Mitosis

Mitosis is the process whereby a cell divides its chromosome complement evenly between its daughter cells; karyokinesis describes the complete process, including mitosis, through which the nucleus of a cell gives rise to a nucleus in each of its daughter cells. Normally, karyokinesis is accompanied by cytokinesis, the division of the cytoplasm (including organelles and inclusions) between the daughter cells. Thus, karyokinesis and cytokinesis in combination give rise to two daughter cells that in principle are genetically identical to the parent cell, each receiving the complete diploid chromosomal complement (Fig. 4-5). Mitosis is one phase of the somatic cell cycle, the other phase being interphase. Interphase is subdivided into a gap phase 1 (G1), a DNA-synthetic phase (S) and a gap phase 2 (G2). During the S-phase, each chromosome replicates its DNA to produce two chromatids. As already mentioned, the diploid chromosome complement is referred to as 2n. Before the S-phase, each chromosome consists of a single DNA strand, and so each gene is present in two copies (2c), one of maternal and one of paternal origin. After the S-phase, because each chromosome now consists of two chromatids, each gene will be present in four copies (4c) although the chromosome number is maintained at 2n. During the G1-, S- and G2-phases the chromosomes are extremely long, spread through the nucleus in particular domains, and cannot be recognized with the light microscope.

Fig. 4-5: Phases of mitosis: A: G2 of interphase; B: Prophase; C: Pro-metaphase; D: Metaphase; E: Anaphase; F: Telophase; G: Daughter cells in G1 of interphase.

Courtesy Sinowatz and Rüsse (2007).

Mitosis can be subdivided into pro-, meta-, ana- and telo- phases. When the cell moves from G2 of the interphase into the prophase of mitosis, the chromosomes coil, contract, condense and thicken (Fig. 4-5 B). They become visible with the light microscope and each can be seen to consist of two chromatids, joined at a narrow region known as the centromere. Also during the prophase, the centriole pair duplicates in the cytoplasm adjacent to the nucleus and the resultant two pairs become arranged at opposite poles of the nucleus. As the cell moves from pro- towards metaphase (a stage often referred to as pro-metaphase), microtubules starts to form from the two pairs of centrioles and the nuclear envelope begins to dismantle (Fig. 4-5 C). Some of the microtubules from each centriole pair then attach to structures on the chromatids, the kinetochors, that are found in the centromere of each chromosome. This establishes the mitotic spindle with a centriole pair at each pole. Other microtubules pass continuously from one centriole pair to the other without attaching to the chromosomes. As the spindle forms, the chromosomes line up in its equatorial plane, defining the metaphase of the cell division (Fig. 4-5 D). Subsequently, the centromere of each chromosome divides, the two chromatids separate and, pulled by the microtubules, they start to migrate towards the spindle poles during anaphase (Fig. 4-5 E). By this stage, each chromatid has transformed into a new chromosome. Arrangement of the chromosomes into two groups, one at each spindle pole, establishes the telophase of the division (Fig. 4-5 F). Further into telophase, the chromosomes uncoil and lengthen, and a nuclear envelope re-forms in each of the nascent daughter cells (Fig. 4-5 G). This event completes the division of the nucleus and its DNA (karyokinesis) into two daughter nuclei that contain the same DNA sequences and the same number of chromosomes as the initial parental nucleus (2n, 2c). Karyokinesis is followed by cytokinesis to divide the cytoplasm equally between the daughter cells.

Meiosis

Meiosis is a process involving two specialized cell divisions (meiosis I and II) that take place in the germ cells in order to generate haploid maternal and paternal gametes, the oocyte and the spermatozoon. Each of the two meiotic divisions includes the same phases as are in mitosis: pro-, meta-, ana- and telophase except for the lack of prophase in meiosis II. Besides producing gametes with the haploid complement of chromosomes, a second, and equally important, function of meiosis is to allow for genetic recombination; the process that ensures that the genome of the next generation will be a unique combination of parental genomes. The most complex processes occur during meiosis I, which is characterized by a particularly long prophase that can be subdivided into leptotene, zygotene, pachytene and diplotene stages, and diakinesis. It is beyond the scope of this text to address each of these substages beyond saying that they take their names from the morphological appearance of the chromosomes. As soon as the germ cell has initiated meiosis I the maternal one is referred to as a primary oocyte while the paternal equivalent is a primary spermatocyte. In the female, meiosis is initiated during fetal life, then becomes arrested at the diplotene stage of meiosis I until after puberty, and is only resumed shortly before ovulation. This prolonged duration of the diplotene stage is also known as the dictyate stage. In the male, on the other hand, meiosis is not initiated until after puberty but it then becomes a continuous process.

Crossover and genetic recombination

As in mitosis, maternal and paternal germ cells (oogonia and spermatogonia) undergo an S-phase before initiating meiosis. This forms two chromatids in each chromosome (2n, 4c) as in mitosis. This is the status of the germ cell when it enters the leptotene stage of the prophase of meiosis I (Fig. 4-6). In contrast to mitosis, however, the homologous chromosomes align in pairs during the prophase of meiosis I. Each chromosome pair therefore consists of four chromatids (4c) and is therefore referred to as a tetrad.

Fig. 4-6: Phases of meiosis in the male (A) and female (B).

Courtesy Sinowatz and Rüsse (2007).

In the tetrad, each maternal chromatid becomes bound to its paternal counterpart over its full length by the synaptonemal complex. The chromatids match perfectly, point for point, in the female; so they do in the male, except for the XY-combination where the smaller Y-chromosome does not match the X-chromosome. This chromosome pairing allows for interchange of chromatid segments through a crossover process. The chromatids twist, or crossover, at certain points (the chiasmata) to form an X-like structure. Later during the prophase, the synaptonemal complex is gradually broken down, the DNA breaks in the chiasmata, and the free ends of the counterparts join up, thereby exchanging segments of DNA between maternal and paternal chromatids. This chromatin exchange, together with the random segregation of maternal and paternal chromosomes during meiosis II (see later), provide the molecular background for the genetic recombination that is characteristic of sexual reproduction.

During diakinesis, the homologous chromosomes are gradually released from each other. With the transition from diakinesis to metaphase of meiosis I, the nuclear envelope disappears and meiotic spindles are formed. In the male germ cell, the poles of the meiotic spindle are constituted by centriole pairs as during mitosis. However, in at least the large domestic species and in contrast to those of mice, the oocyte lacks centrioles and the spindle poles are made up by unknown material ultrastructurally recognizable as small clusters of vesicles. The microtubules of the spindle attach to each homologous chromosome in a tetrad in meiosis I instead of to the chromatids as they do in mitosis. During the metaphase of meiosis I the chromosomes align in the equatorial plane but, during anaphase, it is the homologous chromosomes, not their chromatids, that are pulled apart to become grouped at the poles of the spindle during telophase. Thus, in contrast to mitosis, meiosis I separates homologous chromosomes rather than chromatids. Upon completion of meiosis I, the germ cell is haploid, containing only one chromosome (1n) from each chromosome pair. It must be underlined, however, that the DNA content of the germ cell at this stage is still 2c because each chromosome consists of two chromatids.