Cell Division

This is a brief outline of cell division in eukaryotes. For a more detailed description, click the links provided in each section.

Cell division is the process by which cells divide into two or more progeny cells, usually referred to as "daughter" cells. Cell division happens for a number of reasons. Simple unicellular organisms reproduce by cell division. Cell division serves many functions in multicellular organisms, such as growth, replacement of tissues that shed (such as the skin or intestinal lining), or reproduction.

Prokaryotes such as bacteria undergo cell division by a process known as binary fission. This is not covered here. The corresponding process in eukaryotes is mitosis, which is described below. Additionally, multicellular organisms can also use a different process - meiosis - to produce specialized reproductive cells called "gametes". Meiosis is also described below.

Mitosis

Mitosis is the eukaryotic equivalent for binary fission - the process by which a cell splits into two daughter cells. Unicellular eukaryotes reproduce through mitosis. Some multicellular organisms, such as plants which are propagated through cuttings, can also reproduce through mitosis. Mitosis is also used to replace or regenerate lost tissues, for example the skin, or even whole organs in animals which can regenerate body parts. It is involved in wound healing, in the production of immune cells, and in the growth of a zygote to embryo, fetus, newborn, to adult.

Mitosis results in the production of daughter cells which are identical to the mother cell in terms of their genetic makeup. The DNA of the daughter cells is identical to the DNA of the mother cell (apart from any errors that may occur in the duplication process). This is different from meiosis, where the daughter cells are not identical to the mother cells from which they are produced.

The Cell Cycle

Mitosis can be thought of as a cycle, since it can occur many times in the same cell line. A diagram of the cell cycle is shown on the left. The mitotic or cell division phase is quite small, representing about 10-20% of the total cycle time, even in rapidly dividing cells. The cell spends the rest of the time either preparing for mitosis (the G1, S and G2 periods of interphase), or in a quiescent state where it is not dividing and not preparing to divide (G0 state).

The dividing cell goes through a rest and growth period, during which it acquires and processes raw materials to increase in size, and produce multiple copies of cellular organelles such as mitochondria and ribosomes, which will be later divided between the two daughter cells. During this rest phase, the cell also duplicates its DNA. Finally, it enters the mitotic phase, where the duplicated DNA is separated into corresponding groups, to form two separate nuclei. Then the rest of the cell splits into two, with each half getting one nucleus, and two daughter cells are produced. Each of these two daughter cells then enters the rest and growth phase, and in turn can enter a mitotic phase of its own, each producing the next generation of daughter cells. This is why it is considered cyclic - rest and growth - mitosis - rest and growth - mitosis - etc. In this way, a cell can continue subdividing many times, until its cell line reaches senescence, after which it stops dividing. In humans, normal cells can undergo mitosis about 52 times (Hayflick Limit) until it becomes senescent and stops dividing. Senescence is thought to be related to shortening of the telomeres, which are repetitive sequences at the ends of each chromosome. Each time a cell divides, the telomeres become shorter. Presumably, they reach some critical lower limit, after which the cell cannot divide any more. Of course, this applies only to normal cells. Cancerous cells can keep dividing forever, because the enzyme telomerase is activated in such cells, and this enzyme continues to lengthen the telomeres after each division. Some normal cells, such as various cells in embryonic tissue, can also divide many more times than normal adult cells.

The phases of mitosis are described below. It is important to remember that not all eukaryotic cells divide in exactly the same way. The process described below applies to mammals and many other "higher" organisms. However, there are many eukaryotes that undergo mitosis differently. For example, the dissolution of the nuclear membrane shown below does not happen in many molds and lichens. The separation of the chromosomes in anaphase happens within the nuclear membrane (which never disappears in such organisms), and two nuclei are formed inside the same cell. Each of these nuclei can further subdivide, and often there are cells with multiple nuclei. Cytokinesis can then happen later, and each of the nuclei becomes a new cell. In mammals, cytokinesis usually follows the last phase (telophase), but can also sometimes be delayed.

Interphase

This is the long phase in between cell divisions. This is much longer than all the mitotic phases combined (about 90%, compared to 10% of the time the cell spends in mitosis, in mammalian cells). This is the period during which the cell grows and produces organelles and eventually duplicates its DNA.

The figure on the right shows a diagram of a cell during interphase. The bars below show the mitotic "cell cycle". The left bar shows the cell phases - G1, S and G2, which are collectively known as interphase, and M which is the mitotic phase.

The bar on the right shows the subdivisions of the M or mitotic phase, which are P for prophase, M for metaphase, A for anaphase, and T for telophase. These phases are characterized by what is happening to the DNA of the cell. However, during cell division, it is not only the DNA of the cell that divides; it is the whole cell. The division of the cytoplasm, with its various cell organelles, is known as cytokinesis. In mammals, this typically happens after the last phase of mitosis, and results in the production of two daughter cells.

The cell spends the bulk of its time in interphase, the period between two cycles of cell division. Interphase is divided into 3 periods - G1, S and G2. The S period is shown in the figure to the right. This is the period during which the DNA is duplicated. At this time, the DNA (which is normally dispersed through the nucleus and mostly invisible) condenses into discrete, dark staining bodies, called "chromatin".

G1 and G2 are the growth phases, also sometimes referred to as the "gap" phases. This is the period during which cellular organelles such as ribosomes, mitochondria, and other machinery of the cell are produced in large numbers. This material is eventually split between the two daughter cells.

Some cells which are not actively dividing enter a phase termed G0. During this phase, the cell is not preparing to divide. Cellular activities are mostly concerned with sustaining the cell and performing its normal functions, and there is no extra protein synthesis or organelle synthesis as there is when the cell is preparing to divide. There is a point in time during G1, known as the restriction point, which is sort of a checkpoint to cell division. Provided that the cell receives a suitable mitogenic or growth signal by the restriction point, it will continue on towards the S phase and the duplication of the DNA, followed by mitosis. However, if the appropriate signals are not received by the restriction point, the cell reverts to G0.

During interphase, the nuclear membrane is present. The nucleolus (a nuclear structure which is responsible for assembling ribosomes) is clearly visible. DNA is visible in the form of chromatin clumps scattered throughout the nucleus.

Prophase

During prophase, the chromosomes appear for the first time during cell division. Prior to prophase, the DNA is loosely coiled in chromatin bundles, but during prophase it forms itself up into highly ordered elongated structures, called chromosomes.

Chromosomes appear bifurcate, that is, they look like they are made of two identical strands, joined at the middle. This is because the DNA is already duplicated (it was duplicated during the S period of interphase). Each chromosome is made of two chromatids. Some people confuse the terms "chromosome" and "chromatid", so I wrote a brief explanation describing the difference here.

Each chromatid has a structure near its center, called the kinetochore. This is a complex protein attached to the chromosome, which serves as an attachment point for microtubules, which are used to guide the chromatids towards each half of the cell during later phases. As the name "kinetochore" indicates, this is a motor protein, that uses energy in the form of ATP to "climb" its way along the microtubule to one pole of the cell. The kinetochores of sister chromatids are also connected to each other through the centromeres, which are regions of the DNA on each chromatid that are connected to each other. The two sister chromatids of each chromosome are connected to each other through the centromeres.

During prophase, the centrosomes separate and move towards opposite poles of the cell. The centrosome is a microtubule organizing center, which helps in organizing the microtubules or spindle fibers, which guide the movement of chromosomes in later phases of mitosis. Normally, each cell has one centrosome (which consists of two centrioles), which is found associated with the nuclear membrane during most of interphase. However, during the S period of interphase (when the cellular DNA is duplicated), the centrosome is also duplicated, so prior to prophase the cell contains two centrosomes. Each of the centrosomes moves towards opposite poles of the cell, and each daughter cell will inherit one centrosome. Centrosomes play an important part in cell division, but are not absolutely necessary, since cells can divide without centrosomes. Some types of cells (such as higher plants) do not even contain centrosomes, but contain some other form of microtubule organizing centers.

Towards the end of prophase, the nuclear membrane dissolves. This happens in humans and in most other mammalian cells, but as mentioned earlier, not in all eukaryotic cells. There are some plants, fungi and lichens in which the nuclear membranes remain intact through all of mitosis. In such cases, the microtubules from the centrosomes (or other microtubule organizing centers) penetrate the nuclear membrane and attach the chromatids inside the nucleus.

Metaphase

In metaphase, the microtubules originating from the centrosomes (arranged in bundles called spindle fibers) attach to the kinetochores of the chromatids.

The kinetochores can be imagined as somewhat ring-shaped structures, and the end of each spindle fiber is a "hook" that attaches to the ring. Spindle fibers growing from the centrosomes are of two types. One type can be considered the "kinetochore type" fibers, which specifically look for a kinetochore on a chromatid to attach to. In fact, it is thought that an unattached kinetochore continues to broadcast a signal which tells the cell that kinetochore attachment is not yet complete, and therefore the cell is prevented from moving on to the next stage of the cell cycle. Only when all kinetochores are attached to a spindle fiber does this signal cease, and the cell reaches the mitotic spindle checkpoint, which tells it that it's okay to proceed with the next stage.

The other kind of spindle fibers are known as the "non-kinetochore type", and these do not attach to the kinetochores of chromatids. Instead, they attach to similar non-kinetochore type spindle fibers from the opposite centrosome. This network of fibers stretching from one centrosome to the other is called the mitotic spindle. The function of these fibers is to push the two centrosomes apart, increasing the distance between them. This happens in the next phase (anaphase); however the connections necessary for forming this mitotic spindle happen during metaphase.

As a result of kinetochore-type fibers attaching to the kinetochore of each chromatid from opposite sides, each chromatid pair is under two opposite forces which balance each other. Each chromatid of a chromosome is trying to climb up the spindle fiber on its own side. However, since the chromatids are joined in the middle at the centromeres, they can't actually move at this stage. But the presence of these equal and opposite forces lines the chromosome up at the central or equatorial plane of the cell. This happens to every chromosome of the cell.

Therefore, one of the characteristic features of metaphase is that all the chromosomes appear to line up in the middle of the cell, along what's known as the equatorial plane of the cell, as shown in the diagram. This is very common in mammalian cells. However, there are some cells which don't show such a neat lining up of chromosomes, and in those cases the chromosomes tend to oscillate between the two poles, sometimes nearer one centrosome and sometimes nearer the other.

Anaphase

After all the kinetochore type spindle fibers are attached to the chromatids, and the chromosomes are lined up along the equatorial plane, anaphase begins.

The two chromatids of each chromosome are held together by a protein called cohesin. At the start of anaphase, a protein known as separase cleaves the cohesin, separating the two chromatids of each chromosome from each other. Separase is normally present in the cell, but is under inhibition by a protein called securin. Removal of this inhibition (by a protein called M-phase cyclin) is what initiates anaphase.

Separation of the chromatids allows them to start moving up the spindle fibers towards the centrosomes on their respective sides. As mentioned previously, the kinetochores on the chromatids are motor proteins, that attach themselves to the spindle fiber and "drag" themselves along the fiber, pulling the chromatid with them. This process uses energy in the form of ATP.

As the chromatids move along the spindle fibers, the distal ends of the spindle fibers disintegrate, so the fibers appear to shorten as the chromatids move along their lengths.

Recall that in addition to the kinetochore type spindle fibers (along which the chromatids move), there are also non-kinetochore type spindle fibers, which stretch pole to pole across the cell, from one centrosome to the other. These fibers start lengthening towards the end of anaphase, which increases the separation between the two centrosomes (and therefore also increases the separation between the two sets of chromatids, since the chromatids are attached to each centrosome).

At the end of anaphase, the two sets of chromatids (each of which contains 1c/2n DNA, or exactly the same amount of DNA as a normal adult cell) are at the two polar ends of the cell.

Telophase

This is the end phase of mitosis, and it basically reverses the elements of prophase.

The non-kinetochore type spindle fibers continue to elongate, pushing the centrosomes even farther apart and elongating the cell along the polar axis.

Meanwhile, each set of chromatids develops a nuclear membrane around it. This nuclear membrane is made of fragments of the original nuclear membrane which dissolved towards the end of prophase. The completion of the two nuclear membranes results in two separate nuclei, each containing a full complement of the organism's DNA. Note that is only happens in some kinds of cells (most mammalian cells, including human cells). In other organisms, the nuclear membrane never dissolves, and is therefore does not need to be regenerated. In such cases, the maximal separation of the two centrosomes and the consequent elongation of the cell marks the end of telophase.

The chromatids inside each nucleus then appear to "dissolve" - the tightly packed and organized structure is lost as the DNA uncoils, and it reverts to the normal DNA appearance during the cell's resting phase, a loosely organized chromatin network.

The nucleolus reappears inside each nucleus. This is a dark staining body that contains the machinery for assembling ribosomes from ribosomal RNA.

At this point, mitosis is complete, but cell division is not yet complete. In order for that to happen, the cell must divide physically into two daughter cells, which happens during the next phase of cytokinesis. Telophase accounts for about 2% of the cell cycle in dividing cells.

Cytokinesis

This is the last phase of cell division, which occurs after mitosis is complete.

The diagram to the right shows cytokinesis in a typical animal cell. Cytokinesis is very different in plants, which have cell walls.

In animals cells, soon after the end of telophase, cytokinesis begins. The cell, which was already elongated along the polar axis due to the separation of the centrosomes, begins to pinch off in the middle at the equatorial plane. The equatorial plane is the plane along which the chromosomes aligned themselves during metaphase.

The "pinching off" is due to contractile non-muscle type myosin II and actin filaments, which are deposited on the cell membrane in a ring around the equatorial plane. Contraction of this ring produces a cleavage furrow, which continues to deepen as the ring contracts and the cytoplasm in the region is hydrolysed.

As the cell membrane furrow continues to deepen, the mitotic spindle which was previously pushing the two centrosomes apart during telophase is forced into a narrower and narrower communicating gap between the two halves of the cell. The microtubules start to decay across the cell, except in the region of the constriction itself, where they compact to form the midbody structure, a flattened dense patch between the two separating halves of the cell. Finally, the process of abscission cleaves the midbody structure into two halves, and the two daughter cells separate, and cytokinesis is complete.

Cytokinesis in plant cells is very different. Since plant cells have cell walls, there is no constriction of the membrane and no cleavage furrow. Instead, a new cell wall (known as the cell plate) is deposited at the equatorial plane, and a complex procedure beginning with the creation of the phragmoplast begins, which through a series of steps leads to the formation of the two daughter cells. This process is not covered here.

Meiosis

Meiosis is the process by which the number of chromosomes in a cell is reduced to half. This is a part of sexual reproduction in most organisms. Since sexual reproduction usually involves the contribution of two parents to create an offspring, simply adding the DNA of both parents would result in the offspring having twice the DNA of either of its parents. This would continue with each generation doubling the DNA of the previous generation, and is obviously not a workable system.

Therefore, meiosis exists to reduce each parent's contribution to half their normal DNA, and the two halves from mother and father combine to result in the offspring having the same total amount of DNA as either of its parents. This conserves the amount of DNA in a species. Meiosis results in the creation of specialized sex cells called "gametes" in animals (sperm and ova). In plants, the gametes are called eggs and spores. Meiosis is therefore a special form of reductional division, where the amount of DNA in the daughter cells is reduced to half.

Meiosis is slightly different among males and females. In both cases, it results in the formation of gametes - the sperm (or spores in plants) in males, and the ova or eggs in females. The process of meiosis in males is straightforward, and is what is described below. A single spermatogonium (the precursor cell for sperm) produces 4 spermatozoa. However, in females, the special demands of the egg have modified this process. The egg is much larger than the sperm, and contains a bulk of nutrients as well as a profusion of cellular machinery. So while meiosis is similar in females in that a single precursor cell also produces 4 cells at the end, only one of these is the ovum. The other 3 cells are called polar bodies. While genetically identical to the ovum, the division of cytoplasm and cellular organelles is such that the ovum gets the bulk of the material and the polar bodies get very little. There is no difference in the events occurring to the DNA, it undergoes the same process as the DNA in a sperm cell. The only difference is in the asymmetrical distribution of the cytoplasm, with the egg cell being apportioned most of it, and the polar bodies getting very little.

Another difference between mitosis and meiosis is in the timing of the cell divisions and their stages. Mitosis is fairly simple, as described above. Dividing cells undergo mitosis, which consists of a much longer cell rest and growth phase, and a shorter division phase, and this cycle is continued so long as cell division is required. On the other hand, meiosis occurs at very specific times. It varies by animal, so we will consider humans only. In humans, meiosis in males starts at puberty, when sperm are first produced. It continues from then on until death, although the rate of sperm production falls drastically in middle and old age. In females, on the other hand, meiosis starts in the ovaries while still in the fetal stage, in the 3rd trimester of pregnancy - that is, even before birth. However, meiosis only proceeds to the diplotene stage of Prophase I, and then stops. This is why it's commonly said that women are born with a certain fixed number of egg cells. They're not actually egg cells, they are the precursors of egg cells - the primary oocytes, halted at the diplotene stage of Prophase I. This is how the remain until puberty. But even after puberty, further development of the primary oocytes does not continue synchronously. The vast number of these primary oocytes continue to remain in stasis throughout reproductive age, until about the age of 50 when the woman reaches menopause, and then they are destroyed. However, a few primary oocytes are selected to continue further development each month, with the menstrual cycle. These selected cells continue past Prophase I and finish the first part of meiosis, usually referred to as Meiosis I. Then they proceed to Meiosis II, but again development is halted at Metaphase II, at which stage they are called secondary oocytes. Secondary oocytes will not develop any further, and in fact will be discarded with menstrual flow, unless they are fertilized. In humans, at least, it is technically incorrect to say that the sperm fertilizes the egg. The sperm actually fertilizes the secondary oocyte, and the final stages of Meiosis II only happen after fertilization. At the end of the completion of Meiosis II, the secondary oocyte becomes an ovum, with the expulsion of a polar body. Then the nuclei of the sperm and ovum fuse, and the zygote is formed.

Crossing Over

One very important feature of meiosis is homologous recombination, or chromosomal cross over. This is extremely important in producing variability in the offspring, which is an essential feature of evolution. Crossing over occurs during Prophase I of meiosis, which is described in more detail below. However, the actual mechanism of crossing over is described here separately, rather than clutter up the Prophase I section. Once we get started on the outline of the phases of meiosis, we will cover them quickly and somewhat broadly, and not go into too many details. This particular detail is therefore covered in its own section, since it's a very fundamental characteristic of meiosis.

Like cells preparing to undergo mitosis, cells which are destined for meiosis also begin by spending time in a rest and growth phase, in which DNA is duplicated. Also like mitosis, this happens before division even begins. A sperm or ovum precursor cell is a somatic cell, and therefore is 2c/2n, containing 46 chromosomes in 23 pairs. Due to the duplication of DNA before cell division begins, the amount of DNA increases to 4c/2n. So at the beginning of meiosis, the cell actually has 92 chromosomes, though of course chromosomes are not visible at this early stage. A short description of chromosomes which explains the meanings of "2c/2n" can be found here. If you are not sure what these terms mean, it would help to check out that link before proceeding further.

Since each chromosome is a single molecule of DNA (although coiled in a very complex form), it's helpful to consider the whole process with molecules in mind. A normal somatic cell, including the precursor cells for meiosis, have 46 chromosomes, and therefore 46 DNA molecules. These 46 molecules were inherited from the person's parents - 23 from the father, and 23 from the mother. This is why we typically say "23 pairs" rather than "46 chromosomes". Let's consider any chromosome at random, say chromosome number 7. The same process described below applies for all chromosomes, so we can just describe it for chromosome 7, and you can imagine the same thing happening to every chromosome.

Now when we say "chromosome 7", we don't usually mean "chromosome number 7 out of 46". We mean "chromosome pair 7 out of 23". So "chromosome 7" in typical usage actually refers to a pair - to two chromosomes, two molecules of DNA, one of which was inherited from the father and the other from the mother. Each pair of chromosomes is homologous, meaning they contain the same genes in the same locations. Suppose there is a gene for trait X about 2/3rd of the way down from one end of the chromosome. Then there will be a gene for the same trait X on the homologous chromosome, also located at about 2/3rd of the way down from the corresponding end of the homologous chromosome. Every gene on one chromosome of the pair has a corresponding gene on the other chromosome of the pair, in the same location. The difference between these genes is that they may be different alleles of the same gene.

The diagram on the left shows the process of crossing over. The basal state of the precursor cell is shown in the left side of the figure (labeled "A"). A single chromosome is shown, chromosome 7. As we explained above, chromosome 7 actually refers to a homologous pair, which are labeled 7P and 7M respectively, to show that one was inherited paternally (P) and the other maternally (M). So what you see in figure is chromosome pair 7, which consists of two chromosomes, 7P and 7M, each of which is a single molecule of DNA. The letters at the bottom of the figure show that there is only a single copy of each (C1 = copy number 1) in the basal state.

When the cell is preparing for meiosis, the DNA is duplicated. This is shown in the middle part of the figure (labeled B). As you can see, both 7P and 7M are duplicated. The letters at the bottom show that now there are two copies of each - C1 and C2. Although not shown in this simplified diagram, the two copies of each chromosome are connected together in the middle, at a location called the centromere.

Additionally, the two chromosomes in the pair are also connected to each other, and form an assembly which is known as a tetrad - because it has 4 visible chromatids. These chromatids are sometimes referred to by specific names, so it's important to get our terms clear. The two chromatids of each chromosome (C1 and C2 of chromosome 7P, for example), are called "sister chromatids". They are identical to each other, because they were formed by the process of DNA duplication, hence they are "copy 1" and copy 2". So now we have 4 chromatids - two sister chromatids in 7P, and two sister chromatids in 7M. In contrast to sister chromatids, if we consider a single chromatid of 7P and a single chromatid of 7M, these would be called "homologous chromatids". They are not identical to each other. One represents chromosome 7M, and the other represents chromosome 7P, so they are different, though homologous.

The right most part of the figure (labeled C) shows the crossing over process. This happens in the tetrad assembly, and in the process, homologous chromatids exchange bits of DNA with each other. Only two of the homologous chromatids exchange DNA, the other two are unaffected because they do not take part in crossing over.

The 4 chromatids shown in the right part of the figure (labeled C) will end up in the 4 individual cells formed as the result of meiosis. So if this was the process producing spermatozoa in a man, 4 sperm cells would be produced, each containing one of the 4 versions of chromosome 7 shown in part C of the figure. Because of this, all sperm are not identical. From the single precursor cell, 4 different sperm cells were produced, which are described from left to right:

Depending on which of these 4 sperm actually fertilizes the egg, there are 4 possible variations of DNA for chromosome 7 that the man can pass on to his child. Now consider that the same process happens for every chromosome pair, not just chromosome 7. As you can see, a huge range of variation can be present in the sperm, with different admixtures of maternal and paternal characteristics. The same is true for the ova. Based on random chance, a single sperm will fertilize a single ovum, and some specific admixture of maternal and paternal characteristics will be passed on to the progeny.

After crossing over, the tetrad complex separates first into two pairs, and then later each half of a pair further separates into individual chromosomes. These things happen in later stages of meiosis. One last thing to note is that while 22 pairs of chromosomes (the autosomes) are homologous, the 23rd pair isn't necessarily homologous. The 23rd pair is the sex chromosomes. In women, there are two X chromosomes, so crossing over occurs between them in exactly the same way as it occurs in the other 22 pairs of autosomes. However, men have an X and a Y chromosome. The Y chromosome is much smaller than the X, and there are many genes present on X which are simply not present on Y. Still, there are some genes which are present on both, so there is some homologous region between X and Y, and crossing over does indeed take place between these homologous regions on X and Y. But the exchanged regions are much smaller than in autosomes, because the homologous regions are smaller. As mentioned, this is only a concern for males, since in females there is no Y chromosome.

Non-Disjunction

Non-disjunction is an error during cell division. I've written a separate section about it here before I begin with meiosis, since it can happen both during mitosis and meiosis. The results, of course, are different.

The separation of two homologous chromosomes (or two sister chromatids) during anaphase is called disjunction. Sometimes, due to failure of the chromosomes or chromatids to cleave, disjunction might not occur. In such cases one daughter cell will contain a duplicate of a chromosome (or chromatid), while the other daughter cell will be missing one. If this happens to somatic cells, there is a problem with the daughter cells, which may function abnormally or die. However, if this happens during meiosis, there is the chance of the defect being transmitted to the progeny. The progeny will inherit an odd number of chromosomes, and will repeat this odd number throughout every cell of their body.

As a result of non-disjunction, one gamete gets an extra chromosome while another gamete is missing one. Generally, gametes that are missing chromosomes cannot produce a viable offspring (there are exceptions such as if it's missing one X chromosome). However, gametes that have extra chromosomes can produce viable zygotes, which can survive but are diseased. Some of the diseases caused by non-disjunction are:

And finally, a condition in which a chromosome is missing, rather than having an extra chromosome:

These conditions may produce different phenotypes, or in some cases the phenotype might be indistinguishable from normal people.

Finally, let's get to the description of meiosis. Meiosis is divided into two parts - meiosis I and meiosis II. Here are the stages of meiosis.

Stages of Meiosis

stages of meiosis

The Stages of Meiosis

Meiosis I

This is the first part of meiosis, which produces haploid daughter cells from diploid parent cells. This is therefore a reductional division, which changes the cell type from 2n to n. Meiosis I has the following stages.

Interphase I

Interphase precedes Meiosis I, and like in mitosis, is the phase where the cell grows and accumulates energy and cell organelles in preparation for division. The DNA is also duplicated during this phase. Interphase consists of G1 and S phases. Unlike mitosis, there is no G2 phase. It's important to remember that meiosis is not a cycle. The end products of meiosis (sperm and eggs) do not divide further.

During the S phase, DNA is duplicated. The precursor cell (gametogonium) is 2c/2n like all other somatic cells. After DNA duplication in the S phase, it becomes 4c/2n - that is, it has double the amount of DNA of a normal, non-dividing somatic cell, and is diploid. The cell organelles also increase in number, and the cell grows in preparation for meiosis. As in mitosis, chromosomes are not visible during interphase. The DNA is visible in the form of dark staining chromatin granules scattered throughout the nucleus. The nuclear membrane is present and intact.

Prophase I

This is the first stage of meiosis. Recombination, or crossing over, which was described earlier, happens during this stage. Unlike prophase in mitosis, this stage in meiosis is usually subdivided into a number of phases, to describe the added complexities of recombination. These phases are:

Leptotene

This is when the chromosomes first begin to form. They become apparent as thin threads in the nucleoplasm. At this stage, sister chromatids are stuck closely to each other, and appear as single chromosomes. Therefore, only 46 chromosomes are visible, although each chromosome contains twice the normal amount of DNA (since the DNA was duplicated earlier in the S phase of interphase).

Zygotene

This is the next stage, when homologous chromosomes pair up. The visible appearance therefore is of 23 pairs of chromosomes, rather than 46 individual chromosomes randomly scattered around in the nucleoplasm.

Pachytene

This is the stage when recombination actually occurs. The homologous chromosomes which had paired up in the previous stage exchange DNA along homologous regions of non-sister chromatids (remember, "sister chromatid" refers to duplicated DNA, an identical copy that was created during interphase, while "homologous" refers to pairs of chromosomes, each of which was inherited from one parent). In order for recombination to take place, a synpatonemal complex is formed to hold and align pairs of chromosomes. Individual chromatids are not visible in the synaptonemal complex, so the actual process of crossing over cannot be observed.

Diplotene

After recombination is complete, the synaptonemal complex breaks up, and the homologous chromosomes separate slightly. At this stage, homologous chromosomes are again visible. They remain bound together in pairs at the chiasmata, the regions where crossing over took place.

Diakinesis

The chromosomes condense further, and for the first time, the whole tetrad of each pair becomes visible. Each tetrad consists of a chromosome pair (homologous chromosomes), and each chromosome of the pair consists of two sister chromatids (duplicates). The two pairs remain connected and overlapping at the chiasmata.

At this point, prophase I is completed, and like in mitosis, the nucleolus and the nuclear membrane disappear. The two centrosomes (the centrosome was also duplicated during the S phase of interphase) move towards opposite poles of the cell, and the meiotic spindle starts to form. As in the case of mitosis, this spindle consists of microtubules radiating from the centrosomes. Bundles of microtubules are called spindles. Some spindles attach to the kinetochores of chromosomes (kinetochore type spindles). Some don't attach to chromosomes but instead connect to the other centrosome at the opposite pole of the cell (non-kinetochore type, or polar type spindle). Finally, some spindles simply radiate into the nearby cytoplasm to anchor the centrosome (aster type spindles).

Metaphase I

As spindles from the centrosomes attach to the kinetochores of the chromosomes on the side nearer to them, each chromosome comes under dual opposing forces. The kinetochore is a motor body, and tries to "climb up" the spindle towards the centrosome on its side. Since homologous chromosomes are connected to each other, there is a spindle on each side trying to pull them towards its side. Because of the balance of forces, the chromosome pairs line up along the equatorial plane of the cell. This process is exactly like metaphase during mitosis, except that in the metaphase of mitosis, each chromatid had a spindle fiber attached to it, while here each homologous chromosome (which consists of two fused chromatids) has a spindle fiber attached.

Anaphase I

The connections between homologous pairs of chromosomes break apart, and as a result, each chromosome from the pair is free to climb up the spindle fiber on its own side. As a result, one chromosome of each pair moves towards one pole of the cell, and the other chromosome from each pair moves towards the opposite pole of the cell. This results in a haploid number of chromosomes clustering at each end of the cell. Remember, only homologous chromosomes have separated at this point. Each chromosome still has double the normal amount of DNA in the form of two sister chromatids. The cell also elongates due to the lengthening of the polar spindles, which drives the two centrosomes apart. Again, this is exactly like anaphase in mitosis, except that in the anaphase of mitosis, it was the sister chromatids breaking apart and each sister chromatid climbing up the spindle fiber towards the centrosome on its side. Here, the sister chromatids of each chromosome remain fused to each other, and it's one chromosome of each pair of homologous chromosomes that climbs up the spindle fiber on its side.

Telophase I

Chromosomes arrive at the two poles of the cell, 23 chromosomes at each end. Nuclear membranes re-form, enclosing each haploid set of chromosomes. The chromosomes uncoil and and disappear, taking on the appearance of chromatin granules. The spindle fibers dissolve. The nucleoli reappear inside the two nuclei. This is again exactly like telophase in mitosis. Unlike mitosis, each nucleus does not contain 46 chromosomes - each contains only 23 chromosomes, but each chromosome has double the normal amount of DNA.

Cytokinesis I

The cell membrane constricts along the equatorial plane, and pinches off, dividing the cell into two daughter cells. In plant cells, there is no constriction. Instead, a cell wall is laid down along the equatorial plane, as described in the section on cytokinesis for mitosis. The first stage of meiosis is now complete.

Meiosis II

In order to complete meiosis, the two daughter cells formed as the result of meiosis I must subdivide once more, since their chromosomes contain double the usual amount of DNA. As a result of meiosis I and meiosis II, a total of four cells are produced from the original precursor gametogonium cell.

Interphase II

This is a brief period of rest for the cell. It is also known as interkinesis. Unlike interphase I, there is no duplication of DNA, since the chromosomes already contain double DNA. Not all cells have an interkinesis phase. Some cells skip both telophase I and interkinesis, and proceed directly to prophase II (no intermediate stage of 2 daughter cells exists, they go straight from 1 precursor cell to 4 daughter cells).

Prophase II

This is like prophase in mitosis. Chromatin condenses into chromosomes, the nucleoli disappear, and the nuclear membrane dissolves. There are a couple of significant differences compared to prophase in mitosis. First, the cell only has 23 chromosomes, unlike in mitosis where the cell has 46 chromosomes. This is because the cell was already made haploid by the previous meiosis I division. Second, each cell only has one centrosome. Recall that the original gametogonium contained one centrosome, which was duplicated along with the cell's DNA during the S phase of interphase I. However, during the first division (meiosis I), each daughter cell got one centrosome. Since there is no centrosome or DNA duplication during interphase II, these cells start off with only one centrosome, unlike mitotic cells which start off with two. Therefore, in meiosis II, since there is only one centrosome, the single centrosome splits into two centrioles, and each centriole starts moving towards one pole of the cell.

Metaphase II

This is when the spindles form from the two centrioles at the two poles of the cell. Again, 3 types of fibers form - kinetochore type, polar type and aster type, which perform the same functions as in metaphase I. This time though, the two chromatids of each chromosome are seen distinctly, since they separate out (being connected to each other only at the centromere). As the spindle fibers attach to the kinetochore of each chromatid, the opposing forces cause the chromosomes to line up at the equatorial plane. This is very much like metaphase I, except for a couple things. For one, it's the chromatids that are attached to the spindle fibers, not homologous chromosomes, like in metaphase I. The second is the equatorial plane itself, which is rotated 90 degrees compared to the equatorial plane of meiosis I.

Anaphase II

The centromeres are cleaves, allowing each chromatid to climb up the spindle fiber on its side towards the nearer pole. Once the chromatids are separated, they are called chromosomes.

Telophase II

Nuclear membranes are re-formed around each set of chromosomes at the poles. The chromosomes uncoil and disappear; chromatin is once again apparent. The spindle fibers dissolve.

Cytokinesis II

The cell becomes constricted along the equatorial plane, and pinches off, forming two daughter cells from each of the two cells produced during meiosis I (in plant cells there is no constriction, instead a cell wall is laid down). Nucleoli reappear. This is the end of meiosis, with the production of four daughter cells from one gametogonium.

Note that the gametes are haploid, unlike somatic cells, which are diploid. Also note that each gamete has only one centriole, not a complete centrosome which would have two centrioles. When two gametes fuse during fertilization, the zygote will then have a pair of centrioles (one from each gamete), and therefore a full centrosome.

Also note that as mentioned earlier, meiosis produces 4 spermatozoa from each spermatogonium. However, in females, due to the unequal division of cytoplasm and cellular organelles, each oogonium produces only 1 egg and 3 polar bodies. Polar bodies are genetically identical to the egg, but they contain very little cytoplasm, and do not take part in fertilization.