Biology: The Cell Cycle & Cell Division

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The Cell Cycle & Cell Division

In a eukaryotic cell, DNA is located in chromosomes in the nucleus. It contains hereditary information, which is transferred to daughter cells when the parental cell divides. In any particular species, the number of chromosomes in each body cell is constant. Mitosis is the division of the nucleus that produces two daughter nuclei, with chromosomes that are identical in number and type to each other and to the parent nucleus. If the control of mitosis is fault, damage and disease may occur, including the unregulated cell division that is cancer. Meiosis is the division that halves the chromosome number and precedes the formation of gametes.

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Cells & Chromosomes

Chromosome Structure

Chromosomes are made of DAN and a protein called histone. The DNA molecules is a double helix, running the length of the chromosome, with sections along its length called genes. Chromosomes only become visible when chromatin condenses prior to division, after each DNA molecule has replicated and made an exact copy of itself. The two copies of a chromosome are sister chromatids and they lie parallel along their length joined at a specialised region, called the centromere.

Chromatid: One of the two identical copies of a chromosome, joined at the centromere prior to cell division.

Centromere: Specialised region of a chromosome where two chromatids join ad to which the microtubules of the spindle attach at cell division.

The DNA at the centromere has a short sequence of bases that repeats many times. It maintains structure but does not carry genetic information.

Ploidy Level & Chromosome Number

Different species have different numbers of chromosomes in their cells. Normal human body cells have 46 chromosomes, a fruit fly has 8 and a potato has 48.

The number of chromosomes in a complete set is the haploid number, given the symbol n. Many organisms, including humans, receive one complete set of chromosomes from each parent and so the chromosomes occur in matching pairs, called homologous pairs. Humans, therefore, have 23 pairs of homologous chromosomes, in two sets, and are described as diploid, with the symbol 2n. The number of complete sets of chromosomes in an organism is its ploidy level. Organisms with more than two complete sets of chromosomes are described as polyploid.

Diploid organisms have haploid gametes.

Diploid: Having two complete sets of chromosomes.

Haploid: Having one complete set of chromosomes.

Homologous: The chromosomes in a homologous pair are identical in size and shape and they carry the same gene loci, with genes for the same characteristics. One chromosome of each pair comes from each parent. Some pairs of sex chromosomes, such as the X and Y in male mammals, are different sizes and are not homologous pairs.

There is a large range in chromosome number. The smallest possible number of pairs is one (2n = 2), seen in the jumping jack ant. Some mosses have several hundred chromosomes, and the adder's tongue fern has 630 pairs (2n = 1260).

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Mitosis & The Cell Cycle

Mitosis produces two daughter cells that are genetically identical to the parent cell and to each other. Diving cells undergo a regular pattern of events known as the cell cycle. This is a continuous process but, for convenience, it is divided into:

1. Interphase, a period of synthesis and growth.

2. Mitosis, the formation of two genetically identical daughter nuclei. There are four stages called prophase, metaphase, anaphase and telophase.

3. Cytokinesis, the division of the cytoplasm to form two daughter cells.

Mitosis: A type of cell division in which the two daughter cells have the same number of chromosomes and are genetically identical with each other and the parent cell.

Interphase

Interphase is the longest phase of the cell cycle, with much metabolic activity. The newly formed cell grows and its organelles replicate, replacing those lost in the previous division. The DNA replicates so its quantity doubles. Proteins, such as histones and enzymes, are synthesised during interphase, requiring energy from ATP. The chromosomes are not visible in the microscope because the nuclear material, chromatin, is dispersed throughout the nucleus.

The part of interphase in which DNA is replicated is called S phase, where S stands for "synthesis".

Interphase is the longest phase of the cell cycle. It is not a "resting" phase. Cells in interphase are biochemically very active.

Some fly embryo cells have a cell cycle time of 8 minutes, but some cells in the human liver take a year. A mammalian cell may take about 24 hours to complete a cell cycle, of which approximately 90% is interphase.

The Stages of Mitosis

Interphase and cytokinesis are not phases of mitosis.

Prophase

Prophase is the longest of the four stages of mitosis, when the following changes happen:

1. The chromosomes condense. They coil, getting shorter and thicker and become visible as long thin threads. They become distinguishable as pairs of chromatids.

2. Centrioles are present in animal cells; the pairs separate and move to the opposite ends (poles) of the cell, organising a partner as they move.

3. Protein microtubules form, radiating from each centriole, making the spindle. Spindle fibres extend from pole to pole and from pole to the centromere of each chromosome.

4. Towards the end of prophase the nuclear envelope disintegrates and the nucleolus disappears.

Pairs of chromatids can clearly be seen lying free in the cytoplasm.

Metaphase

At metaphase, chromosomes attach to the spindle fibres at their centromeres and align on the equator. If the cell is viewed from the pole, the chromosomes appear spread out, but if the cell is viewed from the side, the chromosomes appear in a line.

Chromatids are genetically identical. Chromosomes are in pairs, which are homologous but are not genetically identical.

DNA replication happens during interphase, before mitosis.

Anaphase

Anaphase is a very rapid stage. The centromere separates and the spindle fibres shorten, pulling the now separated chromatids to the poles, centromere first.

The spindle fibres get shorter, but they do not "contract": only muscle contracts. The microtubules that make up the spindle fibres are polymers of the protein tubulin. They shorten because some of the tubulin is removed, from the centriole end.

Telophase

This is the final stage of mitosis. The chromatids have reached the poles of the cells and are referred to as chromosomes again. You can think about telophase as reversing some of the changes of prophase.

1. Chromosomes uncoil and lengthen.

2. The spindle fibres break down.

3. The nuclear envelope re-forms.

4. The nucleolus reappears.

Cytokinesis

The division of the nucleus by mitosis is followed by cytokinesis, the division of the cytoplasm, to make two cells. In animal cells, cytokinesis occurs by constriction of the parent cell around the equator, from the outside, inwards. In plant cells, droplets of cell wall material, a cell plate, form across the equator of the parent cell from the centre outwards and they extend and join to form the new cell wall.

Differences Between Mitosis in Animal Cells and Plant Cells

Animal Cells

Shape: Cell becomes rounded before mitosis

Centrioles: Present

Cytokinesis: Cleavage furrow; cleavage furrow develops from the outside inwards

Spindle: Degenerates at telophase

Occurrence: In epithelia, bone marrow and other sites

Plant Cells

Shape: No shape change

Centrioles: Absent

Cytokinesis: Cell plate; cell plate develops from the centre outwards

Spindle: Remains throughout new cell wall formation

Occurrence: In meristems

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The Significance of Mitosis

Chromosome Number

Mitosis produces two cells that have the same number of chromosomes as the parent cell and as each other. Each chromosome in the daughter cells is an exact replica of those in the parental cell. So mitosis produces cells that are genetically identical to the parent, giving genetic stability.

Growth

By producing new cells, an organism increases its cell number and can grow, repair tissues and replace dead cells. In plant and animal embryos, body cells are produced by mitosis, so that they are all genetically identical. In adult mammals, some tissues are constantly worn away, such as the skin and the gut lining. Identical cells replace them from below, by mitosis. Mitosis occurs continually in bone marrow, producing red and white blood cells, and also in the nail beds and hair follicles.

Mitosis occurs in plants in small groups of cells, in the root and shoot apex, called meristems.

The meristematic cells in the root apex and the shoot apex remain very small. Mitosis increases the number of cells in a plant, but for a plant to grow, cell expansion must occur. Thus, plants grow by cell expansion, not by cell division.

Mitosis allows for replacement of cells, repair of tissues, asexual reproduction, growth in animals and an increase in cell number in plants.

Asexual Reproduction

Asexual reproduction produces complete offspring that are genetically identical to the parent. It takes place in unicellular organisms such as yeast and bacteria and in some insects, such as greenfly. It also takes place in some flowering plants, where organs such as bulbs, tubers and runners produce large numbers of identical offspring in a relatively short time. However, most of these plants can also reproduce sexually. There is no genetic variation between individuals from asexual reproduction because they are genetically identical.

Damage & Disease

The length of the cell cycle is controlled by genes which ensure that mitosis happens where and when it is needed. This allows for the timely replacement and repair of tissues in adults and for correct development in embryos.

If the genes that control the cell cycle are damaged, cells may fail to divide, may divide too frequently or at the wrong time. Radiation, certain chemicals and some viruses can mutate DNA, and DNA sequencing has identified specific gene mutations that affect the timing of the cell cycle.

Genes control the cell cycle by acting as a brake, preventing the cell cycle from repeating continually. If such genes are mutated, the brake is damaged and the cell may go immediately from one round of mitosis to the next and cells will replicate too fast. If this happens in solid tissue, i.g. in the wall of the colon, a tumour forms. If it is in the bone marrow, so many immature blood cells accumulate, that they spill out into the general circulation as blood cancers, such as leukaemia. These genes are called "tumour suppressor genes" because they prevent rapid replication, which would lead to tumour formation.

Thus, some genes have the potential to cause cancer, if they become mutated or the cell is infected with a virus. Before they are altered, when they do not cause cancer, they are called proto-oncogenes. But once altered and able to cause cancer, they are called oncogenes.

Some chemicals inhibit the cell cycle and have been developed for use against cancer. They are highly toxic and risk damaging normal cells, as well as killing cancer cells.

1. Methotrexate is incorporated into DNA and prevents replication.

2. Doxorubicin targets enzymes essential for the cell cycle to proceed.

3. Vinblastine and vincristine prevent spindle formation.

Oncogene: A gene with the potential to cause cancer.

A well-known gene associated with cancer is the TP53 gene. It codes for a protein, p53, which normally binds to DNA and prevents transcription. It holds the cell cycle at a certain place until more mitosis is needed. DNA sequencing shows that TP53 in different cancer patients has mutations in different bases.

Cancers are the result of uncontrolled mitosis. Cancerous cells divide repeatedly, out of control, with the formation of a tumour, which is an irregular mass of cells. Cancers are sometimes initiated when changes occur in the genes that control cell division.

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Meiosis

Meiosis takes place in the reproductive organs of plants, animals and some protoctistans, prior to sexual reproduction. In the simplest case, it results in the formation of four genetically distinct haploid gametes.

The Number of Chromosomes

In meiosis, the diploid number of chromosomes is halved to haploid. When two haploid gametes fuse at fertilisation, the zygote that is formed has two complete sets of chromosomes, one from each gamete, restoring the diploid condition. If the chromosome number did not halve during gamete formation, the number of chromosomes would double every generation.

Meiosis: A two-stage cell division in sexualyl reproducing organisms that produces four genetically distinct daughter cells each with half the number of chromosomes of the parent cell.

Meiosis Has Two Divisions

Meiosis I is sometimes called a "reduction division" because it halves the chromosome number in each cell.

In meiosis I, homologous chromosomes separate. In meiosis II, chromatids separate.

DNA replication in interphase is followed by two divisions, called meiosis I and meiosis II. Each division goes through the same sequence of steps as mitosis, i.e. prophase, metaphase, anaphase and telophase. The names of the stages are followed by I or II, to distinguish between the two divisions, because the chromosomes behave differently. But between the two divisions, there is no more DNA replication. That only happens once, before meiosis I.

By the end of meiosis I, the homologous pairs of chromosomes have separated, with one chromosome of each pair going into either of the two daughter cells. Each daughter cell has only one of each homologous pair, so they contain half the number of chromosomes of the parent nucleus. In meiosis II, chromatids separate and the two new haploid nuclei divide again. Four haploid nuclei are formed from the parent nucleus, each containing half the number of chromosomes and every gamete is genetically unique.

Chiasma (plural = chiasmata): The site as seen in the light microscope, at which chromosomes exchange DNA in genetic crossing over.

Meiosis I

Prophase I

In prophase I of meiosis paternal and maternal chromosomes come together in homologous pairs. This pairing of chromosomes is called synapsis, and each homologous chromosome pair is a bivalent.

The chromosomes coil up, condensing to become shorter and thicker, visible as two chromatids. In animals and lower plants, where centrioles are present, the centrioles separate and move to the poles of the cells. They organise the polymerisation of microtubules, which radiate out from them, and the spindle forms.

Prophase I differs from prophase of mitosis because the homologous chromosomes associate in their pairs, the bivalents. The chromatids wrap around each other and the partially repel each other but remain joined at points called chiasmata. At a chiasma, a segment of DNA from one chromatid may be exchanged with the equivalent part from a chromatid of the homologous chromosome. This swapping is called crossing over and is a source of genetic variation, because it mixes genes from the two parents in one chromosome. This "genetic recombination" produces new combinations of alleles. A single crossover occurring during meiosis I results in four haploid gametes having a different genetic composition. But crossing over can happen at several places along the length of the chromatid and so there are huge numbers of different genetic combinations made.

By the end of prophase, the nuclear envelope with disintegrated and the nucleolus has disappeared.

Metaphase I

Pairs of homologous chromosomes arrange themselves at the equator of the spindle. In a homologous pair, one chromosome is from the mother and the other is from the father. They lie at the equator randomly, with either one facing either pole. So a combination of paternal and maternal chromosomes faces each pole and the combination of chromosomes that goes into the each daughter cell at meiosis I is random with respect to which parent they came from. This is called independent assortment of chromosomes and produces new genetic combinations, with genes from both parents going into both daughter cells.

When independent assortment happens, with 2 chromosomes, there are 2^2 = 4 possible combinations of maternal and paternal chromosomes in the gametes.

With 3 pairs of chromosomes, there are 2^3 = 8 possible combinations of maternal and paternal chromosomes.

With 23 pairs of chromosomes, there are 2^23 = 8388608 possible combinations of maternal and paternal chromosomes. You do not need to remember this number.

So even if there were no genetic crossing over, there would still be a very large number of different ways genes from the two parents could assort into gametes.

Independent Assortment: Either of a pair of homologous chromosomes moves to either poles at anaphase I of meiosis, independently of the chromosomes of other homologous pairs.

Anaphase I

The chromosomes in each bivalent separate and, as the spindle fibres shorten, one of each pair is pulled to one pole, and the other to the opposite pole. Each pole receives only one of each homologous pair of chromosomes and, because of their random arrangement at metaphase, there is random mixture of maternal and paternal chromosomes.

DNA replication never precedes prophase II, but it always precedes prophase I.

Telophase I

In some species, the nuclear envelope reforms around the haploid group of chromosomes and the chromosomes decondense and are no longer visible. But in many species, the chromosomes stay in the condensed form.

If a nuclear envelope had reformed at telophase I, it would disintegrate again. It happens in meiosis in female mammals because there is a long time between meiosis I and meiosis II. But in male organisms, meiosis II follows meiosis I so rapidly that the nuclear envelope does not re-form: there is no telophase I or interphase.

In pollen formation in plants, all four products of meiosis remain, temporarily, within the original cell wall of the parent cell. These four cells together within one cell wall form a "pollen tetrad".

Cytokinesis

Cytokinesis, the division of the cytoplasm, occurs, making two haploid cells.

Meiosis II

Meiosis II is sometimes described as resembling mitosis, because there is no pairing of homologous chromosomes at metaphase and it is the chromatids, rather than the homologous chromosomes, that separate at anaphase.

Prophase II

The centrioles separate and organise a new spindle at right angles to the old spindle.

Metaphase II

The chromosomes line up on the equator, with each chromosomes attached to a spindle fibre by its centromere. Independent assortment happens because the chromatids of the chromosomes can face either pole.

Independent assortment involves chromosomes in homologous pairs separating at metaphase I and chromatids separating at metaphase II.

Anaphase II

The centromeres divide and the spindle fibres shorten, pulling the chromatids to opposite poles.

Telophase II

At the poles, the chromatids lengthen and can no longer be distinguished in the microscope. The spindle disintegrates and the nuclear envelope and nucleoli re-form.

Cytokinesis

Cytokinesis takes place, producing four haploid daughter cells.

The Significance of Meiosis

1. Meiosis keeps the chromosome number constant from one generation to the next.

2. Meiosis generates genetic variation in the gametes and therefore the zygotes that they produce. These are two ways this happens:

a) Crossing over during prophase I.

b) Independent assortment at:

- Metaphase I, so that the daughter cells contain different combinations of maternal and paternal chromosomes.

- Metaphase II, so daughter cells have different combinations of chromatids.

The Difference between Meiosis I and Meiosis II

Meiosis I

Prophase - Follows DNA replication, includes crossing over

Metaphase - Homologous pairs align either side of the equator, homologous chromosomes undergo independent assortment

Anaphase - Chromosomes separate, two daughter cells are produced, daughter cells are haploid

Meiosis II

Prophase - Does not follow DNA replication, does not include crossing over

Metaphase - Chromosomes align on the equator, chromatids undergo independent assortment

Anaphase - chromatids separate, four daughter cells are produced, daughter cells are haploid

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Comparison of Mitosis & Meiosis

Mitosis

Number of divisions: 1

Number of daughter cells: 2

Chromosome number in daughter cells: Same as parent cell

Ploidy of daughter cells of diploid parent cell: Diploid

Chiasmata: Absent

Genetic crossing over: None

Independent assortment: None

Genetic Composition: Genetically identical with parent cell and each other

Meiosis

Number of divisions: 2

Number of daughter cells: 4

Chromosome number in daughter cells: Half that of parent cells

Ploidy of daughter cells in diploid parent cell: Haploid

Chiasmata: Present

Genetic crossing over: In prophase I

Independent assortment: In metaphase I and metaphase II

Genetic composition: Genetically different