The Physical Structure of the Human Genome

Nuclear DNA Inside each of our cells lies a nucleus, a membrane-bounded region that provides a sanctuary for genetic information. The nucleus contains long strands of DNA that encode this genetic information. A DNA chain is made up of four chemical bases: adenine (A) and guanine (G), which are called purines, and cytosine (C) and thymine (T), referred to as pyrimidines. Each base has a slightly different composition, or combination of oxygen, carbon, nitrogen, and hydrogen. In a DNA chain, every base is attached to a sugar molecule (deoxyribose) and a phosphate molecule, resulting in a nucleic acid or nucleotide. Individual nucleotides are linked through the phosphate group, and it is the precise order, or sequence, of nucleotides that determines the product made from that gene.

Figure 1. The four DNA bases. Each DNA base is made up of the sugar 2'-deoxyribose linked to a phosphate group and one of the four bases depicted above: adenine (top left), cytosine (top right), guanine (bottom left), and thymine (bottom right).

A DNA chain, also called a strand, has a sense of direction, in which one end is chemically different than the other. The so-called 5' end terminates in a 5' phosphate group (-PO4); the 3' end terminates in a 3' hydroxyl group (-OH). This is important because DNA strands are always synthesized in the 5' to 3' direction.

The DNA that constitutes a gene is a double-stranded molecule consisting of two chains running in opposite directions. The chemical nature of the bases in double-stranded DNA creates a slight twisting force that gives DNA its characteristic gently coiled structure, known as the double helix. The two strands are connected to each other by chemical pairing of each base on one strand to a specific partner on the other strand. Adenine (A) pairs with thymine (T), and guanine (G) pairs with cytosine (C). Thus, A-T and G-C base pairs are said to be complementary. This complementary base pairing is what makes DNA a suitable molecule for carrying our genetic information—one strand of DNA can act as a template to direct the synthesis of a complementary strand. In this way, the information in a DNA sequence is readily copied and passed on to the next generation of cells.

Organelle DNA Not all genetic information is found in nuclear DNA. Both plants and animals have an organelle—a "little organ" within the cell— called the mitochondrion. Each mitochondrion has its own set of genes. Plants also have a second organelle, the chloroplast, which also has its own DNA. Cells often have multiple mitochondria, particularly cells requiring lots of energy, such as active muscle cells. This is because mitochondria are responsible for converting the energy stored in macromolecules into a form usable by the cell, namely, the adenosine triphosphate (ATP) molecule. Thus, they are often referred to as the power generators of the cell. Unlike nuclear DNA (the DNA found within the nucleus of a cell), half of which comes from our mother and half from our father, mitochondrial DNA is only inherited from our mother. This is because mitochondria are only found in the female gametes or "eggs" of sexually reproducing animals, not in the male gamete, or sperm. Mitochondrial DNA also does not recombine; there is no shuffling of genes from one generation to the other, as there is with nuclear genes.

Large numbers of mitochondria are found in the tail of sperm, providing them with an engine that generates the energy needed for swimming toward the egg. However, when the sperm enters the egg during fertilization, the tail falls off, taking away the father's mitochondria.