The chromosome and DNA content of cells is defined by the number (n) of different chromosomes (the chromosome set) and the associated DNA content (C). For human cells, n = 23 and C is ~3.5 pg (3.5 × 10−12 g). Different cell types in an organism, however, may differ in DNA content and in ploidy, the number of copies they have of the chromosome set.
Cells differ in DNA content between organisms, between individuals within a species, and within an individual. For any species, the reference DNA content of cells, the C value, is the amount of DNA in cells that have a single chromosome set. C values vary widely for different organisms, but there is no direct relationship between the C value and biological complexity. The human C value is only 19% of that of an onion, for example. We return to consider this in detail in Chapter 13 when we consider our place in the Tree of Life.
Different cells within a single individual show differences in ploidy
The DNA content of cells within a single individual can vary in different ways. We will consider minor differences due to genetic variation in later chapters. Here, we are concerned with differences in chromosome and DNA copy number. In animals, the gametes (sperm and egg cells) may be viewed as reference cells because they carry a single chromosome set; they are said to be haploid (with n chromosomes and a DNA content of C).
Most human and mammalian somatic cells carry two copies of the chromosome set and are diploid (with 2n chromosomes and a DNA content of 2C). Note, however, that in several non-mammalian animal species, most somatic cells are not diploid, but are usually either haploid or polyploid. In the latter case, some are tetraploid (4n) and others have a ploidy >4n (triploidy is less common in animals because it can give rise to problems in producing sperm and egg cells).
Although the majority of human somatic cells are diploid, some cells, for example erythrocytes, platelets, and mature keratinocytes, lose their nucleus and so are nulliploid. Others are naturally polyploid, and are formed in one of two ways. Some cells may become polyploid after undergoing several rounds of DNA replication without cell division (Figure 1A). Examples are hepatocytes (<8C) in the liver, cardiomyocytes (4C–8C) in heart muscle, and megakaryocytes (16C–64C; Figure 1B and C. In other cases, cells may become polyploid through cell fusions. For example, skeletal muscle fiber cells are polyploid as a result of going through multiple rounds of cell fusion. The individual muscle-fiber cells can become very long and contain very many diploid nuclei. Multinucleated cells like this are known as syncytial cells (Figure 1D).
Fig1. Polyploid somatic cells can arise from endomitosis or cell fusion. (A) Principle of endomitosis in which the DNA of a cell replicates but without cell division. (B) The megakaryocyte is a giant polyploid bone marrow cell (often 16C–64C) that is responsible for producing the thrombocytes (platelets) needed for blood clotting. It has a large multilobed nucleus as a result of undergoing multiple rounds of endomitosis. Multiple platelets are formed by budding from cytoplasmic processes of the megakaryocyte and so have no nucleus. (C) Example of a megakaryocyte showing the multilobed nucleus in the center (courtesy of Centers for Disease Control and Prevention [CDC]/ Kathy Keller). (D) Skeletal muscle-fiber cells are polyploid because they are formed by fusion of large numbers of myoblast cells to produce extremely long multinucleated cells. A multinucleated cell is known as a syncytium.
Cells with the normal chromosome number for that type of cell are said to be euploid. However, cells can develop an abnormal number of chromosomes, and are then said to be aneuploid. That can happen either as a result of abnormalities in chromosome segregation, but also occurs by different mechanisms in cancer cells.
Differences in ploidy and DNA content during the cell cycle
The cells of our body are all derived ultimately from a single diploid cell, the zygote, that is formed when a sperm fertilizes an egg. Starting from the zygote, organisms grow by repeated rounds of cell division. Each round of cell division is a cell cycle and comprises a brief M phase, during which cell division occurs, and the much longer intervening interphase, which has three parts (Figure 2). They are S phase (when DNA synthesis occurs), the G1 phase (gap between M phase and S phase), and G2 phase (gap between S phase and M phase).
Fig2. Changes in chromosomes and DNA content during the cell cycle. The cell cycle shown at the right includes a very short M phase, when the chromosomes become extremely highly condensed in preparation for nuclear and cell division. Afterward, cells enter a long period of growth called interphase, during which chromosomes are enormously extended so that genes can be expressed. Interphase is divided into three phases: G1 , S (when the DNA replicates), and G2 . Chromosomes contain one DNA double helix from the end of M phase right through until just before the DNA duplicates in S phase. After the DNA double helix duplicates, the two resulting double helices are held tightly together along their lengths (by specialized protein complexes called cohesins) until the M phase. As the chromosomes condense at M phase they are now seen to consist of two sister chromatids, each containing a DNA duplex, that are bound together only at the centromeres. During M phase the two sister chromatids separate to form two independent chromosomes that are then equally distributed into the daughter cells.
We will describe the cell biology underlying the phases of the cell cycle in Chapter 19. Here, we are mostly concerned with the chromosome and DNA copy number. During each cell cycle, chromosomes undergo profound changes to their structure, number, and distribution within the cell. From the end of the M phase, right through until before DNA duplication in S phase, a chromosome of a diploid cell contains a single DNA double helix, and the total DNA content is 2C (see Figure 2). After DNA duplication, the total DNA content is 4C, but the duplicated double helices are held together along their lengths so that each chromosome has double the DNA content of a chromosome in early S phase. During M phase, the duplicated double helices separate, generating two daughter chromosomes, giving 4n chromosomes. After equal distribution of the chromosomes to the two daughter cells, both cells will have 2n chromosomes and a DNA content of 2C (see Figure 2).
G1 is the normal state of a cell, and the long-term end state of nondividing cells. Cells enter S phase only if they are committed to mitosis; as will be described in more detail in Chapter 3, nondividing cells remain in a modified G1 stage, sometimes called the G0 phase. The cell-cycle diagram can give the impression that all the interesting action hap pens in S and M phases, but this is an illusion. A cell spends most of its life in the G0 or G1 phase, and that is where the genome does most of its work.
A small subset of diploid body cells constitutes the germ line that gives rise to gametes (sperm cells or egg cells). In humans, where n = 23, each gamete contains one sex chromosome plus 22 nonsex chromosomes (autosomes). In eggs, the sex chromosome is always an X; in sperm, it may be either an X or a Y. After a haploid sperm fertilizes a haploid egg, the resulting diploid zygote and almost all of its descendent cells have the chromosome constitution 46,XX (female) or 46,XY (male) (Figure 3).
Fig3. The human life cycle, from a chromosomal viewpoint. Haploid egg and sperm cells originate from diploid precursors in the ovary and testis in women and men, respectively. All eggs have a 23,X chromosome constitution, representing 22 autosomes plus a single X sex chromosome. A sperm can carry either sex chromosome, so that the chromosome constitution is 23,X (50%) and 23,Y (50%). After fertilization and fusion of the egg and sperm nuclei, the diploid zygote will have a chromosome constitution of either 46,XX or 46,XY, depending on which sex chromosome the fertilizing sperm carried. After many cell cycles, this zygote gives rise to all cells of the adult body, almost all of which will have the same chromosome complement as the zygote from which they originated.
Cells outside the germ line are somatic cells. Human somatic cells are usually diploid but, as described above, there are notable exceptions, ranging from nulliploid cells (erythroid cells, terminally differentiated skin cells) to polyploid cells (as in Figure1).
