chromosomes in cell division and in reproduction, see our article on Chromosomes.
[edit] DNA and Mendelian genetics
We are now in a position to relate the concept of a gene in DNA to the fundamental concept of a gene in Mendelian genetics. A gene is a stretch of DNA which codes either (occasionally) for a piece of functional RNA, or (usually) for a polypeptide.
Genes control characters of the organism because the sequence in the DNA determines the sequence of the mRNA, which determines the sequence of amino acids strung together by the ribosomes, which determines the shapes and chemical properties of the polypeptides, which stick together to make proteins, which make the cell work.
The reason that Mendel found that organisms have two of each gene is simply that the homologous chromosomes come in pairs; and the different alleles of genes, in Mendelian genetics, correspond to slightly different sequences of DNA coding for polypeptides with different sequences of amino acids, and which therefore have different effects on the metabolism of the cell.
