Tuesday, August 3, 2010

Introduction to DNA and its properties

What is DNA?

The work of many scientists paved the way for the exploration of DNA. Way back in 1868, almost a century before the Nobel Prize was awarded to Watson, Crick and Wilkins, a young Swiss physician named Friedrich Miescher, isolated something no one had ever seen before from the nuclei of cells. He called the compound "nuclein." This is today called nucleic acid, the "NA" in DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). DNA is the hereditary material in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus, but a small amount of DNA can also be found in the mitochondria. DNA, along with the instructions it contains, is passed from adult organisms to their offspring during reproduction.
Properties

DNA is a double-stranded molecule that is twisted into a helix like a spiral staircase. It is made of chemical building blocks called nucleotides. These building blocks are made of three parts: a phosphate group, a sugar group and one of four types of nitrogen bases. A different nitrogenous base leads to the formation of the different forms of nucleotides such as Adenine(A), Thymine(T), Cytosine(C) and Guanine(G). The order, or sequence, of these bases determines what biological instructions are contained in a strand of DNA. For example, the sequence ATCGTT might instruct for blue eyes, while ATCGCT might instruct for brown. To form a strand of DNA, nucleotides are linked into chains, with the phosphate and sugar groups alternating.



Nitrogenous Bases

The nitrogenous bases are rather complex single or double ring structures containing nitrogen and are attached to the carbon of the sugar. Nitrogenous bases are of two types based on the number of rings. The Four Nitrogenous Bases in DNA are Adenine(A), Guanine(G), Cytosine(C), and Thymine(T). Adenine and guanine are also known as purine bases; they are double ringed nitrogenous bases which are linked to sugar by using nitrogen present at 9' -position. Cytosine and thymine are also called pyrimidine bases; they are single ringed nitrogen bases which are linked to sugar by using nitrogen present at 1 ' -position. Each deoxyribonucleotide will contain one of these four bases.


Base pairing 

Chemical structure of DNA. Hydrogen bonds shown as dotted lines.
Each type of base on one strand forms a bond with a specific base on the other strand. This is called complementary base pairing. In order to stabilize the double helix bonds, hydrogen bonds are made between two parrallel nucleotides of specific type, such as Adenine with Thymine and Cytosine with Guanine.  

As hydrogen bonds are not covalent, they can be easily broken down, therefore be pulled apart, either by a mechanical force or high temperature. As a result of this complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. The specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms, by determining the specific characteristics or phenotypes of the organism.
An AT base pair with two hydrogen bonds, and a GC base pair with three hydrogen bonds.

The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figure above). DNA with high GC-content is more stable than DNA with low GC-content, but contrary to popular belief, this is not due to the extra hydrogen bond of a GC base pair but rather the contribution of stacking interactions.(This is because the hydrogen bonding merely provides specificity of the pairing, not stability) As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determine the strength of the association between the two strands of DNA. Long DNA helices with a high GC content have stronger-interacting strands, while short helices with high AT content have weaker-interacting strands. In biology, parts of the DNA double helix that need to separate easily tend to have a high AT content, making the strands easier to pull apart. In the laboratory, the strength of this interaction can be measured by finding the temperature required to break the hydrogen bonds. When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single common shape, but some conformations are more stable than others.


Sugar-Phosphate Backbone


The sugar-phosphate backbone, as its name implies, is the major structural component of the DNA molecule. The backbone is constructed from alternating ribose sugar and phosphate molecules which are highly polar. Because the backbone is polar, it is hydrophillic which means that it likes to be immersed in water.


That DNA is antiparallel means that the two strands of DNA have opposite chemical polarity, or, stated in another way, their sugar-phosphate backbones run in opposite directions. Direction in nucleic acids is specified by referring to the carbons of the ribose ring in the sugar-phosphate backbone of DNA. 

 
 The full name of DNA, deoxyribonucleic acid, tells you the name of the sugar present - deoxyribose. Deoxyribose is a modified form of another sugar cqlled ribose. As its name suggests, Deoxyribose is ribose which has lost an oxygen atom - "de-oxy". Deoxyribose is a pentose sugan as it has 5 carbon atoms. 

The phosphate group is bonded to the 5' carbon atom of one deoxyribose and is covalently bonded to the 3' carbon of the next. The phosphate group is polar and therefore capable of interacting with water molecules. This makes the sugar-phosphate backbone hydrophillic. 

The sugar-phosphate backbone of DNA is formed by phosphodiester bonds, a covalent chemical bond between two sugar groups and a phosphate group.

  The interior portion of DNA, the bases, are relatively non-polar and therefore hydrophobic.  This duality has a very stabilizing effect on the overall structure of the DNA double helix: the hydrophobic core of the DNA molecule 'wants' to be hidden inside the sugar-phosphate backbone which acts to isolate it from the polar water molecules.  Due to these hydrostatic forces there is a strong pressure gluing the two strands of DNA together.


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