Comprehensive Study Notes on Cell and Nuclear Division (IB Biology D2.1)

Core Principles of Cell Division

Cell Division Defined:
- Cell division is the biological process by which a parent cell (frequently designated as a mother cell) divides to produce two daughter cells.
- This universal mechanism occurs across all living organisms to maintain genetic continuity and cellular propagation.
Essential Curricular Themes and Guiding Questions:
- Overarching Biological Theme: Continuity and Change.
- Biological Level of Organisation: Cells.
- Primary Inquiry (Clonal Propagation): How can large numbers of genetically identical cells be produced?
- Primary Inquiry (Gametic Diversity): How do eukaryotes produce genetically varied cells that can develop into gametes?
- Evolutionary and Growth Inquiries:
  - What physiological and cellular processes support the somatic growth of organisms?
  - How does the genomic variation generated through sexual reproduction supply the raw material for evolutionary change?

Cytokinesis in Animal and Plant Cells

Mechanisms of Cytokinesis:
- Cytokinesis represents the physical splitting of the parent cell cytoplasm between two daughter cells following the completion of nuclear division (mitosis or meiosis).
- The structural differences between eukaryotic kingdoms dictate distinct mechanical pathways for cytoplasmic partitioning.

Cytokinesis in Animal Cells:
- A contractile ring composed of actin and myosin protein microfilaments assembles circumferentially around the equator of the dividing parent cell.
- Actin and myosin are anchored directly to the internal face of the plasma membrane.
- The dynamic contraction of this ring constricts the cell inwards, generating an invagination designated as the cleavage furrow.
- The cleavage furrow progressively deepens inward until the opposed plasma membranes touch, undergo membrane fusion, and cleave the parent cell into two distinct, membrane-bound daughter cells.
Cytokinesis in Plant Cells:
- The presence of a rigid cellulose cell wall prevents the physical constriction of the cell membrane via a contractile ring.
- Instead, the Golgi apparatus synthesizes and secretes carbohydrate-filled membrane vesicles.
- These Golgi vesicles are transported along microtubules toward the equatorial plate (metaphase plate) of the cell.
- The vesicles align and coalesce at the equator to form a continuous, membrane-bound structure known as the cell plate.
- The outer membranes of the coalesced vesicles fuse with the pre-existing lateral plasma membranes of the parent cell, establishing two continuous, separated protoplasts.
- Pectins and cellulose are subsequently secreted into the internal lumen of the newly formed cell plate, building the primary cell wall and middle lamella between the two daughter cells.

Organelle Partitioning and Asymmetric Cytokinesis

Equal Cytokinesis and Organelle Partitioning:
- In the majority of somatic cellular divisions, cytokinesis divides the cytoplasm symmetrically, yielding two daughter cells of equivalent volumetric dimensions.
- Both daughter cells must inherit at least one copy of every essential organelle that cannot be assembled de novo from basic biochemical components.
- Mitochondrial and Chloroplast Inheritance:
  - Mitochondria and chloroplasts contain their own circular DNA genomes and $70\text{S}$ ribosomes, reproducing semi-autonomously via binary fission independently of the host cell cycle.
  - A cell that fails to receive at least one pre-existing mitochondrion or chloroplast during cytokinesis possesses no template to synthesize replacement organelles, resulting in non-viable or metabolically incompetent cells.
Unequal Division of the Cytoplasm:
- Specific developmental pathways require asymmetric cytokinesis, where cytoplasm is deliberately partitioned unequally between daughter cells.
- Budding in Yeast (Saccharomyces cerevisiae):
  - A specialized mode of asexual reproduction wherein a daughter cell emerges as a small outpocketing (bud) from the parent cell.
  - The nucleus undergoes mitotic division, and one daughter nucleus migrates into the protruding bud.
  - Asymmetric cytokinesis pinches off the bud, leaving a small, viable daughter cell alongside a substantially larger parent cell possessing the preponderance of the original cytoplasm.

Scanning electron micrograph of budding yeast cells

Oogenesis in Human and Animal Females:
- The biological process of female gamete (ovum) synthesis involving highly asymmetrical cytokinesis during both Meiosis I and Meiosis II.
- The meiotic divisions concentrate nearly all nutrients, cytoplasmic enzymes, ribosomes, and organelles into a single large, mature ovum.
- The remaining genetic material is relegated to miniature, non-functional daughter cells termed polar bodies, which subsequently degenerate.
- This asymmetric investment ensures the zygote inherits sufficient cytoplasmic volume and energetic reserves to sustain embryonic development prior to implantation.

Roles and Distinctions of Mitosis and Meiosis

Nuclear Division Preceding Cell Division:
- Mitosis and meiosis represent specialized mechanisms of eukaryotic nuclear division, distinct from the physical separation of the cytoplasm (cytokinesis).
- Nuclear division must precede cytokinesis to prevent the formation of anucleate cells (cells lacking a nucleus and genetic material).
Biological Roles of Mitosis:
- Mitosis is an equational nuclear division producing two genetically identical daughter nuclei with an identical chromosome count ( $2n \rightarrow 2n$ ).
- Organismal Growth and Morphogenesis: Facilitates the expansion of cell numbers from a single-celled zygote through all stages of embryological development to an adult organism.
- Tissue Repair and Somatic Replacement: Enables regeneration and maintenance by generating healthy cells to replace senescent, apoptotic, or mechanically damaged tissues.
- Asexual Reproduction: Utilized by unicellular eukaryotes (e.g., Amoeba, Paramecium) and specific multicellular organisms for clonal vegetative reproduction.
Biological Roles of Meiosis:
- Meiosis is a specialized reduction division producing four genetically distinct daughter nuclei, each containing half the chromosome complement of the original diploid parent nucleus ( $2n \rightarrow n$ ).
- Gametic Production: Generates haploid sperm and ova in animals, and haploid spores in plants and fungi.
- Maintenance of Ploidy Across Generations: Halves the ploidy level so that subsequent sexual fertilization restores the diploid ( $2n$ ) chromosome number in the zygote.

Human sexual life cycle illustrating mitosis and meiosis

Chromosome Structure, Condensation, and Movement

Prerequisite DNA Replication:
- DNA replication is an obligatory prerequisite occurring during the S phase of interphase before both mitosis and meiosis.
- Following semiconservative replication, each chromosome consists of two elongated, identical DNA duplexes termed sister chromatids, which remain physically conjoined at a specialized constriction called the centromere.
- Chromosome Counting Nomenclature:
  - An unduplicated chromosome contains a single double-stranded DNA molecule and counts as one chromosome.
  - A duplicated chromosome consists of two sister chromatids joined at one centromere and is still counted as a single chromosome.
  - Once sister chromatids are cleaved at their centromere during anaphase, each chromatid is classified as an independent, single-stranded daughter chromosome.

Comparison of an unduplicated chromosome and a duplicated chromosome with sister chromatids

Chromatin Organization and Supercoiling:
- Throughout interphase, nuclear DNA persists in an uncoiled, diffuse state known as chromatin, which is transcriptionally accessible but invisible under standard light microscopy.
- During early nuclear division (prophase of mitosis, prophase I and II of meiosis), chromatin undergoes condensation via supercoiling to facilitate orderly segregation without entangling or mechanical shearing.
- Nucleosome Architecture:
  - The double-helical DNA strand wraps tightly around an octamer of basic histone proteins to construct structural subunits called nucleosomes.
  - Nucleosomes pack together and coil extensively to generate dense, microscopically visible chromosomes comprising sister chromatids.

DNA packing into nucleosomes and higher-order chromosome structures

Microtubule-Mediated Chromosome Segregation:
- The mitotic and meiotic spindle apparatus consists of organized polymers of alpha- and beta-tubulin forming microtubules.
- Microtubules attach directly to specialized protein assemblies termed kinetochores, which reside at the centromere region of each chromosome.
- Specialized microtubule motor proteins embedded within the kinetochore complex facilitate directional movement along the spindle fibers toward the opposing spindle poles during anaphase, coupled with microtubule depolymerization.

Kinetochore microtubule and motor protein moving a chromosome

Stages of Mitosis and Microscopic Identification

Mitotic Progression:
- Mitosis proceeds through four continuous, sequentially ordered phases: prophase, metaphase, anaphase, and telophase.

Diagram of the successive stages of mitosis

*   **Prophase**:
    *   Chromatin supercoils and condenses into discrete, visible chromosomes, each composed of two sister chromatids bound at the centromere.
    *   The nucleolus disappears and the nuclear envelope disintegrates into membrane fragments.
    *   Centrosomes migrate toward opposing cellular poles, polymerizing microtubules to establish the mitotic spindle.
    *   Kinetochores assemble at centromeres and attach to radiating spindle microtubules.
*   **Metaphase**:
    *   Kinetochore microtubules exert mechanical tension, moving chromosomes to the equatorial plane of the cell.
    *   Chromosomes align in a linear array along the metaphase plate.
*   **Anaphase**:
    *   Centromeric cohesin proteins are cleaved, enabling the separation of sister chromatids.
    *   Kinetochore motor proteins transport the newly individualized single-stranded daughter chromosomes toward opposite cellular poles.
    *   Simultaneously, polar microtubules push against one another to elongate the cell.
*   **Telophase**:
    *   Daughter chromosomes arrive at the respective cellular poles.
    *   The chromosomes begin to decondense and uncoil, reverting into diffuse chromatin.
    *   Nuclear envelopes assemble around each distinct set of chromosomes, and nucleoli reappear.
    *   The mitotic spindle disassembles completely, marking the completion of nuclear division as cytokinesis initiates.

Microscopic Phase Identification:
- Analysis of mitotic tissue preparations (such as Allium root tip meristems viewed at a magnification of $2200\times$ ) enables the discrimination of specific mitotic phases alongside non-dividing interphase cells.

Micrograph showing plant cells at different stages of the cell cycle and mitosis

Image Analysis Reference Guide (Labels A through H):
- Label A: Prophase (distinct, thickened, dark-staining chromosome strands visible within a spherical, intact nuclear boundary).
- Label B: Non-mitotic cell / Interphase (homogeneous, granular nuclear staining; intact nucleolus and nuclear envelope visible; lack of distinct chromosome threads).
- Label C: Anaphase (two distinct, symmetric clusters of sister chromatids migrating toward opposite cellular margins).
- Label D: Metaphase (condensed chromosomes tightly aligned across the equatorial midline of the cell).
- Label E: Anaphase (V-shaped chromatid arms visibly pulled toward opposing poles by spindle fibers).
- Label F: Anaphase (active chromosomal separation and migration toward cellular poles).
- Label G: Non-mitotic cell / Interphase (prominent, intact, round nucleus displaying diffuse chromatin).
- Label H: Telophase (two dense chromatin aggregates located at opposite poles, with a reforming cell plate emerging at the midline).

Meiosis as a Reduction Division

Ploidy Definitions and Concepts:
- Diploid ( $2n$ ): A cellular state characterized by nuclei possessing two complete sets of chromosomes, organized as homologous pairs (one set inherited maternally, one paternally).
- Haploid ( $n$ ): A cellular state characterized by nuclei containing a single complete set of unpaired chromosomes.
- Homologous Chromosomes: Pairs of chromosomes of identical length, centromere location, and gene order (loci), which may nevertheless carry differing alleles of those genes.

Homologous chromosomes before and after replication

Bivalent Formation and Crossing Over:
- During early meiosis, homologous chromosomes align lengthwise in a process termed synapsis to form paired structures known as bivalents (or tetrads, containing four chromatids).
- During synapsis, non-sister chromatids break and rejoin at points called chiasmata, exchanging reciprocal chromosomal segments in the process of crossing over.

Synapsis of homologous chromosomes forming a bivalent

Two Rounds of Meiotic Segregation:
- Meiosis consists of two sequential nuclear divisions preceded by a single round of DNA replication, ultimately generating four haploid nuclei from one diploid progenitor cell.

Overview of nuclear divisions in Meiosis I and Meiosis II

Meiosis I (Reductional Division: Segregation of Homologous Pairs):
- Prophase I: Chromatin condenses into visible chromosomes. Homologous chromosomes undergo synapsis to assemble into bivalents. Crossing over occurs between non-sister chromatids, shuffling alleles. The nuclear envelope breaks down and spindle fibers form.
- Metaphase I: Spindle microtubules align bivalents along the equatorial plate. The orientation of maternal and paternal homologs toward either pole is random (independent assortment).
- Anaphase I: Spindle fibers pull homologous chromosome pairs apart toward opposite poles. Centromeres remain intact, keeping sister chromatids physically joined.
- Telophase I: Chromosomes arrive at the poles and uncoil; nuclear envelopes may reassemble. Cytokinesis follows, producing two haploid ( $n$ ) cells where each chromosome is still composed of duplicated sister chromatids.
Meiosis II (Equational Division: Segregation of Sister Chromatids):
- Prophase II: Chromatin condenses once again into visible sister chromatids within both haploid daughter cells. Centrioles migrate to form new spindles positioned perpendicular to the plane of Meiosis I. Microtubules attach to kinetochores.
- Metaphase II: Individual chromosomes align single-file across the equatorial plate (distinct from the paired bivalents in Metaphase I).
- Anaphase II: Centromeres split; kinetochore motor proteins pull sister chromatids apart into single-stranded chromosomes that migrate to opposite poles.
- Telophase II: Single-stranded chromosomes arrive at the poles and decondense. Nuclear envelopes reassemble around the four sets of chromosomes. Cytokinesis divides the cytoplasm, producing four genetically non-identical haploid ( $n$ ) gametes.

Chromosomal Non-Disjunction and Down Syndrome

Mechanisms of Non-Disjunction:
- Non-disjunction is the failure of homologous chromosome pairs or sister chromatids to separate correctly during nuclear division.
- Non-Disjunction in Anaphase I: Homologous chromosomes in a bivalent fail to segregate to opposite poles. Both homologs migrate to the same daughter cell, resulting in two gametes carrying an extra chromosome ( $n+1$ ) and two gametes missing a chromosome ( $n-1$ ).
- Non-Disjunction in Anaphase II: Sister chromatids fail to separate. One daughter cell receives both chromatids while the other receives none, resulting in one $n+1$ gamete, one $n-1$ gamete, and two normal $n$ gametes.

Diagram of non-disjunction occurring during meiosis

Consequences of Aneuploidy and Trisomy:
- When an abnormal gamete carrying an extra chromosome ( $n+1$ ) fuses with a normal gamete ( $n$ ) during fertilization, the resulting zygote possesses three homologous copies of that chromosome, an aneuploid condition termed trisomy ( $2n+1$ ).
- When an $n-1$ gamete fuses with an $n$ gamete, monosomy ( $2n-1$ ) occurs, which is frequently lethal during embryogenesis.
Down Syndrome (Trisomy 21):
- Down syndrome is defined cytogenetically by the presence of three copies of chromosome 21, resulting in a somatic chromosome complement of 47 chromosomes instead of the normal 46.
- The vast majority of cases arise due to maternal non-disjunction occurring during oogenesis, producing an ovum with two copies of chromosome 21.
- Fertilization by a normal sperm possessing one copy of chromosome 21 yields a zygote with three copies ( $2n+1=47$ ).

Meiosis as a Generator of Genetic Variation

Crossing Over During Prophase I:
- The breakage and reciprocal exchange of DNA segments between non-sister chromatids of a homologous bivalent breaks ancestral linkage groups.
- This physical exchange recombines maternal and paternal alleles along a single chromatid, producing novel combinations of alleles not found in either parent.
Independent Assortment and Random Orientation During Metaphase I:
- Bivalents align along the cell equator with their maternal and paternal homologs oriented randomly toward either cellular pole.
- The poleward orientation of one homologous pair is entirely independent of the orientation of all other homologous pairs.
- For a species with a haploid chromosome count of $n$ , the number of possible gametic chromosome combinations resulting exclusively from independent assortment is calculated as: $\text{Combinations} = 2^n$
- In humans, where $n = 23$ : $2^{23} = 8{,}388{,}608\text{ distinct chromosomal combinations}$
Evolutionary Implications:
- Crossing over coupled with independent assortment generates a near-infinite array of unique gametic genotypes.
- Subsequent random fertilization between genetically diverse sperm and egg populations maximizes genomic variation within a population, providing the phenotypic breadth required for natural selection and adaptive evolution.

Cell Proliferation in Multicellular Organisms (HL)

Concept of Cell Proliferation:
- Cell proliferation is the coordinated process whereby cells grow and divide via the cell cycle to produce two daughter cells.
- This exponential expansion ( $1 \rightarrow 2 \rightarrow 4 \rightarrow 8 \rightarrow \dots \rightarrow 2^n$ ) serves as the primary mechanism for biological growth, tissue repair, and ongoing cellular replacement.
Biological Examples of Proliferation:
- Early Embryonic Cleavage: Following fertilization, the mammalian or animal zygote undergoes rapid proliferative cycles of mitosis and cytokinesis without intervening growth to form a blastula.
- Plant Meristems: Meristems are localized reservoirs of undifferentiated plant stem cells (e.g., apical and lateral meristems) that undergo continuous proliferation, subsequently differentiating into vascular, ground, and dermal tissues to drive primary and secondary plant growth.
- Routine Tissue Renewal (Epidermis):
  - Epithelial cells of the skin are constantly sloughed off and lost from the superficial stratum corneum.
  - Stem cells residing in the basal layers continually proliferate to replenish lost epidermal layers.
- Wound Healing: In response to mechanical injury, local paracrine signaling induces rapid proliferation of epithelial cells and fibroblasts to regenerate tissue continuity and heal the lesion.

The Cell Cycle and Interphase Dynamics (HL)

Phases of the Eukaryotic Cell Cycle:
- The eukaryotic cell cycle comprises three sequential master events: Interphase, Mitosis (nuclear division), and Cytokinesis (cytoplasmic division).

Interphase as a Metabolically Active State:
- A cell spends approximately 90% of its lifetime in interphase, which is an energetically demanding, highly active metabolic interval characterized by cellular respiration, biosynthesis, and growth.
- Gap 1 ( $G_1$ Phase):
  - Follows cytokinesis; the cell undergoes rapid physical growth and volumetric expansion.
  - Marked by intense protein synthesis (transcription and translation) to synthesize structural proteins and enzymatic machinery.
  - Biogenesis of non-autonomous organelles occurs, alongside the intake of nutrients.
- Synthesis (S Phase):
  - The cell conducts complete semiconservative replication of its nuclear genomic DNA.
  - Chromosomes duplicate, transitioning from single-stranded DNA structures into paired sister chromatids joined at their centromeres.
- Gap 2 ( $G_2$ Phase):
  - The final preparatory window before entering mitosis.
  - The cell undergoes further growth, replicates centrosomes, synthesizes mitotic spindle tubulin proteins, and scans replicated DNA for errors or lesions.
Organelle Proliferation During Interphase:
- Chloroplasts and mitochondria multiply during the $G_1$ and $G_2$ phases.
- Because they divide by autonomous binary fission, their numbers expand prior to nuclear division to guarantee that cytokinesis allocates adequate numbers to each daughter cell.

Molecular Control of the Cell Cycle by Cyclins (HL)

Cyclins and Cyclin-Dependent Kinases (CDKs):
- Cyclins are a conserved family of four regulatory proteins whose intracellular concentrations fluctuate cyclically throughout distinct phases of the cell cycle.
- Cyclins do not possess intrinsic enzymatic activity; instead, they bind to and activate specific enzymes termed Cyclin-Dependent Kinases (CDKs).
- Active cyclin-CDK complexes act as functional kinases, transferring phosphate groups from ATP onto designated target proteins via phosphorylation.
- Phosphorylation triggers conformational changes in target proteins, orchestrating downstream metabolic cascades that drive the cell into the next cycle phase.
Cyclin Concentration Dynamics Across Phases:
- Cyclin D: Accumulates gradually during early $G_1$ , sustains high levels through S and $G_2$ , and drops during mitosis; regulates initial entry and overall advancement across the cycle.
- Cyclin E: Peaks sharply at the $G_1/S$ transition, facilitating the initiation of DNA synthesis and centrosome duplication.
- Cyclin A: Accumulates during S phase to regulate DNA replication progression, sustaining elevation into $G_2$ before degrading in early mitosis.
- Cyclin B: Rises through $G_2$ , peaking at the onset of mitosis; activates CDK1 to drive chromosomal condensation, nuclear envelope breakdown, and mitotic spindle assembly.

Cyclin concentration fluctuations throughout the cell cycle phases

Cell Cycle Checkpoints and Threshold Control:
- Progression through the cell cycle is restricted at specific regulatory checkpoints; transition past a checkpoint requires that the concentration of a specific cyclin reaches a critical threshold level.

Key checkpoints regulating transitions in the cell cycle

$G_1$ Checkpoint (Restriction / Cell Cycle Initiation Checkpoint):
- Positioned near the conclusion of $G_1$ .
- Assesses cell size, nutritional status, growth factors, and DNA integrity.
- If conditions are unfavorable or growth signals are absent, the cell exits the active cycle and enters a non-dividing, quiescent resting state designated as $G_0$ .
$G_2$ Checkpoint ( $G_2$ to M Transition Checkpoint):
- Positioned at the boundary between $G_2$ and Mitosis.
- Monitors cell size and verifies the accurate, complete replication of the genome, checking for DNA mutations or un-replicated strands before permitting mitotic entry.
M-Spindle Checkpoint (Metaphase-to-Anaphase Transition Checkpoint):
- Operates during metaphase of mitosis.
- Monitors the mechanical tension and bipolar attachment of all kinetochores to spindle microtubules, preventing anaphase separation until every chromosome is aligned properly at the equator.

Genetic Control, Oncogenesis, and Tumorigenesis (HL)

Mutations in Cell Cycle Regulatory Genes:
- A mutation is defined as any physical alteration in the nucleotide base sequence of DNA or viral genomes.
- Uncontrolled cell division results when mutations disrupt the fine-tuned genetic networks that govern cell cycle checkpoints.
Tumour Suppressor Genes:
- Genes whose normal protein products function as biological brakes, inhibiting cell proliferation, repairing damaged DNA, and promoting apoptosis (programmed cell death) when genetic lesions cannot be repaired.
- Loss-of-function mutations in tumour suppressor genes eliminate these inhibitory constraints, permitting damaged or uncontrolled cells to undergo unregulated proliferation.
Proto-Oncogenes and Oncogenes:
- Proto-oncogenes: Highly conserved normal genes that code for proteins responsible for stimulating cell division, cellular growth, and survival pathways.
- Oncogenes: Mutated, hyperactive versions of proto-oncogenes that stimulate continuous, autonomous cell division independent of normal growth factors, leading directly to tumour development.
Tumour Classification and Metastasis:
- A tumour is an abnormal mass or swelling of tissue caused by aberrant, deregulated cell proliferation.
- Primary Tumour: The original, initial site of abnormal cellular transformation and tumour growth within a tissue.
- Benign Tumours:
  - Non-cancerous growths that display slow rates of cellular proliferation.
  - Cells remain localized and encapsulated, lacking the ability to invade neighboring tissues or metastasize to distant body sites.

Diagrammatic representation of a benign tumor

Malignant Tumours:
- Cancerous growths characterized by rapid, uncontrolled cell division and cellular atypia.
- Possess the enzymatic and migratory capacity to invade adjacent normal tissue parenchyma.

Diagrammatic representation of a malignant tumor invading tissue

Metastasis:
- The process by which malignant cells detach from the primary tumour, intravasate into vascular or lymphatic networks, circulate through the body, and extravasate into distant organs.
Secondary Tumour: A systemic, distant malignant growth established by metastatic cells that traveled from the primary tumour site.

Mitotic Index in Clinical and Biological Analysis (HL)

Mathematical Definition of Mitotic Index:
- The mitotic index is a quantitative metric representing the proportion of cells actively undergoing mitosis relative to the total number of cells observed within a given histological field: $\text{Mitotic Index} = \frac{\text{Number of cells undergoing mitosis}}{\text{Total number of cells observed}}$
- When expressed as a percentage, the formula is: $\text{Mitotic Index (\%)} = \left(\frac{\text{Number of cells in mitosis}}{\text{Total number of cells}}\right) \times 100$
Diagnostic Significance in Oncology:
- While high mitotic indices are physiologically normal in rapidly dividing growth zones (e.g., plant root meristems, early blastomeres), an abnormally elevated mitotic index in adult animal tissues serves as a strong clinical indicator of cancerous transformation.
- Histopathologists utilize the mitotic index to determine the histological grade of tumours, predict disease progression, and assess the responsiveness of malignant cells to antiproliferative chemotherapeutic agents.
Quantitative Micrograph Case Study (Allium Root Tip):
- An analysis of an onion (Allium) root tip meristem micrograph provides a model dataset for determining mitotic index.

Micrograph of onion root tip cells used to calculate the mitotic index

Observed Parameters:
- Total population of cells counted ( $N_{\text{total}}$ ): $91$
- Number of cells displaying condensed, mitotic chromosomes ( $N_{\text{mitosis}}$ ): $26$
Calculation: $\text{Mitotic Index} = \frac{26}{91} \approx 0.2857 \approx 0.29$
Percentage Calculation: $\text{Mitotic Index (\%)} = 0.2857 \times 100 = 28.57\%$

Standard and Higher Level Terminology Directory

Core Concepts (SL & HL):
- Parent Cell (Mother Cell): A mature cell that divides to generate two daughter cells.
- Daughter Cell: One of the two genetically defined cells generated via cell division.
- Cytokinesis: The physical division of the parent cell cytoplasm between daughter cells.
- Cleavage Furrow: The invaginating groove formed by the contraction of an actin-myosin ring during animal cell cytokinesis.
- Cell Plate: The precursor structure formed by the coalescence of Golgi-derived carbohydrate vesicles along the plant cell equator during plant cytokinesis.
- Oogenesis: The formation of female gametes (ova) involving asymmetric cytokinesis to yield one functional ovum and polar bodies.
- Budding: A form of asexual reproduction (as seen in yeast) where a small daughter cell buds off a larger parent cell.
- Mitosis: An equational nuclear division producing two genetically identical daughter nuclei.
- Meiosis: A reductional nuclear division producing four genetically varied haploid daughter nuclei.
- Anucleate Cell: A defective cell lacking a nucleus, resulting when cytokinesis occurs without prior nuclear division.
- DNA Replication: The semiconservative synthesis of two identical copies of a DNA molecule prior to division.
- Chromosome: A distinct structure composed of condensed DNA and histone proteins carrying genetic information.
- Sister Chromatids: Two identical copies of a duplicated chromosome conjoined at the centromere.
- Centromere: The specialized DNA-protein region of a chromosome where sister chromatids are joined and kinetochores assemble.
- Condensation: The process of chromatin supercoiling into compact, visible chromosomes during prophase.
- Histone Proteins: Alkaline proteins around which eukaryotic DNA winds to form nucleosome subunits.
- Nucleosome: The basic structural unit of eukaryotic chromatin, consisting of DNA wrapped around an octamer of histone proteins.
- Spindle Fibres: Microtubule polymers that extend from cellular poles to organize and move chromosomes during division.
- Kinetochores: Protein complexes assembled on chromosomal centromeres that serve as attachment points for spindle microtubules.
- Microtubule Motors: Dynamic motor proteins located on kinetochores that move chromosomes along spindle microtubules via ATP hydrolysis.
- Prophase: The initial stage of mitosis characterized by chromosome condensation, spindle assembly, and nuclear envelope breakdown.
- Metaphase: The mitotic stage wherein chromosomes align along the equatorial metaphase plate.
- Anaphase: The mitotic phase where centromeres cleave and sister chromatids are pulled to opposite poles.
- Telophase: The final mitotic phase where chromosomes arrive at the poles, decondense, and nuclear envelopes reform.
- Reduction Division: A nuclear division (Meiosis I) that halves the chromosome number from diploid ( $2n$ ) to haploid ( $n$ ).
- Haploid ( $n$ ): A cell possessing one single complete set of chromosomes.
- Diploid ( $2n$ ): A cell possessing two complete homologous sets of chromosomes.
- Homologous Chromosomes: Chromosomes of identical morphology and gene loci, inherited respectively from maternal and paternal parents.
- Bivalent (Tetrad): The four-chromatid structure formed by the pairing of two homologous chromosomes during synapsis in Prophase I.
- Crossing Over: The physical exchange of genetic material between non-sister chromatids of a bivalent at chiasmata.
- Zygote: The diploid cell resulting from the fertilization of a haploid egg by a haploid sperm.
- Non-Disjunction: The failure of homologous chromosome pairs or sister chromatids to separate properly during division.
- Down Syndrome (Trisomy 21): A genetic condition caused by non-disjunction resulting in three copies of chromosome 21 ( $2n+1=47$ ).
- Independent Assortment: The random orientation and segregation of maternal and paternal homologous chromosomes along the metaphase plate.
Higher Level Concepts (HL Only):
- Cell Proliferation: The active cellular process combining growth and division to generate an exponential increase in cell numbers.
- Meristem: Undifferentiated plant tissue located in growing tips capable of continuous cell division and proliferation.
- Interphase: The metabolically active period of the cell cycle between nuclear divisions, comprising $G_1$ , S, and $G_2$ phases.
- $G_1$ Phase: The initial growth and metabolic expansion phase of interphase following cytokinesis.
- S Phase: The interphase interval during which nuclear genomic DNA is synthesized and replicated.
- $G_2$ Phase: The final preparatory interphase phase wherein the cell expands and synthesizes mitotic proteins.
- Cyclins: Regulatory proteins whose cyclically fluctuating concentrations govern movement through cell cycle checkpoints.
- Cyclin-Dependent Kinases (CDKs): Protein kinases that, when bound by cyclins, phosphorylate target proteins to drive cell cycle progression.
- Tumour Suppressor Gene: A gene that codes for proteins that restrain cell proliferation and prevent tumor development.
- Proto-Oncogene: A normal regulatory gene that promotes cell growth and division, capable of mutating into an oncogene.
- Oncogene: A mutated or overexpressed gene that drives unregulated cell proliferation, leading to cancer.
- Tumour: An abnormal, circumscribed mass of tissue resulting from unregulated, autonomous cell proliferation.
- Primary Tumour: The initial original neoplasm arising at the primary anatomical site of transformation.
- Secondary Tumour: A distant metastatic colony established by malignant cells that detached from a primary tumour.
- Metastasis: The systemic spread of malignant cancer cells from a primary tumour to secondary locations via blood or lymph.
- Cancer: A disease characterized by the uncontrolled, invasive proliferation of malignant cells capable of metastasis.
- Benign Tumour: A slow-growing, encapsulated non-cancerous neoplasm that does not invade tissue or metastasize.
- Malignant Tumour: A fast-growing cancerous neoplasm that invades neighboring tissues and undergoes systemic metastasis.
- Mitotic Index: The mathematical ratio of dividing cells to total observed cells within a given tissue sample.