Cell Cycle and Cell Division

1.0Introduction

• Growth and reproduction are characteristics of cells, indeed of all living organisms. 
• All cells reproduce by dividing into two, with each parental cell giving rise to two daughter cells each time they divide. These newly formed daughter cells can themselves grow and divide, giving rise to a new cell population that is formed by the growth and division of a single parental cell and its progeny. 
• In other words, such cycles of growth and division allow a single cell to form a structure consisting of millions of cells.
• Term mitosis was proposed by Flemming. Mitosis produced genetically identical cells, which are also similar to mother cell.

2.0Cause of Mitosis

1. Kern plasm theory: Hertwig proposed Kern plasm theory. According to this theory mitosis occurs due to disturbance in Karyoplasmic Index (KI) or Nucleocytoplasmic ratio of cell.

Karyoplasmic Index: KI = $\frac{V_n}{V_c-V_n}$

$V_n$ = Volume of nucleus

$V_c$= Volume of cell

$V_c-V_n$ = Volume of cytoplasm

• Karyoplasmic Index of small cell is high as they have less cytoplasm. Nucleus efficiently controls the activity of cytoplasm in small cells.
• In a large cell, nucleus fails to control the activity of cytoplasm. To attain the control of nucleus on metabolism a large cell divides into two cells.

2. Surface-Volume Ratio : Surface-volume ratio is also considered as a cause of cell division. When a cell grows in size its volumes increases more than its surface. So a stage will reach when the surface area of cell becomes insufficient to draw the materials from surrounding. At such critical stage, cell increases its surface volume ratio by division.

3.0Cell Cycle

• Cell division is a very important process in all living organisms.
•  During the division of a cell, DNA replication and cell growth also take place.
•  All these processes, i.e., cell division, DNA replication, and cell growth, hence, have to take place in a coordinated way to ensure correct division and formation of progeny cells containing intact genomes.
• The stages through which a cell passes from one division to the next is called the cell cycle. (The sequence of events by which a cell duplicates its genome, synthesises the other constituents of the cell and eventually divides into two daughter cells is termed cell cycle).
• Although cell growth (in terms of cytoplasmic increase) usually is a continuous process, DNA synthesis occurs only during one specific stage in the cell cycle. 
• The replicated chromosomes (DNA) are then distributed to daughter nuclei by a complex series of events during cell division. These events are themselves under genetic control.

Phases of Cell Cycle

A typical eukaryotic cell divide once in approximately every 24 hours. Yeast can progress through the cell cycle in only about 90 minutes.

Interphase: 

The interphase is divided into three further phases:

(i) G₁ phase (Gap 1)                         (ii) S phase(Synthesis)                                 (iii) G₂ Period of preparation for cell division.

This is phase between two successive M-phase. 

4.0Mitosis phase / M-Phase / Division Phase

• Division phase or M-phase or mitotic phase lasts for only about an hour in the 24-hour duration of cell cycle of a human cell.
• The M-phase represents the phase when the actual cell division or mitosis occurs. In animals, mitotic cell division is restricted or only seen in diploid somatic cell except in some social insects. Against this, the plants can show mitotic division in both haploid and diploid cells.
• This is the most dramatic period of the cell cycle, Since the number of chromosomes in the parent and progeny cells is the same, it is also called as equational division.
• The M-phase starts with nuclear division, corresponding to the separation of daughter chromosomes (Karyokinesis) and usually ends with division of cytoplasm (cytokinesis).

Mitosis has been divided into four stages of nuclear division:

(1) Prophase (2) Metaphase

(3) Anaphase (4) Telophase

(1) Prophase :

• Prophase which is the first stage of karyokinesis of mitosis follows the S and G₂ phases of interphase.
• In the S and G₂ phases the new DNA molecules formed are not distinct but intertwined. 
• Prophase is marked by the initiation of condensation of chromosomal material. The chromosomal material becomes untangled during the process of chromatin condensation.
• The centrioles (Centrosome), which had undergone duplication during S phase of interphase, now begins to move towards opposite poles of the cell.

The completion of prophase can thus be marked by the following characteristic events:

• Chromosomal material condenses to form compact mitotic chromosomes. Chromosomes are seen to be composed of two chromatids attached together at the centromere.
• Centrosome which had undergone duplication during interphase, begins to move towards opposite poles of the cell. Each centrosome radiates out microtubules called asters. The two asters together with spindle fibres forms mitotic apparatus.
• Cell at the end of prophase when viewed under the microscope, do not show Golgi complexes, endoplasmic reticulum, nucleolus and nuclear envelope.

(2) Metaphase : 

The complete disintegration of nuclear envelope marks the start of metaphase

• By this stage, condensation of chromosomes is completed and they can be observed clearly under the microscope. This then, is the stage at which morphology of chromosomes is most easily studied.
• At this stage, metaphase chromosome is made up of two sister chromatids, which are held together by the centromere. Small disc-shaped structures at the surface of the centromeres are called kinetochores. These structures serve as the sites of attachment of spindle fibres (formed by the microtubules) to the chromosomes that are moved into position at the centre of the cell.
• Centromere lies at equator and arms of chromosomes remain directed towards poles.

The key features of metaphase are:

• Spindle fibres attach to kinetochores of chromosomes.
• Chromosomes are moved to spindle equator and get aligned along metaphase plate through spindle fibres to both poles.

(3) Anaphase :

• At the onset of anaphase, each chromosome arranged at the metaphase plate is split simultaneously and the two daughter chromatids, now referred to as daughter chromosomes of the future daughter nuclei, begin their migration towards the two opposite poles. 
• As each chromosome moves away from the equatorial plate, the centromere of each chromosome remains directed towards the pole and hence at the leading edge, with the arms of the chromosome trailing behind
• Number of chromosomes become double in cell.
• The two new daughter chromosomes begin moving toward opposite ends of the cell as their spindle fibres shorten.

Anaphase stage is characterized by the following key events: 

• Centromeres split and chromatids separate.
• Chromatids (now referred as chromosomes) move to opposite poles.

(4) Telophase (Reverse Prophase) :

• At the beginning of the final stage of karyokinesis, i.e., telophase, the chromosomes that have reached their respective poles decondense and lose their individuality.
• The individual chromosomes can no longer be seen and chromatin material tends to collect at each of the two poles.

This is the stage which shows the following key events:

• Chromosomes cluster at opposite spindle poles and their identity is lost as discrete elements.
• Nuclear envelope develops around the chromosome clusters at each pole forming two daughter nuclei.
• Nucleolus, Golgi complex and ER reform.

Cytokinesis

Mitosis accomplishes not only the segregation of duplicated chromosome into daughter nuclei (Karyokinesis) but the cell itself is divided into two daughter cells by the separation of cytoplasm called cytokinesis at the end of which cell division gets completed.

In an animal cell:

• This is achieved by the appearance of a furrow in the plasma membrane. 

• At the periphery of the equator a contractile ring is formed that is made up of actin and myosin protein. 
• Due to interaction between actin and myosin ring contract, thus a furrow forms from outside to inside in cell. The furrow gradually deepens and ultimately joins in the centre dividing the cell cytoplasm into two. In animals’ cytokinesis occurs in centripetal order.

In Plant cells:

• Enclosed by a relatively inextensible cell wall, therefore they undergo cytokinesis by a different mechanism. 
• In plant cells, wall formation starts in the centre of the cell and grows outward to meet the existing lateral walls. The formation of the new cell wall begins with the formation of a simple precursor, called the cell-plate that represents the middle lamella between the walls of two adjacent cells. At the time of cytoplasmic division, organelles like mitochondria and plastids get distributed between the two daughter cells.

• Many Golgi vesicles arrange themselves on equator. Membrane of Golgi vesicles fuse to form a plate like structure called cell plate. Golgi vesicles secret calcium and magnesium pectate. Further cell plate is modified into middle lamella.
• In plants, cytokinesis occurs in centrifugal order (cell plate formation is from centre to periphery).

Special Case in Mitosis:

In some organisms karyokinesis is not followed by cytokinesis as a result of which multinucleate condition arises leading to the formation of syncytium (e.g., liquid endosperm in coconut).

Significance of Mitosis

• Mitosis or the equational division is usually restricted to the diploid cells only. However, in some lower plants and in some social insects haploid cells also divide by mitosis. 
• Mitosis usually results in the production of diploid daughter cells with identical genetic complement. 
• The growth of multicellular organisms is due to mitosis. Cell growth results in disturbing the ratio between the nucleus and the cytoplasm. It therefore becomes essential for the cell to divide to restore the nucleo-cytoplasmic ratio. 
• A very significant contribution of mitosis is cell repair. The cells of the upper layer of the epidermis, cells of the lining of the gut, and blood cells are being constantly replaced. Mitotic divisions in the meristematic tissues – the apical and the lateral cambium, result in a continuous growth of plants throughout their life.
• Development of an organism occurs by mitosis. Every organism starts its life from a single cell i.e. zygote. Repeated mitosis in zygote leads to the formation of the whole body.

5.0Meiosis

• The production of offspring by sexual reproduction includes the fusion of two gametes, each with a complete haploid set of chromosomes. Gametes are formed from specialised diploid cells.

• The specialized kind of cell division that reduces the chromosome number by half results in the production of haploid daughter cells. This kind of division is called meiosis.
• Meiosis ensures the production of haploid phase in the life cycle of sexually reproducing organisms whereas fertilization restores the diploid phase. Meiosis occurs during gametogenesis, leads to the formation of haploid gametes.

Key Features of Meiosis

Meiosis involves two sequential cycles of nuclear and cell division called meiosis I and meiosis II but only a single cycle of DNA replication.

Meiosis - I :

• Heterotypic division or reduction division. It leads to reduction in chromosome numbers. Division of chromosome does not occur in meiosis-I, only segregation of homologous chromosomes takes place.
• Meiosis I is initiated after the parental chromatids have replicated to produce identical sister chromatids at the S phase.
• Meiosis I involve pairing of homologous chromosomes and recombination between non sister chromatids of homologous chromosome.

Meiosis - II :

• This is a homotypic division or equational division. It does not lead to any change in chromosome number.
• Division of chromosome or centromere occurs during meiosis II.
• Four haploid cells are formed at the end of meiosis II. All the four daughter cells produced by meiosis are genetically different from each other and also differ from the mother cell.
• In meiosis, division of nucleus takes place twice but division of chromosome occurs only once in meiosis-II.
• Interphase is same as for mitosis.

Meiotic events can be grouped under the following phases:

Stages of Meiosis - I

Prophase - I :

• Typically, longer and more complex when compared to prophase of mitosis. Prophase I is classified in five substages based on chromosomal behaviour.

Metaphase - I :

• Bivalents arrange on equator (congression) of cell to form metaphase plate. The microtubules (spindle fibres) from the opposite poles of the spindle attach to the pair of homologous chromosomes with one kinetochore of each chromosome.

Anaphase - I :

• Due to shortening of kinetochore/chromosomal fibres homologous chromosomes segregate from each other and move towards the opposite poles. Sister chromatids remain associated at their centromeres (i.e. chromosomes remain in double chromatid stage)
• Anaphase I is characterised by segregation of chromosomes. Division of centromere is absent.

Telophase - I :

• The nuclear membrane and nucleolus reappear. Although in many case the chromosomes do undergo some dispersion, but they do not reach the extremely extended state of the interphase nucleus.
• Cytokinesis follows telophase-I and a diploid (2n) cell divides into two haploid (n) daughter cells. This is called as dyad of cells.

Interkinesis :

• Gap between meiosis I and meiosis II is called Interkinesis. Preparations of meiosis II occur during interkinesis. It is like interphase of mitosis but replication of DNA is absent in interkinesis.
• Interkinesis is generally short lived. Interkinesis is followed by prophase-II, a much simpler prophase than prophase-I.

Stages of Meiosis-II

Prophase – II :

Meiosis II is initiated immediately after cytokinesis, usually before the chromosomes have fully elongated. In contrast to meiosis I, meiosis II resembles a normal mitosis

Metaphase – II:

• At this stage the chromosomes align at the equator and the microtubules from opposite poles of the spindle get attached to the kinetochores of sister chromatids.

Anaphase - II:

• It begins with the simultaneous splitting of the centromere of each chromosome (which was holding the sister chromatids together), allowing them to move toward opposite poles of the cell by microtubules attached to kinetochores.

Telophase - II:

• Meiosis ends with telophase II, in which the two groups of chromosomes once again get enclosed by a nuclear envelope; cytokinesis follows resulting in the formation of tetrad of cells i.e., four haploid daughter cells.

Significance of Meiosis

1. Conservation of specific chromosome number of each species is achieved across generations in sexually reproducing organisms, even though the process (per se, paradoxically) results in reduction of chromosome number by half.
2. It also increases the genetic variability in the population of organisms from one generation to the next. 
3.  Variations are very important for the process of evolution.