alt="c03i002"/> TABLE 3.1. Numbers of predicted protein‐coding genes in various organisms.
| Organism | Number of predicted genes |
|---|---|
| Bacterium – Escherichia coli | 4288 |
| Yeast – Saccharomyces cerevisiae | 6091 |
| Fruit fly – Drosophila melanogaster | 14 133 |
| Worm – Caenorhabdites elegans | 19 735 |
| Plant – Arabidopsis thaliana | 27 029 |
| Human – Homo sapiens | 19 116 |
Medical Relevance 3.1 Anti‐Viral Drugs for HIV
It is hard to find drugs that will inhibit replication of the HIV virus, which causes the disease AIDS, without damaging the host cell because the HIV virus uses the host cell's synthetic machinery. However, the first act of the virus is to make DNA from its RNA genome using an enzyme contained within its viral envelope, called reverse transcriptase. Azidothymidine (AZT), the most widely used anti‐AIDS drug, inhibits this enzyme.
In a normal interphase cell about 10% of the chromatin is in the highly compacted form and is visible in the light microscope as darkly staining heterochromatin (Figure 2.3 on page 23). Heterochromatin is the portion of the genome where there is no RNA synthesis taking place. Euchromatin, which is chromatin that is being transcribed into RNA, is wholly or partly unpacked from the histones to allow it to be read and has a less dense appearance in the microscope. Chromatin is in its most compacted form when the cell is preparing for mitosis, as shown at the top left of Figure 3.5. The chromatin folds and condenses further to form the 1400 nm‐wide chromosomes we see under the light microscope. Because the cell is to divide, the DNA has been replicated, so that each chromosome is now formed by two chromatids, each one a DNA double helix. This means each daughter cell will receive a full set of 46 chromosomes. Figure 3.6 is a photograph of human chromosomes as they appear at cell division.
Prokaryotic Chromosomes
The chromosome of the bacterium E. coli is a single circular DNA molecule of about 4.6 × 106 base pairs. It has a circumference of 1 mm, yet must fit into the 1 μm cell so, like eukaryotic chromosomes, it is coiled, supercoiled, and packaged with basic proteins that are similar to eukaryotic histones. However, an ordered nucleosome structure similar to the “beads on a string” seen in eukaryotic cells is not observed in prokaryotes. Prokaryotes do not have nuclear envelopes so the condensed chromosome, together with its associated proteins, lies free in the cytoplasm, forming a mass that is called the nucleoid to emphasize its functional equivalence to the eukaryotic nucleus.
BrainBox 3.1 Marie Maynard Daly
Marie Maynard Daly working in her lab, c. 1960.
Source: Archives of the Albert Einstein College of Medicine. Photographer Ted Burrows.
Nucleosomes are the first level of DNA packaging, helping to compact the nuclear genome so that it can fit inside the cell. Nucleosomes form when negatively charged DNA binds to positively charged histone proteins. Histones are rich in the positively charged amino acids arginine and lysine. Marie Maynard Daly was a biochemist who studied histones and was able to demonstrate that there were lysine‐rich histones, in addition to the classical arginine‐rich histones that had previously been described in the literature. In 1947, Marie Maynard Daly became the first African American woman to receive a PhD in chemistry in the United States.
Plasmids
Plasmids are small circular minichromosomes found in bacteria and some eukaryotes. They are several thousand base pairs long and are probably tightly coiled and supercoiled inside the cell. Plasmids often code for proteins that confer a selective advantage to a bacterium, such as resistance to a particular antibiotic. In Chapter 8 we describe how plasmids are used by scientists to artificially introduce foreign DNA molecules into bacterial cells.
IN DEPTH 3.2 DNA – A GORDIAN KNOT
At the start of his career Alexander the Great was shown the Gordian Knot, a tangled ball of knotted rope, and told that whoever untied the knot would conquer Asia. Alexander cut through the knot with his sword. A similar problem occurs in the nucleus, where the 46 chromosomes form 2 m of tangled, knotted DNA. How does the DNA ever untangle at mitosis? The cell adopts Alexander's solution – it cuts the rope. At any place where the DNA helix is under strain, for instance, where two chromosomes press against each other, an enzyme called topoisomerase II cuts one chromosome double helix so that the other can pass through the gap. Then, surpassing Alexander, the enzyme rejoins the cut ends. Topoisomerases are active all the time in the nucleus, relieving any strain that develops in the tangled mass of DNA.
Concerns that a terrorist organization might release large amounts of anthrax spores have caused several governments to stockpile large amounts of the antibiotic Cipro. This works by inhibiting the prokaryotic form of topoisomerase II (sometimes called gyrase) hence preventing cell replication.
Source: Image by Mariano Rocchi, Resources for Molecular Cytogenetics, Department of Biology, University of Bari. Reproduced by permission.
Viruses
Viruses (page 4) rely on the host cell to make more virus. Once viruses have entered cells, the cells' machinery is used to copy the viral genome. Depending on the virus type, the genome may be single‐ or double‐stranded DNA, or even RNA. A viral genome is packaged within a protective protein coat. Viruses that infect bacteria are called bacteriophages. One of these, lambda, has a fixed‐size DNA molecule of 4.8 × 104