The Material of Genetics

1.1 THE CELL

In the very beginning is the single cell within a porous membrane. In most developed animals, the single fertilized egg cell eventually becomes very many cells by a remarkably faithful reproduction in a process called mitosis. It has been estimated (see Section 1.1.3) that the number of cells making up an average human body is in the range of 10 trillion to 100 trillion (10–100×10) and with about the same number of bacterial cells. The large number of human cells will be a mixture of various irregular shapes and sizes often related to the manner in which the cells individually support nerve transmission, muscle contraction, epidermal function and so on in the working organism. These different cell types exist in animals as diverse as fruit flies, roundworms, guinea pigs, mice and humans, all of which have played and will play important roles in our understanding of the contribution of genetics to life. In mammals, there are over 200 different types of cells, ranging in size from one of the largest, namely the female egg, which is just visible to the naked eye, to one of the smallest, the sperm cell, which is produced in the millions. The human egg is round and about 150–200 micrometers (µm) in diameter. Fairly immobile, it is formed before birth and remains until menopause in the female. The human sperm is linear-like, with a tail about 50 µm long and 4 µm wide. It is very mobile, using its tail for propulsion. It is formed during puberty and remains often until death in the male. These reproductive cells differ widely within the animal kingdom. In general, mammalian eggs with no yolk are much smaller than those of non-mammals. The eggs of certain birds may have a diameter of several centimeters. The sperm of a fruit fly is remarkable, see Figure 1.1 for an illustration.

1.1.1 The Contents of a Cell

All cells contain a viscous liquid called the cytoplasm in which are embedded a number of mini-organs called organelles (see Figure 1.2). They make various contributions to the workings of the cell and to the well-being of the animal containing them. A plasma membrane encloses the cell.

Some organelles are particularly relevant (although all are important!) to genetics and a brief description of these follows:

• Ribosome: Millions in each cell, both free in the cytoplasm or attached to the rough endoplasmic reticulum. There are various types, but each consists of a complex of ribosomal ribonucleic acid (RNA) and proteins. They aid in the conversion of deoxyribonucleic acid (DNA) into proteins.

• Endoplasmic reticulum: There are two types. The smooth type is the site of lipid formation and poison detoxification. The rough type is embedded with ribosomes and is the site of protein synthesis. Both are near and sometimes merge with the nucleus.

• Golgi body: Often close to the endoplasmic reticulum, it modifies and sorts proteins for transport to various parts of the cell, particularly the cell membrane.

• Lysosome: This contains digesting enzymes that destroy bacteria and cell debris.

• Centrosome: In the cytoplasm region surrounding a pair of centrioles.

• Centriole: Consists of nine bundles of microtubules, which aid cell division.

• Microtubule: Consists of many subunits of tubulin. They maintain cell shape and move fluids over cell surfaces.

• Microfilament: Consists of polymerized actin. A few nanometers in diameter, many of them maintain cell structure and movement.

• Nucleolus: A small, dense round body within the nucleus but not membrane-bound in which ribosomal RNA transcription occurs.

The nucleus and mitochondrion are of particular interest to the geneticist and their salient features are shown in Table 1.1.

1.1.2 The Differentiation of Cells: Stem Cells There is a series of complex changes in going from the single cell and finishing with the different specialized cell types. This is termed cell differentiation.

• The union of the sperm and the egg cell produce a starter cell termed a zygote (see Figure 1.3). In animals, this fertilized egg is almost perfectly round. It divides rapidly by mitosis and, in doubling, continuously forms 2, 4, 8, 16 and so on cells. The zygote becomes the embryo after the first zygotic division and the fetus after the eighth week.

• The fertilized egg and the first few cells are totipotent stem cells (see Figure 1.3). These are capable of forming any of the cells of the body, as well as the placenta and embryo. These cells start to become specialized, and in humans become a clump of 10–20 cells in the inner cell mass (ICM) within the globular blastocyst (around 150 cells) after about 3 to 5 days.

• The ICM yields the pluripotent or embryonic stem cells. These can also form any of the 200 cell types of the body but not the placenta nor the embryo. They can then propagate themselves for long periods. They create most of the cells and tissues that make up a body, such as muscle and nerve cells, skin and hair, etc. (see Figure 1.3).

• Non-embryonic tissue-specific stem cells in adults appear throughout the body in small amounts and are used to replace non-functional or dead cells. Outside of the US, stem cells have been used in regenerative medicine to help repair damaged and diseased cells in people who, for example, have suffered massive strokes. Adult stem cells can usually only generate the type of cell from their tissue of origin. Those from bone marrow can, therefore, only generate red or white blood cells. This fact has been used for years in bone marrow transplants to treat certain bone/blood cancers.

Normal somatic cells, e.g., skin tissue or blood, can now be converted genetically into pluripotent stem cells, termed induced pluripotent stem (iPS) cells. Their use circumvents the ethical problem of human embryo destruction necessary in producing embryonic stem cells. iPS cells are likely to be important in studying a number of diseases, type 1 diabetes and osteoarthritis, for example. Stem cells feature in Chapter 8.

1.1.3 The Lifetimes of Cells

In humans, the average number of times the cell population doubles by division before the cells stop dividing (senescence) and finally commit suicide (apoptosis) is 40–50 times. This means something over 2, which suggests that 10 cells will be formed in that time. There appears to be a rough correlation between the average lifetime of an animal and the doubling number (see Section 3.2.2).

The natural lifetime of the different cell types in an animal varies widely. In humans, skin epidermis cells are replaced every 10–30...