Cell Cycle and Cell Division

Cell Cycle

The cell cycle is the sequence of events that occur in a cell between one cell division and the next. It is a highly regulated process that ensures proper duplication of the genetic material and its distribution into two or more daughter cells.

Cell division is a fundamental process in all living organisms. It is required for:

• Growth: Increase in the number of cells leads to the growth of an organism.
• Repair: Damaged or worn-out tissues are replaced by new cells produced through cell division.
• Reproduction: In unicellular organisms, cell division is the mode of reproduction. In multicellular organisms, it is involved in the formation of gametes for sexual reproduction and the growth of the embryo from a zygote.

The duration of the cell cycle varies depending on the organism and cell type. For example, the cell cycle in yeast takes about 90 minutes, while in human cells (in culture), it is approximately 24 hours. Bacterial cells typically have a much shorter cell cycle.

Phases of Cell Cycle

The cell cycle is divided into two basic phases:

1. Interphase: This is the phase between two successive M phases. It is a period of cell growth and DNA replication. Although often called the 'resting phase', it is metabolically very active.
2. M Phase (Mitosis or Meiosis Phase): This is the actual phase of cell division (nuclear division or karyokinesis) and cytoplasmic division (cytokinesis).

Interphase

Interphase lasts for more than 95% of the duration of the cell cycle. It is further divided into three sub-phases:

• G1 Phase (Gap 1): This is the interval between mitosis and DNA replication. During G1 phase, the cell is metabolically active and continuously grows. It synthesizes proteins and RNA. The cell prepares for DNA replication. The cell decides whether to proceed to the S phase or enter G0 phase.
• S Phase (Synthesis): This is the phase where DNA replication takes place. The amount of DNA per cell doubles (from 2C to 4C if the initial amount is denoted as 2C), but the chromosome number remains the same (if the cell was diploid, 2n, it remains 2n with duplicated chromosomes). In animal cells, DNA replication occurs in the nucleus, and the centriole duplicates in the cytoplasm.
• G2 Phase (Gap 2): During this phase, the cell continues to grow and synthesizes proteins necessary for mitosis, while the DNA replication machinery is completed. The cell prepares for the upcoming M phase.

*(Image shows a pie chart or cyclic diagram representing the cell cycle with G1, S, G2 (collectively Interphase) and M phase, also showing G0 phase)*

G0 Phase (Quiescent Stage)

Some cells in the adult animal do not appear to divide (e.g., heart cells) and many other cells divide only occasionally, as needed to replace cells lost because of injury or cell death. These cells exit the G1 phase and enter an inactive stage called the quiescent stage (G0).

Cells in G0 phase are metabolically active but no longer proliferate unless called upon to do so depending on the requirement of the organism.

After the G2 phase, the cell enters the M phase, which is where the actual division occurs. The M phase includes both karyokinesis (nuclear division) and cytokinesis (cytoplasmic division).

M Phase

The M phase (Mitosis or Meiosis) is the most dramatic period of the cell cycle, involving a major reorganisation of almost all components of the cell. In a human cell cycle of 24 hours, the M phase accounts for only about an hour.

M phase consists of karyokinesis (division of the nucleus) and cytokinesis (division of the cytoplasm).

Karyokinesis itself is divided into four sequential stages: Prophase, Metaphase, Anaphase, and Telophase. These stages are continuous, and their division is for ease of understanding.

Prophase

Prophase is the first stage of karyokinesis following the S and G2 phases of interphase.

Events of Prophase:

• Chromatin condensation: The tangled mass of chromatin fibres condenses to form distinct chromosomes. Each chromosome is visible as two sister chromatids attached at the centromere (formed during S phase).
• Centriole movement: In animal cells, the duplicated centrioles begin to move towards opposite poles of the cell.
• Initiation of the formation of the mitotic spindle, which consists of microtubules that help in cell division.
• The nuclear envelope and the nucleolus start to disintegrate and disappear.

*(Image shows a cell with condensed chromosomes (each with two chromatids), centrioles moving apart, and disappearing nuclear envelope/nucleolus)*

Metaphase

Metaphase is characterised by the complete disappearance of the nuclear envelope.

Events of Metaphase:

• The condensation of chromosomes is completed, and they are clearly visible under the microscope.
• Chromosomes are aligned at the centre of the cell, forming the metaphase plate (equatorial plate). Each chromosome is positioned such that its centromere is at the metaphase plate, and the two sister chromatids are directed towards opposite poles.
• The spindle fibres (microtubules from the poles) attach to the kinetochores (disc-shaped structures present on the sides of the centromere) of the chromosomes. Spindle fibres from one pole attach to the kinetochore of one sister chromatid, and spindle fibres from the opposite pole attach to the kinetochore of the other sister chromatid.

*(Image shows a cell with chromosomes lined up at the equator and spindle fibres attached to kinetochores)*

Anaphase

Anaphase is the stage where the chromosomes are separated and moved to opposite poles.

Events of Anaphase:

• The centromeres split, and the two sister chromatids of each chromosome separate.
• The separated sister chromatids (now considered individual chromosomes) move towards opposite poles of the cell.
• The spindle fibres shorten, pulling the chromosomes towards the poles.
• Chromosomes moving towards the poles appear to trail their arms behind the centromere, giving them characteristic shapes depending on the position of the centromere (V-shaped for metacentric, L-shaped for sub-metacentric, J-shaped for acrocentric, I-shaped for telocentric).

*(Image shows a cell with separating sister chromatids moving towards the poles)*

Telophase

Telophase is the final stage of karyokinesis. It is essentially the reverse of prophase.

Events of Telophase:

• The chromosomes that have reached their respective poles begin to decondense and lose their individuality, turning back into chromatin material.
• A nuclear envelope reforms around the cluster of chromosomes at each pole, forming two daughter nuclei.
• The nucleolus reappears in each daughter nucleus.
• The mitotic spindle apparatus disassembles and disappears.

*(Image shows a cell with chromosomes decondensing at poles, nuclear envelopes reforming, and nucleoli reappearing)*

Cytokinesis

Cytokinesis is the division of the cytoplasm to form two separate daughter cells. It usually begins during late anaphase or telophase.

Mechanism of cytokinesis differs in animal and plant cells:

• Animal Cytokinesis: A cleavage furrow forms in the plasma membrane, usually around the centre of the cell. This furrow deepens and pinches inward, eventually dividing the cytoplasm into two daughter cells.
• Plant Cytokinesis: Plant cells have a rigid cell wall, so cytokinesis occurs by the formation of a cell plate in the centre of the cell. The cell plate grows outwards and eventually fuses with the existing cell wall, dividing the parent cell into two daughter cells. The cell plate is formed from vesicles derived from the Golgi apparatus.

In some organisms, karyokinesis is not followed by cytokinesis, resulting in the formation of a syncytium (a multicellular structure containing multiple nuclei), e.g., liquid endosperm in coconut.

*(Image shows two cells undergoing cytokinesis, one animal cell with cleavage furrow pinching in, and one plant cell with cell plate forming in the middle)*

Significance of Mitosis

Mitosis, also known as equational division, is the type of cell division where the chromosome number of the parent cell is conserved in the daughter cells.

Key significance of mitosis:

• Growth: Mitosis is responsible for the growth of multicellular organisms. It increases the number of cells in the body.
• Cell Repair and Replacement: Cells are constantly being damaged or dying. Mitosis helps in repairing tissues and replacing lost cells, e.g., cells in the upper layer of the epidermis, cells of the lining of the gut, and blood cells are replaced continuously.
• Asexual Reproduction: In some lower organisms (like unicellular organisms, Hydra, yeasts), mitosis is the primary mode of asexual reproduction, producing genetically identical offspring.
• Maintenance of Ploidy Level: Mitosis ensures that the daughter cells have the same number of chromosomes as the parent cell. This is crucial for maintaining genetic stability from one cell generation to the next. A diploid cell (2n) undergoing mitosis produces two diploid daughter cells (2n).
• Restoration of Nucleo-cytoplasmic Ratio: As a cell grows, the ratio between the nucleus and cytoplasm changes. Mitosis helps in restoring this ratio.
• Formation of Multi-cellular Structure from Zygote: A single-celled zygote develops into a multicellular organism through repeated mitotic divisions.

Answer:

Meiosis

Meiosis is a specialised type of cell division that occurs in sexually reproducing organisms. It is called reductional division because it reduces the chromosome number by half.

Meiosis occurs during the formation of gametes (sperm and egg cells) in animals and spore formation in plants.

The purpose of meiosis is twofold:

1. To reduce the diploid ($2n$) chromosome number to haploid ($n$) in the gametes. This is essential so that when two gametes fuse during fertilisation, the resulting zygote restores the diploid number characteristic of the species.
2. To introduce genetic variation among the offspring through processes like crossing over.

Meiosis involves two sequential cycles of nuclear and cell division: Meiosis I and Meiosis II. However, there is only a single cycle of DNA replication, which occurs in the S phase before Meiosis I (just like before mitosis).

If DNA replication occurred before Meiosis II as well, the chromosome number would not be effectively reduced.

Meiosis I

Meiosis I is the reductional division where homologous chromosomes separate, reducing the chromosome number from diploid (2n) to haploid (n).

It consists of Karyokinesis I and Cytokinesis I.

Karyokinesis I:

• Prophase I: This is typically the longest and most complex phase of meiosis. It is further subdivided into five stages:
  • Leptotene: Chromatin condensation begins, making chromosomes visible. Each chromosome consists of two sister chromatids.
  • Zygotene: Homologous chromosomes start pairing up process called synapsis. This pairing results in the formation of a complex structure called the synaptonemal complex. A pair of synapsed homologous chromosomes is called a bivalent or tetrad (because it contains four chromatids).
  • Pachytene: Bivalents become more distinct. Crossing over occurs at this stage. Crossing over is the exchange of genetic material between non-sister chromatids of homologous chromosomes. This enzyme-mediated process is crucial for generating genetic variation. Recombination nodules appear at the sites where crossing over takes place.
  • Diplotene: The synaptonemal complex dissolves. The homologous chromosomes start to separate, but they remain attached at the sites where crossing over occurred. These points of attachment are called chiasmata (singular: chiasma).
  • Diakinesis: The chiasmata terminate towards the ends of the chromosomes (terminalisation of chiasmata). Chromosomes are fully condensed. The nuclear envelope and nucleolus disappear. The spindle fibres start forming.

*(Image shows sequential diagrams of chromosomes condensing, pairing (synapsis/bivalent), crossing over, chiasma formation, and terminalisation)*

• Metaphase I: The bivalents (pairs of homologous chromosomes) align on the equatorial plate (metaphase plate). Each homologous chromosome in a pair is oriented towards opposite poles. Spindle fibres from one pole attach to the kinetochore of one homologous chromosome (containing two chromatids), and spindle fibres from the opposite pole attach to the kinetochore of the other homologous chromosome.

*(Image shows a cell with homologous chromosome pairs lined up at the equator, spindle fibres attached to each chromosome in the pair)*

• Anaphase I: The homologous chromosomes separate and move towards opposite poles. Sister chromatids remain attached at their centromeres. This is the reductional step: the number of chromosomes at each pole is half the diploid number ($n$ chromosomes, each still consisting of two chromatids).

*(Image shows homologous chromosomes moving to opposite poles, with sister chromatids still joined)*

• Telophase I: The homologous chromosomes reach the poles. The chromosomes may decondense somewhat, and a nuclear envelope may form around the chromosomes at each pole (though in many cases, this is brief or absent). The nucleolus may reappear. Cytokinesis (division of cytoplasm) usually follows, resulting in two haploid daughter cells. Each daughter cell now contains $n$ chromosomes, but each chromosome still has two sister chromatids.

*(Image shows a cell dividing into two, with chromosomes (each with two chromatids) at each pole, and a cleavage furrow/cell plate)*

Interkinesis (Interphase II)

The stage between Meiosis I and Meiosis II is called interkinesis or interphase II. It is usually short and does not involve DNA replication. The cell prepares for the second meiotic division.

Meiosis II

Meiosis II is similar to mitosis. It is an equational division where sister chromatids separate, resulting in four haploid daughter cells.

It consists of Karyokinesis II and Cytokinesis II.

Karyokinesis II:

• Prophase II: Meiosis II is initiated immediately after cytokinesis I, often before the chromosomes have fully decondensed. The nuclear envelope (if reformed in Telophase I) disappears, and chromosomes condense again. Spindle fibres form.

*(Image shows two cells (from Meiosis I) with chromosomes condensing and nuclear envelope disappearing)*

• Metaphase II: The chromosomes (each still with two sister chromatids) align at the equatorial plate in each of the two cells. Spindle fibres attach to the kinetochores of sister chromatids.

*(Image shows two cells with chromosomes lined up at the equator)*

• Anaphase II: The centromeres split, and the sister chromatids separate and move towards opposite poles. This is the equational step.

*(Image shows two cells with sister chromatids separating and moving to poles)*

• Telophase II: Chromosomes reach the poles and decondense. Nuclear envelopes reform around the chromosomes at each pole, and nucleoli reappear.

*(Image shows two cells dividing into four, with decondensing chromosomes and reforming nuclei in each, and cytokinesis occurring)*

Cytokinesis II:

Cytokinesis usually occurs concurrently with Telophase II, dividing the cytoplasm of each of the two cells (from Meiosis I) into two, resulting in a total of four haploid daughter cells. Each daughter cell has $n$ chromosomes, and each chromosome consists of a single chromatid.

Overview of Meiosis Outcomes

Starting with a diploid cell (2n) containing chromosomes with replicated DNA (4C content) before Meiosis I:

• After Meiosis I (reductional division): Two haploid cells ($n$) are formed, each containing chromosomes with replicated DNA (2C content). Homologous chromosomes are separated.
• After Meiosis II (equational division): Four haploid cells ($n$) are formed, each containing chromosomes with single chromatids (1C content). Sister chromatids are separated.

*(Image shows a simplified flow chart: Diploid cell (2n, 4C) -> Meiosis I -> Two haploid cells (n, 2C) -> Meiosis II -> Four haploid cells (n, 1C))*

Significance of Meiosis

Meiosis is a crucial process for organisms that reproduce sexually.

Key significance of meiosis:

• Formation of Gametes: Meiosis is essential for the production of haploid gametes (sperm and egg cells in animals, spores in plants). Sexual reproduction involves the fusion of these haploid gametes.
• Maintenance of Chromosome Number: By reducing the chromosome number by half during gamete formation, meiosis ensures that the characteristic diploid chromosome number of a species is restored after fertilisation (fusion of two haploid gametes, $n + n = 2n$). This maintains the genetic stability across generations.
• Introduction of Genetic Variation: Meiosis introduces genetic variation in the population, which is the raw material for evolution. This variation arises primarily through two processes:
  • Crossing Over: Exchange of genetic segments between homologous chromosomes during Prophase I. This shuffles genes between paternal and maternal chromosomes.
  • Independent Assortment: The random orientation and separation of homologous chromosome pairs during Anaphase I. This leads to different combinations of maternal and paternal chromosomes in the daughter cells.

Genetic variation is vital for a population to adapt to changing environments and increases the chances of survival of the species.

Answer:

The organism is diploid with $2n=4$. This means it has 2 pairs of homologous chromosomes.

Let's denote the homologous pairs as Pair 1 and Pair 2. Each pair has one paternal (blue) and one maternal (red) chromosome.

After DNA replication in S phase, before Meiosis I, each chromosome consists of two sister chromatids.

Metaphase I

In Metaphase I, homologous chromosome pairs align at the metaphase plate. There are two possible arrangements for the two pairs:

*(Image shows a cell with metaphase plate. In one diagram, paternal chromosomes of both pairs are on one side of the plate, maternal on the other. In the second diagram, paternal of Pair 1 is on one side, maternal of Pair 1 is on the other, and vice versa for Pair 2. Spindle fibres attached to the whole homologous chromosome)*

Arrangement 1 (Left): Paternal chromosomes of both pairs on one side, maternal on the other.

Arrangement 2 (Right): Paternal chromosome of Pair 1 and Maternal chromosome of Pair 2 on one side, and vice versa on the other.

These different arrangements lead to independent assortment during Anaphase I.

Metaphase II

Meiosis II starts with the two cells formed after Meiosis I. Let's consider the cells resulting from Arrangement 1 in Metaphase I. The cell on the left pole in Anaphase I would get the two paternal chromosomes (each with 2 chromatids). The cell on the right pole would get the two maternal chromosomes (each with 2 chromatids).

In Metaphase II, the chromosomes (which are haploid in number, $n=2$, but still consist of two chromatids) align at the metaphase plate in each of these two cells. The chromosomes align individually, not in pairs like in Metaphase I.

*(Image shows two cells in Metaphase II. In the first cell, the two paternal chromosomes (from Meiosis I) are lined up at the equator. In the second cell, the two maternal chromosomes (from Meiosis I) are lined up at the equator. Spindle fibres attached to kinetochores of sister chromatids)*

Note: If we had considered Arrangement 2 from Metaphase I, the chromosomes aligning in Metaphase II would be mixed (e.g., Paternal of Pair 1 and Maternal of Pair 2 in one cell, and Maternal of Pair 1 and Paternal of Pair 2 in the other cell).

In Anaphase II, the sister chromatids will separate, leading to four haploid cells ($n=2$) with single chromatid chromosomes, with different combinations of paternal and maternal chromosomes depending on the Metaphase I alignment and crossing over.