Human Biology Chapter 19: Cell Division

Chromosome Structure and Karyotyping

• Nucleus Role: The nucleus contains all genetic material required to direct the functions of the body.

• Chromosomes: These structures are composed of DNA and associated proteins.

  • Genes: The instructions within each chromosome are contained in genes, which in turn consist of DNA. Genes are the units of heredity that control traits, such as eye color and metabolism.

  • Chromatin: This is the collective term for DNA and the proteins that assist in its organizational structure. In a non-dividing cell, chromatin is typically a tangled mass of threads spread through the nucleus.

• Human Chromosome Count: Humans possess a total of $46$ chromosomes, organized into $23$ pairs.

  • Autosomes: There are $22$ pairs of autosomes, which are found in both males and females.

  • Sex Chromosomes: One pair of chromosomes determines gender. Females have two $X$ chromosomes ($XX$), while males have an $X$ and a $Y$ chromosome ($XY$).

  • SRY Gene: Located on the $Y$ chromosome, this gene triggers the development of testes.

• Karyotypes: A karyotype is a visual display of the chromosomes present within a cell.

  • Process: During cell division, chromatin condenses into visible chromosomes. Staining creates dark and light cross-bands. Computers help pair them based on size, shape, and banding patterns.

  • Sister Chromatids: In a dividing cell, each chromosome consists of two identical parts called sister chromatids, which contain the same genes.

  • Centromere: This region holds the sister chromatids together until they are separated during cell division. Once separated, they are called daughter chromosomes.

The Eukaryotic Cell Cycle and Interphase

• The Cell Cycle: This process consists of two primary parts: Interphase and Cell Division.

• Interphase: The vast majority of the cell cycle is spent in this phase. The cell carries out its normal functions and prepares for division.

  • Activities: The cell grows larger, doubles the number of organelles, and replicates its DNA (doubles the chromatin).

  • Stage $G_1$: The cell performs normal functions, doubles organelles, and accumulates materials for DNA synthesis.

  • Stage $S$ (Synthesis): DNA replication occurs. Following this stage, each chromosome consists of two identical sister chromatids.

  • Stage $G_2$: The cell synthesizes the proteins necessary for cell division.

  • Stage $G_0$: Some cells, like nerve and muscle cells, do not complete the cycle and are permanently arrested in $G_1$. This non-dividing state is called $G_0$.

• Cell Division: This follows interphase and consists of two stages:

  • Mitosis (M stage): Nuclear division; also called duplication division because the new nuclei have the same number and type of chromosomes ($2n = 46$) as the parent.

  • Cytokinesis: The division of the cytoplasm.

• Apoptosis: This is programmed cell death, which balances mitosis. It occurs when cells are no longer needed or are excessively damaged.

Control and Regulation of the Cell Cycle

• Checkpoints: These are delays in the cycle that ensure specific conditions are met before proceeding.

  • $G_1$ Checkpoint: The main checkpoint. If DNA is damaged, apoptosis occurs. If growth signals and nutrients are present, the cell is committed to divide. If not, it enters $G_0$.

  • $G_2$ Checkpoint: Verifies that DNA has replicated properly. If DNA is damaged and cannot be repaired, apoptosis occurs. It prevents the M stage from starting with un-replicated or damaged chromosomes.

  • Mitotic (M) Checkpoint: Occurs between metaphase and anaphase to ensure chromosomes are properly attached to the spindle fibers for accurate distribution.

• Regulatory Proteins: Proteins like $p53$ can stop the cycle at the $G_1$ checkpoint to repair DNA or trigger apoptosis.

• External Controls:

  • Signals: Hormones or growth factors bind to plasma membrane receptors.

  • Signal Transduction Pathway: A relay of proteins that passes the signal into the nucleus to activate genes.

  • Proto-oncogenes: Genes that stimulate the cell cycle.

  • Tumor Suppressor Genes: Genes that inhibit the cell cycle.

  • Cancer: Failure of these control mechanisms can lead to unrestricted cell growth.

Mitosis: Nuclear and Cytoplasmic Division

• Purpose: Mitosis is responsible for the development of embryos, fetuses, and children, as well as cell replacement in adults.

• Terminology: The dividing cell is the "parent cell," and the resulting identical cells are "daughter cells."

• The Mitotic Spindle:

  • Centrosome: The microtubule-organizing center. It duplicates and moves to opposite poles to form the spindle.

  • Centrioles: Short cylinders of microtubules within the centrosome.

  • Aster: An array of microtubules at the poles.

• Phases of Mitosis:

  1. Prophase: Centrosomes move apart; spindle fibers appear; nuclear envelope fragments; nucleolus disappears; chromosomes condense ($2$ sister chromatids visible).

  2. Prometaphase: Spindle fibers attach to centromeres; chromosomes are randomly placed.

  3. Metaphase: Chromosomes align at the metaphase plate (equidistant between poles).

  4. Anaphase: Centromeres divide; sister chromatids separate and move to opposite poles, now called daughter chromosomes.

  5. Telophase: Chromosomes arrive at poles and return to chromatin form; spindle disappears; nuclear envelopes and nucleoli reappear; results in two daughter nuclei.

• Cytokinesis: The cytoplasm divides via a cleavage furrow. Actin filaments form a contractile ring that pinches the cell in half.

Meiosis: Reduction Division and Genetic Variation

• Overview: Meiosis involves two consecutive divisions without an intervening interphase. It reduces the chromosome number from diploid ($2n$) to haploid ($n$).

• Outcome: Results in four genetically different daughter cells, each with one of each type of chromosome.

• Homologous Chromosomes: Pairs of chromosomes that look alike and carry genes for the same traits.

• Meiosis I:

  • Synapsis: Homologous chromosomes line up side-by-side during Prophase I.

  • Crossing-over: Exchange of genetic material between non-sister chromatids of a homologous pair during Prophase I, creating non-identical chromatids.

  • Metaphase I: Homologous pairs align independently at the equator (Independent Assortment).

  • Anaphase I: Homologous chromosomes separate (centromeres remain intact).

  • Telophase I: Daughter cells receive one chromosome from each homologous pair.

• Interkinesis: The period between Meiosis I and Meiosis II; DNA replication does not occur.

• Meiosis II:

  • The events are similar to mitosis (Prophase II, Metaphase II, Anaphase II, Telophase II), but the nuclei are haploid. At Anaphase II, centromeres divide and sister chromatids separate, becoming daughter chromosomes.

• Genetic Recombination: Ensures offspring are genetically diverse, which is essential for survival in changing conditions.

Spermatogenesis and Oogenesis: The Production of Gametes

• Spermatogenesis: Occurs in the testes and is continuous after puberty.

  • Production Rate: Approximately $300,000$ sperm per minute ($400 \text{ million}$ per day).

  • Process: Primary spermatocyte ($2n$) $\rightarrow$ Meiosis I $\rightarrow$ $2$ secondary spermatocytes ($n$) $\rightarrow$ Meiosis II $\rightarrow$ $4$ spermatids ($n$). All four daughter cells mature into sperm (spermatozoa).

• Oogenesis: Occurs in the ovaries.

  • Primary Oocytes: Arrested in Prophase I in immature follicles.

  • Meiosis I: Produces one secondary oocyte (receives most cytoplasm) and the first polar body (discards chromosomes).

  • Meiosis II: The secondary oocyte stops at Metaphase II. It only completes meiosis II if fertilized by a sperm.

  • Outcome: One functional egg and up to three polar bodies (which disintegrate).

  • Fertilization: Fusion of sperm and egg nuclei restores the diploid number ($2n$) in the zygote.

Comparative Analysis: Meiosis vs. Mitosis

• General Differences:

  • Meiosis requires two nuclear divisions; mitosis requires one.

  • Meiosis produces four daughter cells; mitosis produces two.

  • Meiosis produces haploid ($n$) cells; mitosis produces diploid ($2n$) cells.

  • Meiosis daughter cells are genetically unique; mitosis daughter cells are identical.

• Occurrence: Meiosis occurs only in reproductive organs (gamete production); mitosis occurs in all tissues for growth and repair.

• Process Comparison (Meiosis I vs. Mitosis):

  • Prophase: Pairing and crossing-over occur in Meiosis I but not in Mitosis.

  • Metaphase: Homologous pairs align in Meiosis I; individual chromosomes align in Mitosis.

  • Anaphase: Homologous chromosomes separate in Meiosis I (centromeres intact); sister chromatids separate in Mitosis.

• Process Comparison (Meiosis II vs. Mitosis): The events are identical except that Meiosis II involves a haploid number of chromosomes.

Chromosome Inheritance: Numerical Abnormalities

• Nondisjunction: The failure of chromosomes to separate correctly during Meiosis I or II.

• Trisomy: One chromosome type is present in three copies ($2n + 1$).

• Monosomy: One chromosome type is present in a single copy ($2n - 1$).

• Survival Factors:

  • Autosomal monosomy is fatal.

  • Most autosomal trisomies are fatal; Trisomy $21$ is a notable exception.

  • Sex chromosome abnormalities are better tolerated due to the formation of Barr bodies (inactive $X$ chromosomes).

• Down Syndrome (Trisomy 21): The most common autosomal trisomy.

  • Characteristics: Short stature, eyelid fold, flat facial profile, stubby fingers, wide gap between first and second toes, large fissured tongue, round head, and single transverse palmar crease (STPC).

  • Cognition: Varies from developmental delays to intellectual disability. Risk increases for mothers over the age of $40$.

  • Gart Gene: Present on Chromosome $21$.

Sex Chromosomal Syndromes

• Turner Syndrome ($XO$): Females with only one $X$ chromosome.

  • Features: Short stature, broad chest, webbed neck. Ovaries/uterus are underdeveloped (no puberty or menstruation). No intellectual disability.

• Klinefelter Syndrome ($47, XXY$): Males with two $X$ and one $Y$ chromosome.

  • Features: Underdeveloped testes/prostate, lack of facial hair, possible breast development, large hands/feet, long limbs. Sterility. Slow to learn but no inherent intellectual disability.

  • Health: Increased risk of breast cancer, osteoporosis, and lupus.

• Poly-X Syndrome: Females with more than two $X$ chromosomes. Usually tall and thin; may have delayed motor/language development but children typically have normal karyotypes.

• Jacobs Syndrome ($XYY$): Males resulting from nondisjunction during spermatogenesis. Typically taller than average, persistent acne, and speech/reading problems; fertile.

Structural Abnormalities in Chromosomes

• Environmental Causes: Radiation, viruses, and organic chemicals can cause breaks in chromosomes.

• Types of Mutations:

  • Deletion: A segment of a chromosome breaks off.

    • Williams syndrome: Deletion of an end piece of Chromosome $7$ (elastin gene missing); features include friendly temperament, cardiovascular issues, and premature skin aging.

    • Cri du chat syndrome: Deletion of an end piece of Chromosome $5$; causes small head, intellectual disability, and a cat-like cry due to larynx/glottis defects.

  • Duplication: A chromosomal segment is repeated within the same chromosome.

  • Inversion: A segment is turned $180$ degrees. Usually asymptomatic as all genes are present, but can cause duplication/deletion issues during crossing-over.

  • Translocation: Movement of a segment between nonhomologous chromosomes.

    • Alagille syndrome: Translocation between Chromosomes $2$ and $20$; features heart defects (tetralogy of Fallot) and clubbing of fingers.

    • Down Syndrome: In $5\%$ of cases, it is caused by a translocation between Chromosomes $21$ and $14$.