Meiosis is preceded by an interphase consisting of the G1, S, and G2 phases, which are nearly identical to the phases preceding mitosis. The G1 phase, which is also called the first gap phase, is the first phase of the interphase and is focused on cell growth. The S phase is the second phase of interphase, during which the DNA of the chromosomes is replicated. Finally, the G2 phase, also called the second gap phase, is the third and final phase of interphase; in this phase, the cell undergoes the final preparations for meiosis.
During DNA duplication in the S phase, each chromosome is replicated to produce two identical copies, called sister chromatids, that are held together at the centromere by cohesin proteins. Cohesin holds the chromatids together until anaphase II. The centrosomes, which are the structures that organize the microtubules of the meiotic spindle, also replicate. This prepares the cell to enter prophase I, the first meiotic phase.
Early in prophase I, before the chromosomes can be seen clearly microscopically, the homologous chromosomes are attached at their tips to the nuclear envelope by proteins. As the nuclear envelope begins to break down, the proteins associated with homologous chromosomes bring the pair close to each other. (Recall that, in mitosis, homologous chromosomes do not pair together. In mitosis, homologous chromosomes line up end-to-end so that when they divide, each daughter cell receives a sister chromatid from both members of the homologous pair.) The synaptonemal complex, a lattice of proteins between the homologous chromosomes, first forms at specific locations and then spreads to cover the entire length of the chromosomes. The tight pairing of the homologous chromosomes is called synapsis. In synapsis, the genes on the chromatids of the homologous chromosomes are aligned precisely with each other. The synaptonemal complex supports the exchange of chromosomal segments between non-sister homologous chromatids, a process called crossing over. Crossing over can be observed visually after the exchange as chiasmata (singular = chiasma) (Figure 1).
In species such as humans, even though the X and Y sex chromosomes are not homologous (most of their genes differ), they have a small region of homology that allows the X and Y chromosomes to pair up during prophase I. A partial synaptonemal complex develops only between the regions of homology.
Located at intervals along the synaptonemal complex are large protein assemblies called recombination nodules. These assemblies mark the points of later chiasmata and mediate the multistep process of crossover—or genetic recombination—between the non-sister chromatids. Near the recombination nodule on each chromatid, the double-stranded DNA is cleaved, the cut ends are modified, and a new connection is made between the non-sister chromatids. As prophase I progresses, the synaptonemal complex begins to break down and the chromosomes begin to condense. When the synaptonemal complex is gone, the homologous chromosomes remain attached to each other at the centromere and at chiasmata. The chiasmata remain until anaphase I. The number of chiasmata varies according to the species and the length of the chromosome. There must be at least one chiasma per chromosome for proper separation of homologous chromosomes during meiosis I, but there may be as many as 25. Following crossover, the synaptonemal complex breaks down and the cohesin connection between homologous pairs is also removed. At the end of prophase I, the pairs are held together only at the chiasmata (Figure 2) and are called tetrads because the four sister chromatids of each pair of homologous chromosomes are now visible.
The crossover events are the first source of genetic variation in the nuclei produced by meiosis. A single crossover event between homologous non-sister chromatids leads to a reciprocal exchange of equivalent DNA between a maternal chromosome and a paternal chromosome. Now, when that sister chromatid is moved into a gamete cell it will carry some DNA from one parent of the individual and some DNA from the other parent. The sister recombinant chromatid has a combination of maternal and paternal genes that did not exist before the crossover. Multiple crossovers in an arm of the chromosome have the same effect, exchanging segments of DNA to create recombinant chromosomes.
The key event in prometaphase I is the attachment of the spindle fiber microtubules to the kinetochore proteins at the centromeres. Kinetochore proteins are multiprotein complexes that bind the centromeres of a chromosome to the microtubules of the mitotic spindle. Microtubules grow from centrosomes placed at opposite poles of the cell. The microtubules move toward the middle of the cell and attach to one of the two fused homologous chromosomes. The microtubules attach at each chromosomes’ kinetochores. With each member of the homologous pair attached to opposite poles of the cell, in the next phase, the microtubules can pull the homologous pair apart. A spindle fiber that has attached to a kinetochore is called a kinetochore microtubule. At the end of prometaphase I, each tetrad is attached to microtubules from both poles, with one homologous chromosome facing each pole. The homologous chromosomes are still held together at chiasmata. In addition, the nuclear membrane has broken down entirely.
During metaphase I, the homologous chromosomes are arranged in the center of the cell with the kinetochores facing opposite poles. The homologous pairs orient themselves randomly at the equator. For example, if the two homologous members of chromosome 1 are labeled a and b, then the chromosomes could line up a-b, or b-a. This is important in determining the genes carried by a gamete, as each will only receive one of the two homologous chromosomes. Recall that homologous chromosomes are not identical. They contain slight differences in their genetic information, causing each gamete to have a unique genetic makeup.
This randomness is the physical basis for the creation of the second form of genetic variation in offspring. Consider that the homologous chromosomes of a sexually reproducing organism are originally inherited as two separate sets, one from each parent. Using humans as an example, one set of 23 chromosomes is present in the egg donated by the mother. The father provides the other set of 23 chromosomes in the sperm that fertilizes the egg. Every cell of the multicellular offspring has copies of the original two sets of homologous chromosomes. In prophase I of meiosis, the homologous chromosomes form the tetrads. In metaphase I, these pairs line up at the midway point between the two poles of the cell to form the metaphase plate. Because there is an equal chance that a microtubule fiber will encounter a maternally or paternally inherited chromosome, the arrangement of the tetrads at the metaphase plate is random. Any maternally inherited chromosome may face either pole. Any paternally inherited chromosome may also face either pole. The orientation of each tetrad is independent of the orientation of the other 22 tetrads.
This event—the random (or independent) assortment of homologous chromosomes at the metaphase plate—is the second mechanism that introduces variation into the gametes or spores. In each cell that undergoes meiosis, the arrangement of the tetrads is different. The number of variations is dependent on the number of chromosomes making up a set. There are two possibilities for orientation at the metaphase plate; the possible number of alignments therefore equals 2n, where n is the number of chromosomes per set. Humans have 23 chromosome pairs, which results in over eight million (223) possible genetically-distinct gametes. This number does not include the variability that was previously created in the sister chromatids by crossover. Given these two mechanisms, it is highly unlikely that any two haploid cells resulting from meiosis will have the same genetic composition (Figure 3).
To summarize the genetic consequences of meiosis I, the maternal and paternal genes are recombined by crossover events that occur between each homologous pair during prophase I. In addition, the random assortment of tetrads on the metaphase plate produces a unique combination of maternal and paternal chromosomes that will make their way into the gametes.
In anaphase I, the microtubules pull the linked chromosomes apart. The sister chromatids remain tightly bound together a the centromere. The chiasmata are broken in anaphase I as the microtubules attached to the fused kinetochores pull the homologous chromosomes apart (Figure 4).
Telophase I and Cytokinesis
In telophase, the separated chromosomes arrive at opposite poles. The remainder of the typical telophase events may or may not occur, depending on the species. In some organisms, the chromosomes decondense and nuclear envelopes form around the chromatids in telophase I. In other organisms, cytokinesis—the physical separation of the cytoplasmic components into two daughter cells—occurs without reformation of the nuclei. In nearly all species of animals and some fungi, cytokinesis separates the cell contents via a cleavage furrow (constriction of the actin ring that leads to cytoplasmic division). In plants, a cell plate is formed during cell cytokinesis by Golgi vesicles fusing at the metaphase plate. This cell plate will ultimately lead to the formation of cell walls that separate the two daughter cells.
Two haploid cells are the end result of the first meiotic division. The cells are haploid because at each pole, there is just one of each pair of the homologous chromosomes. Therefore, only one full set of the chromosomes is present. This is why the cells are considered haploid—there is only one chromosome set, even though each homolog still consists of two sister chromatids. Recall that sister chromatids are merely duplicates of one of the two homologous chromosomes (except for changes that occurred during crossing over). In meiosis II, these two sister chromatids will separate, creating four haploid daughter cells.