0.1 Genetics background

The most naive picture of the eukaryotic genome is a long string of linear DNA balled up somewhere inside the cell. This formulation fails on several important grounds: first, although DNA is a linear molecule, it is not necessarily accessed in a linear fashion; second, DNA has a very significant secondary structure, it is not simply balled up at random; and third because DNA does not act in isolation, it is immersed in the context of the cell's nucleus where numerous proteins and epigenetic processes interact with the DNA to regulate gene expression.

Let's begin by discussing the in vivo structure of DNA in a typical eukaryotic cell. A molecule of DNA is composed of two antiparallel and complimentary strands of deoxyribonucleicacid. Antiparallel means that the two strands have opposite chemical polarity, or, stated 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 (ribose is a sugar) in the sugar-phosphate backbone of DNA. 5' specifies the the 5th carbon in the ribose ring, counting clockwise from the oxygen molecule, and 3' specifies the 3rd carbon in the ring. Direction of, and in reference to, DNA molecules is then specified relative to these carbons. For example, transcription, the act of transcribing DNA to RNA for eventual expression, always occurs in the 5' to 3' direction. Nucleic acid polymerization cannot occur in the opposite direction, 3' to 5', because of the difference in chemical properties between the 5' methyl group and the 3' ring-carbon with an attached hydroxyl group.

The basic structure of DNA can be divided into two portions: the external sugar-phosphate backbone, and the internal bases. The sugar-phosphate backbone, as its name implies, is the major structural component of the DNA molecule. It is the external portion of the DNA molecule because it is highly polar, and thus hydrophillic (meaning it likes to be immersed in water). Correspondingly, the interior bases of the DNA molecule are non-polar and 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; thus there is a strong hydrophobic pressure gluing two molecules of DNA together.

There are four bases in DNA: adenine (A), guanine (G), thymine (T), and cytosine (C). In RNA uracil (U) is found in place of thymine (T). Inside a DNA molecule these bases pair up, A to T and C to G, forming hydrogen bonds that further serve to stabilize the DNA molecule. Because the interior bases pair up in this manner, we say the DNA double helix is complimentary. It is the sequence of these bases inside the DNA molecule that we refer to as the genetic code.