Structure of Chromosomes, Cell Cycle, and Cell Division Notes

Overview of Cell Division and Basic Biology

• Fundamental Characteristic of Life: Cell division is a basic requirement for the perpetuation of life across generations.
• Scale of Occurrence: It occurs in simple organisms such as amoeba, as well as complex organisms like humans, giant elephants, and tall coconut trees.
• Role of Chromosomes: The most significant events in cell division involve chromosomes. During mitosis, duplicated chromosomes are evenly distributed into daughter cells.
• Consistency: All body cells resulting from mitotic divisions contain the same type and number of chromosomes, ensuring normal functioning and life of the organism.

What are Chromosomes?

• Visibility: In a normal unstained living cell, the nucleus may appear empty under a light microscope. However, when stained with specific dyes, structures become visible.
• Composition: The nucleus contains DNA organized into discrete units called chromosomes. Each chromosome consists of one long DNA molecule associated with proteins.
• Chromatin: This complex of DNA and protein is called chromatin. Under an electron microscope (when not dividing), it appears as very long, thin, darkly stained fibers.
• Condensation: As a cell prepares to divide, chromatin fibers coil and condense to become thick enough to be distinguished as separate chromosomes.
• Etymology: The name "chromosome" is derived from the Greek words chroma (meaning colored) and soma (meaning body), due to their ability to pick up dyes.
• Formal Definition: Chromosomes are highly coiled, ribbon-like structures formed by the condensation of chromatin fibers during cell division.

Discovery and Key Scientists

• Walther Flemming (1882): A German scientist who first studied chromosomes in the rapidly dividing cells of salamander larvae (an amphibian). He observed minute threads dividing lengthwise and termed the process "mitosis" (literally meaning "thread").
• Rosalind Franklin (1953): First studied the shape of the DNA molecule.
• James Watson and Francis Crick (1953): Worked out the double-stranded helical structure of DNA. They were awarded the Nobel Prize in 1962 for this discovery.

Chemical Composition and Structure of Chromatin

• Substances in Chromatin:     * DNA (Deoxyribonucleic acid): Approximately $40\%$.     * Histones (a specific type of protein): Approximately $60\%$.

Molecular Structure of DNA

• Macromolecule: A single DNA molecule is very large and composed of two complementary strands wound in a double helix.
• Nucleotides: Each strand is made of repeating units called nucleotides. A nucleotide consists of:     1. Phosphate group.     2. Sugar (Pentose/Ribose).     3. A nitrogenous base.
• Nitrogenous Bases: There are four types found in DNA: Adenine (A), Guanine (G), Cytosine (C), and Thymine (T).
• Pairing Rules: Bases extend inwards and join via hydrogen bonds to complementary bases on the opposite strand:     * Adenine (A) pairs with Thymine (T) with two hydrogen bonds ($A=T$).     * Guanine (G) pairs with Cytosine (C) with three hydrogen bonds ($G \equiv C$).
• Structural Analogy: The sugar and phosphate form the "rails" of a ladder, while the nitrogenous bases form the "rungs."

Histones and Nucleosomes

• Packaging: Histones help in coiling and packaging DNA. The DNA strand winds around a core of eight histone proteins, known as a histone octamer.
• Nucleosome: Each complex of DNA and the histone octamer is a nucleosome.
• Scale: Each human cell contains roughly $2\,m$ of DNA if stretched. Since the nucleus is only about $6\,\mu m$ in diameter, the DNA must be condensed through coiling and supercoiling, similar to a telephone cord.
• Quantity: A single human chromosome can contain about a million nucleosomes.

Structure of a Chromosome

• Chromatids: At the start of cell division, a condensed chromosome consists of two "sister chromatids."
• Centromere: The sister chromatids are joined at a small constricted region called the centromere. Its location is specific to each chromosome.
• Function of Centromere:     * Attaches the chromosome to spindle fibers during division.     * During Anaphase, as spindle fibers contract, the centromere helps in separating sister chromatids toward opposite poles.
• Post-Division: After division, chromatids (now called chromosomes) decondense back into fine chromatin fibers. The number of chromatin fibers in a nucleus equals the number of chromosomes that appeared during division.

Genes and Heredity

• Definition: Genes are specific sequences of nucleotides on a chromosome that encode particular proteins expressed as physical features of the body.
• Function: They are the units of heredity transferred from parents to offspring, responsible for specific characteristics.
• Non-functional DNA: Most regions between genes (about $99\%$ of total DNA) are non-functional and show high variation between individuals.
• DNA Fingerprinting: This technique utilizes variations in non-functional DNA for identification, establishing paternity/maternity, and criminal investigations (using biological evidence like blood, hair, or skin).

The Need for New Cells

1. Growth: Organisms start as a single cell (zygote) which divides repeatedly to form tissues and organs. (Example: A 4-day-old human embryo has $16$ cells resulting from four divisions: $1 \rightarrow 2 \rightarrow 4 \rightarrow 8 \rightarrow 16$).
2. Replacement: Cells wear out. Every second, $2 \text{ million}$ red blood cells are destroyed and replaced by new ones formed in the bone marrow.
3. Repair: Injuries (cuts, fractures) are healed by cells dividing to cover gaps and join broken ends.
4. Reproduction: Unicellular organisms like Amoeba divide into two via mitosis. In higher forms, meiosis produces gametes (sperms and eggs).

The Cell Cycle

• Definition: A series of organized events leading to DNA duplication and subsequent division into two daughter cells. It follows the "divide, grow, and redivide" principle.
• Two Main Phases:     1. Interphase: The non-dividing phase.     2. M-phase (Mitosis): The dividing phase.

Interphase

• Formerly called the "resting phase," but it is actually very active in DNA synthesis.
• Stages of Interphase:     * First Growth Phase ($G_1$): RNA and proteins are synthesized; cytoplasm volume increases; mitochondria (animals) and chloroplasts (plants) divide. Cells may enter a resting phase ($R$/$G_0$) or proceed to synthesis.     * Synthesis Phase ($S$): More DNA is synthesized; chromosomes duplicate. DNA content doubles, but the chromosome number remains the same.     * Second Growth Phase ($G_2$): Shorter phase; continued synthesis of RNA and proteins necessary for division.

DNA Replication

• Occurs during the S-phase.
• The double helix opens at one end, and new strands form against the free strands.
• Each new DNA molecule contains one original strand and one new strand.

Life Span of Cells

• Brain/Nerve Cells: Most (cerebral cortex, eye lens) last a lifetime and are not replaced if they die.
• Skin Cells: Replaced roughly every $2$ weeks.
• Red Blood Cells: Last about $120$ days.
• Liver Cells: Replaced every $1$ to $2$ years.
• Bone Cells: Replaced every $10$ years in adults.
• Gut Lining (Epithelial): Last only $5$ days; other gut cells last $15$ years.
• Plant Growth: Meristems divide rapidly at growing points.
• Health Warning: Uncontrolled cell cycles can lead to tumors (cancerous or non-cancerous).
• Aging: In children, cell production exceeds cell death; in adults, it is equal; in the elderly, cell death exceeds production.

Mitosis: Phases and Characteristics

• Definition: Cell division where one parent cell produces two identical daughter cells with the same chromosome number.
• Steps: Highly categorized into Karyokinesis (nucleus division) and Cytokinesis (cytoplasm division).

Four Phases of Karyokinesis

1. Prophase (First Phase):     * Chromosomes become short, thick, and visible.     * Each chromosome appears as two sister chromatids joined at the centromere.     * Centrosome (in animal cells) splits; centrioles move to opposite poles.     * Aster rays radiate from centrioles.     * Spindle fibers (achromatic spindle) appear.     * Nuclear membrane and nucleolus disappear.
2. Metaphase (After Phase):     * Chromosomes align on the equatorial plane (equator).     * Each chromosome attaches to a spindle fiber by its centromere.
3. Anaphase (Up/Back Phase):     * Centromeres divide/split.     * Sister chromatids are pulled apart toward opposite poles by contracting spindle fibers.     * A furrow starts in the cell membrane (animal cells).
4. Telophase (End Phase):     * Chromatids reach poles and thin out to form chromatin threads.     * Nuclear membrane and nucleoli reappear.     * Spindle fibers disappear.

Cytokinesis

• Division of the cytoplasm following karyokinesis.
• In animal cells, a cleavage furrow deepens from the cell membrane toward the center until the cell splits.
• In plant cells, a cell plate is laid down at the center and grows outward (periphery) to divide the cell.

Differences in Mitosis: Animal vs. Plant Cells

Meiosis: Reduction Division

• Function: Production of sex cells or gametes (sperms/eggs in humans; pollen/ovules in plants).
• Location: Reproductive organs (testis and ovary; anthers and ovary).
• Chromosomal Change: Reductive division where the diploid number ($2n = 46$ in humans) is halved to the haploid number ($n = 23$).
• Restoration: When gametes fuse during fertilization, the diploid number ($2n$) is restored.
• Process: Consists of two divisions: Meiosis I (Reduction) and Meiosis II (Mitotic type).
• Note: The $G_2$ phase of the cell cycle is absent in meiosis; Prophase I is the most significant phase for variation.

Crossing Over and Variation

• Homologous Chromosomes: Pairs containing one paternal and one maternal chromosome.
• Synapsis: The pairing of homologous chromosomes.
• Crossing Over: The exchange of genetic material between non-sister chromatids of a homologous pair. This leads to genetic recombination.
• Chiasma: The X-shaped point of attachment between non-sister chromatids where crossing over occurs.
• Significance: Provides innumerable variations in progeny. This explains why siblings vary despite having the same parents.

Mitosis vs. Meiosis Summary

Questions & Discussion

• Progress Check Answers:     1. Chromatin fiber is made up of DNA and histones.     2. Two sister chromatids are attached at the centromere.     3. Structure of DNA was discovered by Watson and Crick.     4. Components of a nucleotide are phosphate, sugar, and nitrogenous base.     5. DNA wound around a histone octamer forms a nucleosome.     6. Sequence of nucleotides on a chromosome constitutes a gene.
• Terminology Note: The terms "parent" and "daughter" cells are conventional but technically limited because the parent cell ceases to exist as a separate entity upon division, and daughter cells are not necessarily feminine.
• Organelles: Mitochondria and chloroplasts have their own DNA and ribosomes; they divide by simple fission independent of nuclear division.