Although researchers made brilliant discoveries that contributed to the understanding of heredity and of evolution before mid-twentieth century, the discovery of DNA–a biological molecule in the shape of a double helix–changed the rate of acquisition of knowledge and understanding of the two pillars of biology to an explosive degree. After a race to see who would be first to publish on DNA, Watson and Crick succeeded: Watson, J.D., and Crick, F.H.C., A Structure for Deoxyribose Nucleic Acid, Nature 171:737-738, 1953. DNA is composed of two chains, strands of nucleotides wrapped around each other in a helical—sort of a spiral staircase—configuration. Each individual nucleotide is composed of three parts: a phosphate group, a deoxyribose sugar, and a nitrogenous base. A covalent bond forms between the phosphate group of one nucleotide and the sugar group of an adjacent nucleotide, resulting in a strong sugar-phosphate frame. Hydrogen bonds form between the nitrogenous bases of two nucleotide chains to form the unique double helix of the DNA molecule. Because hydrogen bonds are much weaker than covalent bonds, the two strands of DNA can unzip from each other relatively easily.
A single DNA chain contains an arrangement of nitrogenous bases: Adenine (A), cytosine (C), guanine (G), and Thymine (T). The bases on one chain form complementary base pairings with the bases on the opposite chain in a single DNA molecule with specific rules governing those pairings. With the discovery of DNA and its function it soon became established that genes are the basic unit of heredity, and they are housed in the DNA structure of every organism. DNA houses an organism’s genome, which is that organism’s complete genetic material. When a cell divides, its DNA must be duplicated in a process called DNA replication so that both resulting cells receive a complete copy of the genome. During replication, the two strands of DNA unwind; each strand then serves as a template for the formation of the new opposite strand, built with near perfect accuracy according to rules of complementary base pairing. If a template strand has an A in one spot, then a T is placed in the opposite strand. Because each DNA molecule consists of one old strand and one new strand, DNA replication is said to be semiconservative.
Assembled human PCNA (PDB ID 1AXC), a sliding DNA clamp protein that is part of the DNA replication complex and serves as a processivity factor for DNA polymerase. The three individual polypeptide chains that make up the trimer are shown. (Photo credit: Wikipedia)
The process of DNA replication occurs in six basic steps: 1. The enzyme helicase unwinds DNA at specific sites along the chain. 2. RNA primers are laid down along the template strand by the enzyme primase. The RNA acts as the starting point for DNA to build on. 3. Elongation begins with the enzyme DNA polymerase adding nucleotides to the end of the growing strand. Elongation proceeds in a different manner in each strand. Nucleotides are added continuously to the leading strand with replication occurring in pieces. 4. The RNA primers are removed and replaced with DNA by the DNA polymerase. 5. The enzyme DNA ligase binds together the fragments of the lagging strand. 6. Chemical proofreading processes take place to remove nucleotide mistakes by DNA polymerases reversing direction. In this post synthesis process, enzymes conduct mismatch repair by scanning the newly formed DNA strand and repairing any errors that are found. It is of significance to note that mutations in mismatch repair genes, which encode the enzymes that proofread and correct errors in DNA, are known to be responsible for certain hereditary forms of cancer. Other mutations may prove to be lethal in and of themselves. Rarely, a mutation is actually beneficial and adds an incremental change which favors survival. Francis Crick went on to establish the process by which DNA produces protein: DNA→RNA→Protein.
Gene expression is the synthesis, or production, of proteins according to the information encoded in DNA. Gene expression is the accumulated phenotypic characteristics, or physical and functional display of a specific genotype. Since proteins determine the structure and function of the cell, gene expression, in effect, controls the cell. Genes are not expressed randomly, or even at equal frequency, within the cell. Instead, the timing and frequency of gene expression is controlled by the individual cell. Many biologists are of the opinion that the differences between humans and chimpanzees arise mainly from differences in gene expression, rather than differences in the genes themselves. The genes of humans and chimpanzees are 98.8% exactly the same and 99% similar, yet the patterns of where and when each gene is expressed in the body are vastly different between the two species. Regulation of gene expression in animals with which we are most familiar occurs at every stage of protein synthesis and is an extremely complex process with multiple sites where mutations can result in profound alterations in function and outcome, most of which are lethal. continued…