NEET Biology Cell Cycle and Cell Division Notes

NEET Biology notes on the cell cycle and cell division covering the phases of the cell cycle, mitosis with its stages (prophase, metaphase, anaphase, telophase and cytokinesis), the significance of mitosis, meiosis with meiosis I and meiosis II, synapsis, crossing over, the significance of meiosis, and the key terms and differences from the chapter.

NEET Biology Cell Cycle and Cell Division Notes

Covers the following topics:
1. Cell cycle and its phases
2. Mitosis (karyokinesis and cytokinesis)
3. Significance of mitosis
4. Meiosis (meiosis I and meiosis II)
5. Significance of meiosis

While going through the chapter pay special attention to the following:

Terms and Definitions:
(1) Synaptonemal complex (2) Chiasmata
(3) Terminalization (4) Brachymeiosis
(5) Bouquet stage (6) Tetrad
(7) G0 stage (8) Asters
(9) Karyochorosis (10) Recombinase enzyme
(11) Disjunction (12) Bivalents
(13) Interkinesis (14) Homotypic division
(15) Heterotypic division

Differences:
(1) Cytokinesis and Karyokinesis
(2) Cytokinesis in plants and animals

CELL DIVISION

New cells arise from pre-existing cells by a process known as cell division. Cell division is an important phenomenon that occurs in all living organisms.

In unicellular organisms, cell division directly produces two individual organisms, so it is a method of reproduction in these organisms. In multicellular organisms, life begins from a single cell, the zygote or fertilised egg, which divides and redivides to form a complete organism.

Each parent cell gives rise to two daughter cells each time it divides. These newly formed daughter cells grow and divide, giving rise to a new cell population formed by the growth and division of a single parental cell and its progeny.

CELL CYCLE

The cell cycle is a genetically controlled series of changes that occur in a newly formed cell, by which it duplicates its genome, synthesises other constituents, undergoes growth and divides to form two daughter cells.

Although cell growth (in terms of cytoplasmic increase) 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.

The cell cycle consists of two basic phases, states or periods: a long, growing interphase (I-phase) and a short, dividing M-phase. Both have sub-stages. The M-phase is the period or phase of actual cell division.

Main reason for cell division: To maintain the nucleocytoplasmic ratio, or karyoplasmic ratio, which is the ratio between the nucleus and the cytoplasm. This ratio gets disturbed due to continuous cell growth. Cell division is also necessary for the continuity of an organism or species.

Connecting concepts: The time interval between two successive divisions is called the generation time. Nerve cells do not divide after birth, and therefore interphase lasts throughout the life of the individual.

PHASES OF CELL CYCLE

Interphase: The resting phase or stage between two mitotic divisions is called inter-mitotic phase or interphase. During interphase, the cell prepares for division by undergoing both cell growth and DNA replication in an orderly manner. Most DNA, RNA and proteins are made during interphase, so it is the period when metabolic activity is greatest. Interphase is the longest phase of the mitotic cycle and lasts more than 95 per cent of the duration of the cell cycle. It has three sub-phases: G1, S and G2, which occur in this order.

In continuously dividing cells, an individual cell passes through the following four phases of the cell cycle. Different eukaryotic cells vary in the length of time taken to complete an entire cell cycle, and they also differ in the relative proportions of time allotted to each of the four stages.

(i) G1 phase (G stands for gap): In this phase, synthesis of the substrate and enzymes necessary for DNA synthesis takes place. Therefore, G1 is marked by the transcription of rRNA, tRNA and mRNA and by the synthesis of different types of proteins. It corresponds to the interval between mitosis and the initiation of DNA replication. During G1 phase, the cell is metabolically active and continuously grows, but does not replicate its DNA.
- Time taken for completion of this phase is about 30 to 40 per cent of the total cell cycle (mitotic cycle).
- The decision of cell division occurs during this phase.
- The point where this decision is made is known as the check point. Once this check point is crossed, the cell will divide even under unfavourable conditions.
- In G1 phase, a cell can undergo three processes: (a) enter the S phase, (b) enter a quiescent stage or G0 phase, or (c) stop the cell cycle and undergo differentiation. The deciding factor is the availability of energy-rich compounds and mitogens.
- G0 phase: Some cells in adult animals do not appear to exhibit division (e.g., heart cells), and many other cells divide only occasionally. These cells, which do not divide further, exit the G1 phase to enter an inactive stage called the quiescent stage (G0). Cells in this stage remain metabolically active but no longer proliferate unless the organism requires it.

(ii) S phase: During the S or synthesis phase, replication or duplication of chromosomal DNA and synthesis of histone proteins takes place. During this time, the amount of DNA per cell doubles.
- Time taken for completion of this phase is 30 to 50 per cent of the total cell cycle.
- If the initial amount of DNA is denoted as 2C, it increases to 4C. However, there is no increase in the chromosome number. If the cell has diploid (2n) chromosomes at G1, the number remains 2n even after the S phase.
- In animal cells, during the S phase, DNA replication begins in the nucleus and the centriole duplicates in the cytoplasm.
- In rapidly growing bacteria, DNA synthesis occurs from the time a cell originates to the time it gives rise to daughter cells by division. In simple eukaryotes such as yeast, DNA synthesis takes place throughout interphase and ceases only during the brief period of nuclear and cell division (M phase).
- Once the cell enters the S phase, it proceeds to division without any interruption.

(iii) G2 phase: It is the post-DNA synthesis phase.
- Time taken for completion of this phase is 10 to 20 per cent of the total cell cycle.
- During G2 phase, proteins are synthesised for mitosis while cell growth continues.

(iv) M phase (mitotic or meiotic phase): It is the actual cell division phase, which follows the G2 phase.
- Time taken for completion of this phase is 5 to 10 per cent of the total cell cycle, and hence it is the shortest of all four phases.
- It is the final phase of the cell cycle. It consists of karyokinesis (division of the nucleus) and cytokinesis (division of the cell protoplasm) to form two daughter cells.

Key facts about the cell cycle:
- The DNA content in G1 is 2C, and in G2 it is 4C.
- Various phases of the cell cycle are controlled by proteins called cyclins and cyclin-dependent kinases (CDKs or cdc kinases), which take part in phosphorylation and dephosphorylation.

Time taken by the phases of the cell cycle in Vicia faba (broad bean or Bakla):

Therefore, the cell cycle here is of 31 hrs (interphase 30 hrs and mitotic phase 1 hr).

In meiotic cells, the G2 phase is either absent or very short, i.e., meiotic division (M phase) occurs just after the completion of DNA synthesis (S phase).

Check Point 1: Give the term for each of the following.
(a) The period between two successive mitotic divisions.
(b) Process of cell division by which the chromosome number is halved.
(c) Point at which two sister chromatids are held together.
(d) Phase in the cell cycle when protein and RNA are synthesised.
(e) Nuclear division.

MITOSIS

Flemming (1882) coined the term mitosis. However, mitosis was first observed in plants by E. Strasburger (1875) and in animals by W. Flemming (1879). Mitosis is also called equational division, as the number of chromosomes in the parent and progeny cells is the same. So mitosis increases the number of cells without any change in genetic constitution.

Mitosis is a continuous process, but for convenience it is divided into several stages or phases: prophase, metaphase, anaphase, telophase and cytokinesis.

Mitosis is also known as somatic division because it takes place during the formation of somatic or body cells. In plants, mitosis is studied in the meristematic regions, e.g., stem tip and root tip. In animals, it is studied in bone marrow, skin, the base of nails, etc.

Mitosis is centric in animal cells, which means it involves the centrosome, and acentric in plants, which means it occurs without the participation of the centrosome.

Agents that affect cell division:
- Mitogens are agents which stimulate cell division, e.g., cytokinins, some steroids, platelet derived growth factor (PDGF) and lymphokines.
- Mitotic poisons are agents which inhibit cell division, e.g., azides, cyanides and colchicine.
- Besides mitogens, cells are stimulated to divide on achieving a particular size, on a critical decrease in surface volume ratio, and on a critical decrease in the nucleocytoplasmic ratio.

The rate of cell division is not the same in various stages of the life cycle. A fertilised egg or zygote divides repeatedly to form a large number of cells, up to 6 x 10¹² cells. Later, divisions slow down and are restricted to certain regions, like meristematic regions in plants, and bone marrow and germinal tissue in animals.

Summary of mitosis (parent cell to two daughter cells):

Prophase

Prophase is the first and the longest phase of mitosis. It includes five events:
1. The beginning of prophase is indicated by the onset of chromosome coiling and condensation. As a result, chromosomes become distinctly visible as thin threads inside the nucleus. At the same time, the cell becomes spheroid, more refractile and viscous.
2. Each prophase chromosome is composed of two coiled identical filaments, the sister chromatids, which are held together by a centromere.
3. The two pairs of centrioles formed by duplication during the S phase of interphase separate and migrate to occupy positions on opposite sides of the nucleus.
4. Initiation of spindle formation begins during prophase, although the spindle is not fully functional until metaphase. Microtubules (proteinaceous components) of the cell cytoplasm help in this process.
5. Cells at the end of prophase do not have a Golgi complex, endoplasmic reticulum, nucleolus or nuclear envelope.

Metaphase

At metaphase, the nuclear envelope completely disintegrates, the chromosomes align, and the spindle apparatus is formed.

The spindle apparatus is a microtubular structure that extends from pole to pole. Cells that have centrioles typically also have asters, which are fibres radiating out in all directions from the poles. Each of the astral and spindle fibres is actually a bundle of microtubules. Small disc-shaped structures at the surface of the centromere are called kinetochores. These are the sites of attachment of spindle fibres. During metaphase, all the chromosomes align at the centre of the cell, and the chromosomes become attached to some of the spindle fibres by their kinetochores.

Spindle fibres are made up of about 97 per cent tubulin protein and 3 per cent RNA. A spindle fibre consists of 4 to 20 microtubules formed of protein tubulin. Spindle microtubules are polar: their plus (+) ends grow fast and face the equator, while their minus (-) ends grow slowly and face the poles. The alignment of chromosomes due to contraction of the chromosomal or kinetochore fibres is called congression.

The two sister chromatids, by virtue of their kinetochores and attached fibres, are pulled towards opposite poles. Because they are held together at the centromere, there is a pull in both directions at once, resulting in oscillatory movements that eventually align all chromosomes in one plane. This plane is called the equatorial plane or metaphasic plane. The fibres of the spindle which connect to the chromosomes are called chromosomal fibres, and those that extend without interruption from one pole to the other are called continuous fibres. The centromeres of all chromosomes lie over the equator, while their arms project in different directions. Chromosome morphology can be observed and studied clearly under the microscope at metaphase.

In dividing animal cells, the spindle bears asters at the two poles. Such a spindle is called an amphiaster, or centric spindle. In plant cells the spindle is acentric or anastral.

In many protists, fungi and algae, the nuclear envelope does not degenerate during mitosis. Instead, the spindle is formed inside the nucleus. This is called intranuclear mitosis or karyochorosis.

Amitosis: In amitosis, the nucleus elongates, constricts in the middle and divides directly into two daughter nuclei. Chromatin does not condense to form chromosomes, and the spindle apparatus is not formed. Nuclear division is followed by cytokinesis. It occurs through cleavage or constriction, e.g., in cartilage cells, the meganucleus of Paramoecium, cells of foetal membranes and endosperm. As amitosis does not distribute chromatin, it leads to structural and functional irregularities.

Anaphase

Anaphase is the phase of shortest duration. Mitotic anaphase begins with the division of the centromere. The two daughter chromatids, now free from each other, move towards their respective poles. Because they are pulled by their kinetochores, the chromatids assume a V-shape, L-shape, J-shape or I-shape in metacentric, submetacentric, acrocentric and telocentric chromosomes respectively.

At the same time, the chromatids move towards their poles, and the poles themselves move further apart. The chromosomes move due to shortening of the chromosomal fibres, and the poles are pushed apart by lengthening (stretching) of the continuous or pole-to-pole fibres. The two sister chromatids are now separate structures and are the chromosomes of the future daughter nuclei. Shape of chromosomes is studied in anaphase.

Telophase

In telophase, two diploid sets of daughter chromosomes gather at opposite poles. They start to uncoil and become a mass of chromatin, and their identity is lost as discrete elements. The nucleolus condenses and reappears. The spindle fibres disperse. The nuclear envelope is assembled around the chromatin mass, and the endoplasmic reticulum reforms, thus forming two daughter nuclei. A cell completes its mitotic division in 10 minutes to several hours. On increasing the surrounding temperature, the time taken for division is lesser.

Connecting concepts: Cancer is a deadly disease caused by uncontrolled cell division. Carcinogens are cancer-causing agents, such as UV radiation and chemicals like benzpyrene, aflatoxin and mustard gas.

Cytokinesis

Karyokinesis (division of the nucleus into two) is followed by cytokinesis, i.e., division of the cytoplasm into two daughter cells. Cytokinesis starts towards the middle of anaphase and is completed simultaneously by the end of telophase.

Plant cells: Wall formation starts in the centre of the cell and grows outward to meet the existing lateral walls (centrifugal). In the equatorial region, the middle part of the spindle persists and gets interdigitated with microtubules to form a complex structure called the phragmoplast. Vesicles of the dictyosome (Golgi complex) and membranous elements of the ER accumulate in the region of the equator and fuse to form the cell plate, dividing the cell into two equal or unequal daughter cells. At the time of cytoplasmic division, organelles like mitochondria, Golgi complex, lysosomes and plastids get distributed between the two daughter cells.

Animal cells: A furrow appears in the cell membrane at the equator and progresses from the periphery to the centre (centripetal). This also occurs in some lower plants.

SIGNIFICANCE OF MITOSIS

Mitosis is necessary for the maintenance and perpetuation of life.
- It helps in maintaining the amount of DNA and RNA in the cell.
- Mitotic divisions of vegetative or somatic cells are responsible for growth and development of the organism.
- Old, decaying and dead cells of the body are replaced by mitosis.
- In certain organisms, mitosis is involved in asexual reproduction.
- The gonads and seed cells depend on mitosis for the increase in their number.
- The cleavage of the egg and division of the blastula during embryogenesis are mitotic divisions.
- Mitotic divisions in the apical and lateral cambium result in continuous growth of plants throughout their life.

MEIOSIS

Farmer and Moore (1905) coined the term meiosis. Meiosis is characterised by two successive divisions of the cytoplasm and nuclei (meiosis I and meiosis II). The haploid cells formed either become or give rise to gametes.

Meiosis ensures the production of the haploid phase in the life cycle of sexually reproducing organisms, whereas fertilisation restores the diploid phase. Thus, meiosis is required to run the reproductive cycle of eukaryotes. Meiosis involves two sequential cycles of nuclear and cell division, called meiosis I and meiosis II, but only a single cycle of DNA replication. It involves the pairing of homologous chromosomes and recombination between them. Four haploid cells are formed at the end of meiosis II.

Brachymeiosis is an unusual meiosis that occurs in the ascus of certain fungi (Pyronema confluens). In this type of division, a reduction division is followed by two usual mitotic divisions to restore the haploid condition in fungi in which double fertilisation has produced a tetraploid primary ascus nucleus.

Meiotic events can be grouped under the following phases:

MEIOSIS I

Meiosis starts after an interphase which is not very different from that of a mitotic interphase. Meiosis I is the actual reduction division and is known as heterotypic division, as it converts a diploid cell into haploid cells. In meiosis I, the two chromatids of a chromosome often become different due to crossing over. The first stage of both meiosis I and meiosis II is prophase. The prophase of the first meiotic division is very significant, because most cytogenetic events, such as synapsis and crossing over, occur during this phase.

Prophase I is the longest stage of meiotic division. It includes the following sub-stages:

Leptotene:
- The chromosomes become gradually visible under the light microscope. Compaction of chromosomes continues throughout leptotene.
- The chromosomes at this stage converge towards one side of the nucleus, where the centrosome lies (the bouquet stage).
- The centriole duplicates, and each daughter centriole migrates towards the opposite poles of the cell. On reaching the poles, each centriole duplicates again, so each pole of the cell possesses two centrioles, or a single diplosome.

Zygotene:
- The leptotene stage is followed by zygotene. In this stage, the pairing of homologous chromosomes takes place. One chromosome of each homologous pair comes from the mother (through the ovum) and one from the father (through the sperm). They are attracted towards each other and their pairing takes place. The pairing of homologous chromosomes is known as synapsis, forming bivalents.
- Synaptonemal complex: Moses (1956) discovered the synaptonemal complex, which is a paired set of homologous chromosomes held together by nucleoproteins. The pairing of homologous chromosomes is very specific, i.e., it brings the alleles of homologous chromosomes exactly opposite to each other. This complex extends along the whole length of the paired chromosomes and is usually anchored at either end to the nuclear envelope. The synaptonemal pairing produces an opportunity for crossing over that occurs during pachytene, and thus facilitates genetic recombination. The paired homologous chromosome is called a bivalent.
- Depending on the area of initiation, synapsis can be procentric (starting from the centromeres), proterminal (pairing beginning from the telomeric regions and proceeding inward) or intermediate (random pairing starting at several points). Pairing proceeds from the starting regions towards other parts in a zipper-like manner.
- In males of Drosophila melanogaster, an unusual type of meiosis occurs in which synaptonemal complex (SC) formation and recombination do not occur. This is called achiasmatic meiosis and is exceptional, as nearly all eukaryotes, along with Drosophila females, require SC formation and recombination for successful completion of meiosis.

Pachytene:
- This stage is characterised by the appearance of recombination nodules, the sites at which crossing over occurs between non-sister chromatids of homologous chromosomes.
- Crossing over is the exchange of genetic material between two homologous chromosomes. It is also an enzyme-mediated process, and the enzyme involved is called recombinase.
- Crossing over leads to recombination between homologous chromosomes, which is completed at the end of pachytene, but the chromatids remain linked at the site of crossing over.
- Bivalents are actually tetrads, but the individual chromatids of the two chromosomes are not clear due to the presence of a nucleoprotein core between them.

Diplotene:
- Further thickening and shortening of chromosomes takes place. The synaptic forces between paired homologues come to an end (the synaptonemal complex appears to dissolve), and the chromatids become clear. The bivalents are now called tetrads.
- The chromatids of the paired homologous chromosomes are physically joined at one or more discrete points having an X-shaped structure called chiasmata. Chiasmata were first seen by Johannsen.
- In oocytes of some vertebrates, diplotene can last for months or years and form lampbrush chromosomes.
- The nucleolus is diminished but still persists. No nuclear membrane can be seen at this stage.

Disjunction is the process of separation of homologous chromosomes.

Diakinesis:
- The final stage of meiotic prophase I is diakinesis. At this stage, the bivalent chromosomes become more condensed and evenly distributed in the nucleus. Ordinarily, the only distinction between diplotene and diakinesis is the more contracted state of the bivalents at diakinesis.
- The nucleolus detaches from the nucleolar organiser and ultimately disappears. The nuclear envelope breaks down.
- During diakinesis, the chiasmata move from the centromere towards the ends of the chromosomes, and the intermediate chiasmata diminish. This movement of chiasmata is known as terminalisation. The chromatids remain connected by the terminal chiasmata.

Metaphase I:
- Spindle fibres attach themselves to chromosomes, and the chromosomes align at the equator.
- The centromere of each chromosome is directed towards the opposite poles. The repulsive forces between the homologous chromosomes increase greatly, and the chromosomes become ready to separate.

Anaphase I:
- Homologous chromosomes, each with its two chromatids (one chromosome from the mother and the other from the father), move towards the opposite poles of the cell and separate from each other. This separation causes two groups of haploid chromosomes at the poles.
- Due to crossing over, the two chromatids of a chromosome do not resemble each other genetically.
- Chromosomes with single or few terminal chiasmata usually separate more readily than longer chromosomes containing many chiasmata.

Telophase I:
- The nuclear membrane and nucleolus reappear, and the chromosomes uncoil.
- After karyokinesis, cytokinesis occurs and two haploid cells are formed. This is called a diad of cells. Both cells pass through a short resting phase, or interphase.
- No DNA replication occurs during this interphase, so the chromosomes at the second prophase are the same double-stranded structures that disappeared at the first telophase.
- In Trillium, both telophase I and prophase II are omitted, and anaphase I directly leads to metaphase II.

Interkinesis is the stage between the two meiotic divisions. It is generally short-lived. Interkinesis is followed by prophase II, which is a much simpler prophase than prophase I.

Check Point 2: Name the stage of cell division.
(a) Crossing over occurs between homologous chromosomes.
(b) Stage of synapsis of homologous chromosomes.
(c) Stage of initiation of cytokinesis.
(d) Movement of daughter chromosomes towards the poles.
(e) Stage of reappearance of nucleoli.

MEIOSIS II

The first meiotic division is followed by a second meiotic division, with or without the intervening interphase. The second meiotic division is actually a mitotic division, known as homotypic division, which divides each haploid meiotic cell into two haploid cells.

Prophase II: The nuclear membrane and nucleolus disappear. The chromosomes, with two chromatids each, become short, thick and compact. Each centriole divides into two, so two pairs of centrioles are formed. Each pair of centrioles migrates to the opposite pole. The microtubules arrange themselves in the form of a spindle at a right angle to the spindle of the first meiosis.

Metaphase II: The chromosomes get arranged on the equator of the spindle. The microtubules of the spindle attach to the kinetochores of the chromosomes. The centromere divides into two, so each chromosome produces two daughter chromosomes.

Anaphase II: The daughter chromosomes move towards the opposite poles due to the stretching of the internal microtubules of the spindle.

Telophase II: The chromatids migrate to the opposite poles and are now known as chromosomes. The endoplasmic reticulum forms the nuclear envelope around the chromosomes, and the nucleolus reappears due to the synthesis of ribosomal RNA (rRNA) and ribosomal proteins. After karyokinesis, cytokinesis follows, resulting in the formation of a tetrad of cells, i.e., four haploid daughter cells.

SIGNIFICANCE OF MEIOSIS

Meiosis is the mechanism by which the specific chromosome number of each species is maintained across generations in sexually reproducing organisms.

It also increases genetic variability in the population of organisms from one generation to the next, by crossing over. These variations are the raw material of the evolutionary process.