BIO unit 4: Cell Reproduction, Mitosis, and Meiosis

Cell Reproduction and Mitosis

Importance of Cell Division

  • Cell division is essential for the following: 1) Growth and Development

    • Responsible for the increase in the number of cells in an organism.

    • Continuous cell division leads from an embryo to an adult.

    • Involves processes:

      • Dedifferentiation

        • Refers to the increase in the number of stem cells.

      • Differentiation

        • Unspecialized cells are transformed into specialized cell types.

          2) Tissue Repair

    • Essential for repairing damaged tissues in an organism.

    • Necessary to replace cells that quickly wear out, e.g.:

      • Red Blood Cells

        • Among the shortest-lived cells in the human body.

          3) Replacement of Old Cells

    • Many cell types have a limited lifespan and therefore require division for replacement.

    • Example: Skin cells constantly shed and are replaced by new ones.

Asexual Reproduction

  • Binary Fission

    • Common method of asexual reproduction in single-celled organisms (e.g., bacteria).

    • Process involves the division of a parent cell into two identical daughter cells.

Steps in Binary Fission

1) DNA Replication

  • Duplication of genetic material occurs.

    2) Cell Growth

  • The cell enlarges in preparation for division.

    3) Segregation

  • Two sets of DNA move to opposite ends of the cell.

    4) Division

  • Cell membrane pinches in, creating two new cells, each with a complete set of DNA.

    • Analogy: Tying a plastic bag full of water with a string in the middle to visualize cellular division.

    • FtsZ Protein: Forms a ring-like structure at the cell's midpoint, aiding in cell division.

The Cell Cycle

  • The cell cycle is a series of stages for cells to grow and divide accurately.

  • Importance of Cell Cycle: Ensures new cells have the correct DNA amount.

  • Duration of Cell Cycle: Varies significantly across organisms and cell types.

    • Example: Bean plant cells take approximately 19 hours; animal embryo cells can divide in under 20 minutes; some human cells (skin and bone) average about 16 hours.

Phases of the Cell Cycle

1) Interphase

  • Subdivided into three phases:

  • G1 (Gap 1):

  • Cell grows, performs normal functions, and accumulates energy and resources for DNA replication.

  • S (Synthesis):

  • DNA replication occurs; genetic material is duplicated.

  • G2 (Gap 2):

  • The cell continues growth and prepares for division; it checks replicated DNA for errors.

2) Mitotic (M) Phase

  • Consists of five sub-phases:

    • Prophase: Chromatin condenses into visible chromosomes; nuclear envelope begins to break down; mitotic spindle forms.

    • Metaphase: Condensed chromosomes align at the metaphase plate (equator of the cell).

    • Anaphase: Sister chromatids (identical halves of a duplicated chromosome) are separated and moved towards opposite poles of the cell.

    • Telophase: Separated chromatids arrive at the poles, and the nuclear envelope reforms.

    • Cytokinesis: The cytoplasm divides, resulting in two separate daughter cells.

Results of Mitosis

  • Mitosis yields two genetically identical daughter cells with the same chromosome number as the parent cell.

  • Key outcomes include:

    1) Chromosome Number: Daughter cells maintain the diploid chromosome number of the parent cell.

    2) Genetic Identity: Each daughter cell retains identical DNA and genetic information to the parent.

    3) Cell Size: Daughter cells are usually similar in size to the parent cell.

Types of Asexual Reproduction

1) Binary Fission: Parent cell splits into two nearly equal offspring.

2) Fragmentation: Body divides into pieces, leading to the formation of new organisms (e.g., stars, fungi).

3) Budding: Outgrowth forms on the parent organism, developing into a new individual (e.g., yeast).

4) Vegetative Propagation: Asexual reproduction in plants occurs via vegetative parts (roots, stems).

Control of the Cell Cycle

  • G0 Phase: Cells in a resting state that temporarily exit the active cell cycle and do not divide.

  • Cells can enter the G0 phase due to:

    1) Differentiation: Specialized cells may remain in G0 indefinitely.

    2) Senescence: Aging or damaged cells may cease dividing to avoid mutations.

    3) Lack of Stimuli: Cells require external signals to re-enter the cycle.

    4) Tissue Repair: Cells can reactivate to repair tissue after injury.

White Blood Cells

  • Function: Immune response against infections.

  • Generally remain in G0 until an infection triggers their re-entry into the cell cycle.

Length of the Cell Cycle

  • Highly variable depending on cell type.

  • For example, in human cells with a 24-hour cycle:

    • G1 lasts ~9 hours.

    • S lasts ~10 hours.

    • G2 lasts ~4.5 hours.

    • M lasts ~0.5 hours.

  • Control mechanisms regulate the timing of the events in the cycle.

Regulation of the Cell Cycle by External Events

  • Events that trigger or inhibit cell division include hormonal signals:

    • Human Growth Hormone (HGH): Lack leads to dwarfism; excess can cause gigantism.

    • Sex Hormones: Estrogen, progesterone, testosterone regulate reproductive tissues.

    • Thyroid Hormones and Cortisol: Affect regulation during stress.

    • Crowding: Inhibits cell division.

Regulation of Internal Checkpoints

  • Cell cycle checkpoints prevent mutations during chromosomal duplication and ensure orderly progression.

    • These are important moments in which a cell decides whether it will continue with the cell cycle or not.

  • Importance of these checkpoints:

    1) It maintains genomic stability.

    2) It prevents the proliferation of cells with DNA damage or other abnormalities, which could lead to diseases such as cancer.

  • These three checkpoints are regulated by various proteins, including Cyclins and cyclin-dependent kinases (CDKs).

  • The activity of these proteins results in opening or closing the checkpoints.

  • If a cell fails to pass a checkpoint, it can result in cell cycle arrest, to eliminate the damaged cell. This strict checkpoint regulation prevents the spread of cells with DNA damage, maintaining genetic integrity and overall health.

Checkpoints in the Cell Cycle

  • There are three major checkpoints:

    1) G1/S Checkpoint

    • The checkpoint of the G1 phase is located at the transition between G1 and S phase.

    • At this point, the cell decides if it is ready to start the process of DNA duplication (S phase).

    • This is a critical checkpoint because once the cell has passed, it is committed to division; there is no way back.

    • This checkpoint checks for:

      • Cell size

      • Nutrients

      • Growth factors

      • DNA damage

    • It is the point where the cell “decides” whether it will proceed with the cell cycle and divide or enter a non-dividing state called G0.

    • It checks whether the cell is big enough and has made the proper proteins for the synthesis phase. Also, checking for nutrients, growth factors, and DNA damage is performed in this stage.

    • At this checkpoint, the cell evaluates external signals and checks for DNA damage. If the conditions are favorable and there is no DNA damage, the cell will continue into the S phase to begin DNA replication. If the cell does not meet all requirements, it is not allowed to progress into the S phase.

    • Note: The cell can stop the cycle and attempt to fix the problematic condition, or the cell can advance into G0 and await further signals when conditions improve.

    • What is checked at G1: The questions that need to be addressed in G1 inspection:

      • Cell size: Is the cell large enough to contain the two sets of DNA in S phase? (Growth further occurs during G2 phase and is checked again there)

      • Nutrients: Are there enough nutrients to provide energy for the cell?

      • Building blocks: Are there enough building blocks (nucleotides) to make DNA in S phase?

      • DNA integrity: Is the DNA undamaged and, therefore, suitable for copying in S phase?

    • Once all the boxes are checked, the cell is ready.

    2) G2/S Checkpoint

    • Occurs at the end of G2 phase.

    • Ensures that DNA replication in the S phase has been completed accurately and that there are no errors or DNA damage.

    • If DNA damage is detected, the cell may pause in G2 to allow for repair. If repair is not possible, the cell may undergo apoptosis (cell death).

    • Checks for:

      • DNA damage

      • DNA replication completeness

    3) M Checkpoint (spindle checkpoint)

    • Occurs at the metaphase stage of mitosis (M phase).

    • Ensures that all the chromosomes are correctly attached to the spindle before the cell proceeds to anaphase.

    • This checkpoint prevents the separation of sister chromatids until they are properly aligned on the metaphase plate.

    • Checks for:

      • Chromosome attachment to spindle at metaphase plate

Regulator molecules of the cell cycle

  • There are two groups of intercellular molecules (protein) that regulate the cell cycle.

  • These regulatory molecules either promote progress of the cell to the next phase (positive regulation) or stop the cycle (negative regulation).

Positive regulation of the cell cycle

  • Two groups of proteins, called cyclins and cyclin-dependent kinases (CDKs), are responsible for the progress of the cell through the various checkpoints.

Cyclin-dependent kinase (CDKs)

  • CDKs are enzymes (kinases) that phosphorylate proteins (cyclin).

  • Cyclins regulate the cell cycle only when they are tightly bound to CDKs.

Negative regulation of the cell cycle

  • The second group of cell cycle regulatory molecules are negative regulators.

  • Negative regulators stop or pause the cell cycle. Remember that in positive regulation, active molecules cause the cycle to progress.

  • The best understood negative regulator molecules are retinoblastoma protein (Rb).

    • Rb proteins are a group of tumor-suppressor proteins common in many cells.

    • The negative regulation of the cell cycle by Rb is a critical mechanism that helps to control and prevent uncontrolled cell division and tumorigenesis.

Summary of Cell Cycle Checkpoints

  • Each step of the cell cycle is monitored by internal controls called checkpoints.

  • There are three major checkpoints in the cell cycle:

    1) One near the end of G1

    2) Second at the G2/M transition

    3) Third during metaphase

  • Positive regulator molecules allow the cell cycle to advance to the next stage.

  • Negative regulators check cell conditions and can stop the cycle until requirements are met.

Biology of Cancer

  • Sir William Richard Shaboe Doll: Researcher

Cancer Statistics

  • Men vs Women

    • Men: 29% - 11% - 9% - …

    • Women: 26% - …

  • In 2024, it is estimated that around 611,720 people in the US will die from cancer.

    • This number corresponds to approximately 1676 deaths per day on average.

  • In 2025, an estimated 1694 deaths per day.

Most Diagnosed Cancers in the US in 2024

  • Women

    • Breast cancer

    • Lung cancer

    • Colorectal cancer

    • Uterine cancer

    • Ovarian cancer

  • Men

    • Prostate cancer

    • Lung cancer

    • Colorectal cancer

    • Bladder cancer

    • Melanoma of the skin

Normal Cell Division

  • In normal cells, division is controlled.

  • Normal cells divide only when appropriate for their type and circumstances: "A normal cell divides only when it needs to."

  • Normal cells do not lose their specialized differentiated identity.

  • The generation of new cells replaces old or damaged cells.

Example: Skin Cells

  • The outer layer of skin (epidermis) is about 12 cells thick.

  • Cells in the basal layer (bottom row) divide just fast enough to replenish cells that are shed.

  • When a basal cell divides, it produces two cells:

    • One remains in the basal layer and retains the capacity to divide.

    • The other migrates out of the basal layer and loses the capacity to divide.

Abnormal Cell Division (Cancer Cell Initiation)

  • Cancer cells are initiated when they lose their ability to be controlled within the cell cycle.

  • Skin cancer begins when the normal balance between cell division and cell loss is disrupted.

    • Basal cells divide faster than needed to replenish the cells being shed.

    • With each division, both newly formed cells will often retain the capacity to divide, leading to an increased number of dividing cells.

  • This creates a growing mass of tissue called a "tumor" or "neoplasm."

  • As more and more dividing cells accumulate, the normal organization of the tissue gradually becomes disrupted.

Tumors (Neoplasms)

  • Are masses of cells that are no longer under control of division (Ex: warts).

Cell Differentiation

  • Stem cells

    • An unspecialized cell that can divide without limit as needed.

    • Can, under specific conditions, differentiate into specialized cells.

  • Cell differentiation

    • The process where a cell changes from one type to many different types.

    • Involves differences in morphological structure and physiological function.

  • All organisms begin from a single cell.

Regulation of Cell Differentiation

  • Involves the activation or inactivation of certain genes.

  • Identical cells develop into different types of cells because of genes.

  • There are many genes in a cell, and when one is activated, it turns into a specialized cell (e.g., muscle cells, nerve cells).

Gene Activation Factors

Cells activate specific genes based on two factors:

  1. Their interactions with nearby (neighboring) cells (Cell-cell interaction).

  2. The surrounding environment (extracellular matrix or ECM) (Cell-matrix interaction).

    • ECM provides structural support and plays a critical role in regulating cell differentiation.

    • It is a network of proteins, sugars, and other molecules found outside of cells of tissue.

    • This process helps dedifferentiated cells become differentiated.

Normal vs. Cancerous Cells in Tissues

  • In healthy tissues

    • Cells interact well with each other and the ECM to maintain tissue integrity and function.

  • In cancerous cells (tumor)

    • These interactions can be disrupted, leading to uncontrolled growth and changes in how the cells behave.

  • Note: Loss of responsiveness to the extracellular matrix (ECM) and neighboring cells can lead to key characteristics of tumors.

Cell-Cell Communication

  • Cells within tissues communicate with each other through various signaling pathways.

  • This communication is essential for coordinating the process of cell differentiation.

  • In the context of cancer and tumor formation, several mechanisms can lead to the loss of the ability of cells to sense the ECM and neighboring cells.

    • Sometimes the ability of cells to sense the ECM and neighboring cells is lost, therefore cancer and tumor cells are developed.

Types of Signaling

  • Autocrine signaling: A cell targets itself.

  • Paracrine signaling: A cell signals a nearby cell.

  • Endocrine signaling: A cell targets a distant cell through the bloodstream.

  • Direct signaling: A cell targets a neighboring cell through a gap junction.

Factors That Cause These Disorders (leading to Cancer)

  • Genetic mutations

    • Tumor cells often accumulate genetic mutations that disrupt the normal signaling pathways responsible for ECM and cell-cell communication.

    • These mutations can lead to uncontrolled cell growth and reduced responsiveness to regulatory signals.

  • Altered Cell-ECM interactions

    • Tumor cells may exhibit changes in their interactions with the ECM, which can promote uncontrolled cell division.

  • Loss of contact inhibition

    • Normal cells exhibit a phenomenon called "contact inhibition," using this strategy to stop dividing when they meet neighboring cells.

    • Tumor cells often lose this inhibition, allowing them to grow uncontrollably even near other cells.

  • The loss of responsiveness to the ECM and neighboring cells is a critical aspect of tumor development and progression.

How Cancer Spreads

  • Local invasion: Spreading cancer by local invasion (worse).

  • Metastasis: Travel via blood, lymph to establish colonies in distant tissues.

Evolution of a Cancer

  • Hyperplasia: An increase in the number of cells in a tissue, leading to tissue enlargement. It's often benign but can sometimes lead to cancer.

  • Dysplasia: Abnormal changes in the size, shape, and organization of cells, indicating potential precancerous changes.

  • In situ cancer: Cancerous cells that stay in the place where they started and have not spread to nearby tissues. This is an early stage of cancer.

  • Invasive cancer: Cancer cells that have spread beyond their original site and invaded nearby tissues, indicating a more serious progression that may spread to other body parts.

How Cancers Harm or Kill Us

  • Use nutrients, but do not contribute to function.

  • Expand, causing pressure on other organs, distorting them, or interfering with their blood, lymphatic, or nervous access.

  • Invade and weaken bone.

  • Produce chemicals that disrupt function (anorexia, inflammation, coagulation, pain, blood pressure).

Sexual Reproduction and Meiosis

Sexual Reproduction

  • Sexual reproduction is another way that a new organism can be produced.

  • During sexual reproduction, two sex cells, sometimes called an egg and a sperm, come together.

    • Male sperm + female sperm (egg cell) = zygote
      ightarrow embryo
      ightarrow baby.

  • Sex cells are formed from cells in reproductive organs.

  • The joining of an egg and a sperm is called fertilization, and the cell that forms is called a zygote.

  • Note: In sexual reproduction, because the egg and the sperm come from two different organisms (in genetic information) of the same species, following fertilization and cell division, a new organism with a unique identity develops.

Diploid Cells and Haploid Cells

  • The number of body cells is much more than sex cells.

  • Your brain, skin, bones, and other tissues and organs are formed from body cells (they are diploid cells).

  • A typical human body cell has 46 chromosomes.

  • The number of total chromosomes in the non-gamete cells of a particular species is called the diploid number for that species.

    • This diploid number of humans is 46, and the diploid number of nematodes is 4.

  • There are two ways cell division can happen in animals and plants, called mitosis and meiosis.

    • When a cell divides by way of mitosis:

      • Generating two clones of itself, each with the same number of chromosomes.

    • When a cell divides by way of meiosis:

      • Producing four cells, called gametes (sperm in males and eggs in females).

    • Note: Unlike in mitosis, the gametes produced by meiosis are not clones of the original cell, because each gamete has exactly half as many chromosomes as the original cell.

The Concept of a Chromosome

  • Before discovering chromosomes, scientists observed genetic material as threads or loops, known as chromatin.

  • Chromatin is made up of a twisted mass of strands.

  • Chromatin is made up of a tangled mass of strands and is visible only when the cell is not dividing.

  • A chromatin is a long strand of DNA with histone proteins attached like beads on a string.

  • Sister chromatids: Identical copies of a chromosome that are created during DNA replication.

  • Homologous chromosomes: Two different chromosomes in a pair that have the same genes but may have different alleles.

Meiosis Stages

  • Meiosis is divided into main stages: Meiosis 1 and Meiosis 2, and both occur after interphase.

1) Interphase (preparation for meiosis)

- **G1 phase**: The cell grows and carries out normal functions.

- **S phase**: DNA is replicated, resulting in two identical copies of each chromosome.

- **G2 phase**: Further growth and preparation for cell division.

2) Meiosis 1 (reduction division)

- **Prophase 1**
    - Chromosomes condense.
    - Homologous chromosomes pair up, and crossing over occurs.

- **Metaphase 1**: Homologous chromosome pairs align at the cell’s equator.

- **Anaphase 1**: Homologous chromosomes are pulled to opposite poles of the cell.

- **Telophase 1**: Chromosomes reach the poles, and the cell divides into two daughter cells.

3) Meiosis 2 (division of haploid cells)

- **Prophase 2**: Chromosomes re-condense in the two haploid cells.

- **Metaphase 2**: Chromosomes align at the equator of each haploid cell.

- **Anaphase 2**: Sister chromatids are separated and pulled to opposite poles.

- **Telophase 2**: Chromatids reach the poles, and the two cells divide, resulting in four haploid daughter cells.

What happens during Prophase 1 of Meiosis 1

1) Chromosome condensation: The chromatin condenses into visible chromosomes, each consisting of two sister chromatids.

2) Homologous chromosome pairing: Homologous chromosomes come together to form pairs in a process called synapsis. Each pair consists of four chromatids.

3) Crossing over: In the paired chromosomes, segments of chromatids may be exchanged between homologous chromosomes.

4) Formation of the spindle apparatus from the centrioles.

5) Nuclear envelope breakdown.

6) Chromosomes attach to spindle fibers.

Metaphase 1 of Meiosis

  • Tetrads align at the cell’s equator (the metaphase plate).

Anaphase 1 of Meiosis

  • Homologous chromosomes are pulled apart and move to opposite poles of the cell.

  • The chromosome number is halved as each daughter cell receives one set of chromosomes.

Telophase 1 of Meiosis

  • Nuclear envelopes may reform.

  • The cell divides into two daughter cells, each with a haploid number of chromosomes.

Meiosis 2

  • Each of the two haploid daughter cells from Meiosis 1 undergo a second division, forming four haploid gametes.

  • Meiosis 2 consists of the following phases:

1) Prophase 2

- Chromosomes condense.

- A new spindle apparatus forms in each of the two haploid daughter cells.

2) Metaphase 2

- Chromosomes align at the metaphase plate in each of the two haploid daughter cells.

3) Anaphase 2

- Sister chromatids are separated and move to opposite poles of each haploid daughter cell.

4) Telophase 2 and Cytokinesis

- Nuclear envelope reforms.

- The two haploid daughter cells from Meiosis 1 each divide into two, resulting in a total of four haploid gametes.

What is the final result of Meiosis?

  • Thus, at the end of Meiosis 2, four non-identical, haploid daughter cells are formed, each having half the chromosome number as the original parent cell.

Main Differences between Meiosis 1 and Meiosis 2

  • In Meiosis 1, a pair of homologous chromosomes separate to produce two diploid daughter cells, each having half the number of chromosomes as the parent cell.

  • In contrast, during Meiosis 2, sister chromatids separate to produce four haploid daughter cells. Also, unlike Meiosis 1, no genetic recombination by crossing over occurs in Meiosis 2.

Purpose of Meiosis

  • Maintaining chromosome number in organisms

    • To maintain chromosome number, gametes formed by meiosis must have half the chromosomes (23) of the parent cell.

    • When the sex cells fuse to form a zygote, the usual chromosome number of 46 chromosomes is restored in the new individual.

    • If the chromosomal reduction process is not maintained, it could cause genetic abnormality in the child.

    • Down syndrome is a genetic disorder caused by the presence of an extra copy of chromosome 21. Children with Down syndrome often experience:
      1) Developmental delays.
      2) Intellectual disabilities.
      3) Distinct facial features.
      4) Various health issues such as heart defects and low muscle tone.

  • Create genetic diversity

    • The exchange of genetic information between the pair of homologous chromosomes allows genetic variation among the population.

    • These variations form the basis of the evolutionary process.

  • Repairs genetic defects

    • Recombination in meiosis helps repair genetic abnormalities in individuals.

    • Recombination in meiosis can replace a genetic defect from a parent, allowing a healthy individual to form.

What would happen if the number of chromosomes were not halved during meiosis before fertilization?

  • Polyploid cells with multiple sets of chromosomes would result.

  • Polyploid cells have more than two complete sets chromosomes, unlike the normal diploid state with two sets.

  • Note: Although plants with polyploid cells are often produced, most animals do not survive with a polyploid cell.

The Necessity of Meiosis in Sexual Reproduction

1) Reduction of chromosome number.

2) Genetic diversity.

3) Adaptation and evolution: The genetic diversity generated by meiosis is essential for adaptation and evolution.

Cell Reproduction and Mitosis

Importance of Cell Division

  • Cell division is essential for the following: 1) Growth and Development

    • Responsible for the increase in the number of cells in an organism.

    • Continuous cell division leads from an embryo to an adult.

    • Involves processes:

      • Dedifferentiation

        • Refers to the increase in the number of stem cells.

      • Differentiation

        • Unspecialized cells are transformed into specialized cell types.

          2) Tissue Repair

    • Essential for repairing damaged tissues in an organism.

    • Necessary to replace cells that quickly wear out, e.g.:

      • Red Blood Cells

        • Among the shortest-lived cells in the human body.

          3) Replacement of Old Cells

    • Many cell types have a limited lifespan and therefore require division for replacement.

    • Example: Skin cells constantly shed and are replaced by new ones.

Asexual Reproduction

  • Binary Fission

    • Common method of asexual reproduction in single-celled organisms (e.g., bacteria).

    • Process involves the division of a parent cell into two identical daughter cells.

Steps in Binary Fission

1) DNA Replication

  • Duplication of genetic material occurs.

    2) Cell Growth

  • The cell enlarges in preparation for division.

    3) Segregation

  • Two sets of DNA move to opposite ends of the cell.

    4) Division

  • Cell membrane pinches in, creating two new cells, each with a complete set of DNA.

    • Analogy: Tying a plastic bag full of water with a string in the middle to visualize cellular division.

    • FtsZ Protein: Forms a ring-like structure at the cell's midpoint, aiding in cell division.

The Cell Cycle

  • The cell cycle is a series of stages for cells to grow and divide accurately.

  • Importance of Cell Cycle: Ensures new cells have the correct DNA amount.

  • Duration of Cell Cycle: Varies significantly across organisms and cell types.

    • Example: Bean plant cells take approximately 19 hours; animal embryo cells can divide in under 20 minutes; some human cells (skin and bone) average about 16 hours.

Phases of the Cell Cycle

1) Interphase

  • Subdivided into three phases:

  • G1 (Gap 1):

  • Cell grows, performs normal functions, and accumulates energy and resources for DNA replication.

  • S (Synthesis):

  • DNA replication occurs; genetic material is duplicated.

  • G2 (Gap 2):

  • The cell continues growth and prepares for division; it checks replicated DNA for errors.

2) Mitotic (M) Phase

  • Consists of five sub-phases:

    • Prophase: Chromatin condenses into visible chromosomes; nuclear envelope begins to break down; mitotic spindle forms.

    • Metaphase: Condensed chromosomes align at the metaphase plate (equator of the cell).

    • Anaphase: Sister chromatids (identical halves of a duplicated chromosome) are separated and moved towards opposite poles of the cell.

    • Telophase: Separated chromatids arrive at the poles, and the nuclear envelope reforms.

    • Cytokinesis: The cytoplasm divides, resulting in two separate daughter cells.

Results of Mitosis

  • Mitosis yields two genetically identical daughter cells with the same chromosome number as the parent cell.

  • Key outcomes include:

    1) Chromosome Number: Daughter cells maintain the diploid chromosome number of the parent cell.

    2) Genetic Identity: Each daughter cell retains identical DNA and genetic information to the parent.

    3) Cell Size: Daughter cells are usually similar in size to the parent cell.

Types of Asexual Reproduction

1) Binary Fission: Parent cell splits into two nearly equal offspring.

2) Fragmentation: Body divides into pieces, leading to the formation of new organisms (e.g., stars, fungi).

3) Budding: Outgrowth forms on the parent organism, developing into a new individual (e.g., yeast).

4) Vegetative Propagation: Asexual reproduction in plants occurs via vegetative parts (roots, stems).

Control of the Cell Cycle

  • G0 Phase: Cells in a resting state that temporarily exit the active cell cycle and do not divide.

  • Cells can enter the G0 phase due to:

    1) Differentiation: Specialized cells may remain in G0 indefinitely.

    2) Senescence: Aging or damaged cells may cease dividing to avoid mutations.

    3) Lack of Stimuli: Cells require external signals to re-enter the cycle.

    4) Tissue Repair: Cells can reactivate to repair tissue after injury.

White Blood Cells

  • Function: Immune response against infections.

  • Generally remain in G0 until an infection triggers their re-entry into the cell cycle.

Length of the Cell Cycle

  • Highly variable depending on cell type.

  • For example, in human cells with a 24-hour cycle:

    • G1 lasts ~9 hours.

    • S lasts ~10 hours.

    • G2 lasts ~4.5 hours.

    • M lasts ~0.5 hours.

  • Control mechanisms regulate the timing of the events in the cycle.

Regulation of the Cell Cycle by External Events

  • Events that trigger or inhibit cell division include hormonal signals:

    • Human Growth Hormone (HGH): Lack leads to dwarfism; excess can cause gigantism.

    • Sex Hormones: Estrogen, progesterone, testosterone regulate reproductive tissues.

    • Thyroid Hormones and Cortisol: Affect regulation during stress.

    • Crowding: Inhibits cell division.

Regulation of Internal Checkpoints

  • Cell cycle checkpoints prevent mutations during chromosomal duplication and ensure orderly progression.

    • These are important moments in which a cell decides whether it will continue with the cell cycle or not.

  • Importance of these checkpoints:

    1) It maintains genomic stability.

    2) It prevents the proliferation of cells with DNA damage or other abnormalities, which could lead to diseases such as cancer.

  • These three checkpoints are regulated by various proteins, including Cyclins and cyclin-dependent kinases (CDKs).

  • The activity of these proteins results in opening or closing the checkpoints.

  • If a cell fails to pass a checkpoint, it can result in cell cycle arrest, to eliminate the damaged cell. This strict checkpoint regulation prevents the spread of cells with DNA damage, maintaining genetic integrity and overall health.

Checkpoints in the Cell Cycle

  • There are three major checkpoints:

    1) G1/S Checkpoint

    • The checkpoint of the G1 phase is located at the transition between G1 and S phase.

    • At this point, the cell decides if it is ready to start the process of DNA duplication (S phase).

    • This is a critical checkpoint because once the cell has passed, it is committed to division; there is no way back.

    • This checkpoint checks for:

      • Cell size

      • Nutrients

      • Growth factors

      • DNA damage

    • It is the point where the cell “decides” whether it will proceed with the cell cycle and divide or enter a non-dividing state called G0.

    • It checks whether the cell is big enough and has made the proper proteins for the synthesis phase. Also, checking for nutrients, growth factors, and DNA damage is performed in this stage.

    • At this checkpoint, the cell evaluates external signals and checks for DNA damage. If the conditions are favorable and there is no DNA damage, the cell will continue into the S phase to begin DNA replication. If the cell does not meet all requirements, it is not allowed to progress into the S phase.

    • Note: The cell can stop the cycle and attempt to fix the problematic condition, or the cell can advance into G0 and await further signals when conditions improve.

    • What is checked at G1: The questions that need to be addressed in G1 inspection:

      • Cell size: Is the cell large enough to contain the two sets of DNA in S phase? (Growth further occurs during G2 phase and is checked again there)

      • Nutrients: Are there enough nutrients to provide energy for the cell?

      • Building blocks: Are there enough building blocks (nucleotides) to make DNA in S phase?

      • DNA integrity: Is the DNA undamaged and, therefore, suitable for copying in S phase?

    • Once all the boxes are checked, the cell is ready.

    2) G2/S Checkpoint

    • Occurs at the end of G2 phase.

    • Ensures that DNA replication in the S phase has been completed accurately and that there are no errors or DNA damage.

    • If DNA damage is detected, the cell may pause in G2 to allow for repair. If repair is not possible, the cell may undergo apoptosis (cell death).

    • Checks for:

      • DNA damage

      • DNA replication completeness

    3) M Checkpoint (spindle checkpoint)

    • Occurs at the metaphase stage of mitosis (M phase).

    • Ensures that all the chromosomes are correctly attached to the spindle before the cell proceeds to anaphase.

    • This checkpoint prevents the separation of sister chromatids until they are properly aligned on the metaphase plate.

    • Checks for:

      • Chromosome attachment to spindle at metaphase plate

Regulator molecules of the cell cycle

  • There are two groups of intercellular molecules (protein) that regulate the cell cycle.

  • These regulatory molecules either promote progress of the cell to the next phase (positive regulation) or stop the cycle (negative regulation).

Positive regulation of the cell cycle

  • Two groups of proteins, called cyclins and cyclin-dependent kinases (CDKs), are responsible for the progress of the cell through the various checkpoints.

Cyclin-dependent kinase (CDKs)

  • CDKs are enzymes (kinases) that phosphorylate proteins (cyclin).

  • Cyclins regulate the cell cycle only when they are tightly bound to CDKs.

Negative regulation of the cell cycle

  • The second group of cell cycle regulatory molecules are negative regulators.

  • Negative regulators stop or pause the cell cycle. Remember that in positive regulation, active molecules cause the cycle to progress.

  • The best understood negative regulator molecules are retinoblastoma protein (Rb).

    • Rb proteins are a group of tumor-suppressor proteins common in many cells.

    • The negative regulation of the cell cycle by Rb is a critical mechanism that helps to control and prevent uncontrolled cell division and tumorigenesis.

Summary of Cell Cycle Checkpoints

  • Each step of the cell cycle is monitored by internal controls called checkpoints.

  • There are three major checkpoints in the cell cycle:

    1) One near the end of G1

    2) Second at the G2/M transition

    3) Third during metaphase

  • Positive regulator molecules allow the cell cycle to advance to the next stage.

  • Negative regulators check cell conditions and can stop the cycle until requirements are met.

Biology of Cancer

  • Sir William Richard Shaboe Doll: Researcher

Cancer Statistics

  • Men vs Women

    • Men: 29% - 11% - 9% - …

    • Women: 26% - …

  • In 2024, it is estimated that around 611,720 people in the US will die from cancer.

    • This number corresponds to approximately 1676 deaths per day on average.

  • In 2025, an estimated 1694 deaths per day.

Most Diagnosed Cancers in the US in 2024

  • Women

    • Breast cancer

    • Lung cancer

    • Colorectal cancer

    • Uterine cancer

    • Ovarian cancer

  • Men

    • Prostate cancer

    • Lung cancer

    • Colorectal cancer

    • Bladder cancer

    • Melanoma of the skin

Normal Cell Division

  • In normal cells, division is controlled.

  • Normal cells divide only when appropriate for their type and circumstances: "A normal cell divides only when it needs to."

  • Normal cells do not lose their specialized differentiated identity.

  • The generation of new cells replaces old or damaged cells.

Example: Skin Cells

  • The outer layer of skin (epidermis) is about 12 cells thick.

  • Cells in the basal layer (bottom row) divide just fast enough to replenish cells that are shed.

  • When a basal cell divides, it produces two cells:

    • One remains in the basal layer and retains the capacity to divide.

    • The other migrates out of the basal layer and loses the capacity to divide.

Abnormal Cell Division (Cancer Cell Initiation)

  • Cancer cells are initiated when they lose their ability to be controlled within the cell cycle.

  • Skin cancer begins when the normal balance between cell division and cell loss is disrupted.

    • Basal cells divide faster than needed to replenish the cells being shed.

    • With each division, both newly formed cells will often retain the capacity to divide, leading to an increased number of dividing cells.

  • This creates a growing mass of tissue called a "tumor" or "neoplasm."

  • As more and more dividing cells accumulate, the normal organization of the tissue gradually becomes disrupted.

Tumors (Neoplasms)

  • Are masses of cells that are no longer under control of division (Ex: warts).

Cell Differentiation

  • Stem cells

    • An unspecialized cell that can divide without limit as needed.

    • Can, under specific conditions, differentiate into specialized cells.

  • Cell differentiation

    • The process where a cell changes from one type to many different types.

    • Involves differences in morphological structure and physiological function.

  • All organisms begin from a single cell.

Regulation of Cell Differentiation

  • Involves the activation or inactivation of certain genes.

  • Identical cells develop into different types of cells because of genes.

  • There are many genes in a cell, and when one is activated, it turns into a specialized cell (e.g., muscle cells, nerve cells).

Gene Activation Factors

Cells activate specific genes based on two factors:

  1. Their interactions with nearby (neighboring) cells (Cell-cell interaction).

  2. The surrounding environment (extracellular matrix or ECM) (Cell-matrix interaction).

    • ECM provides structural support and plays a critical role in regulating cell differentiation.

    • It is a network of proteins, sugars, and other molecules found outside of cells of tissue.

    • This process helps dedifferentiated cells become differentiated.

Normal vs. Cancerous Cells in Tissues

  • In healthy tissues

    • Cells interact well with each other and the ECM to maintain tissue integrity and function.

  • In cancerous cells (tumor)

    • These interactions can be disrupted, leading to uncontrolled growth and changes in how the cells behave.

  • Note: Loss of responsiveness to the extracellular matrix (ECM) and neighboring cells can lead to key characteristics of tumors.

Cell-Cell Communication

  • Cells within tissues communicate with each other through various signaling pathways.

  • This communication is essential for coordinating the process of cell differentiation.

  • In the context of cancer and tumor formation, several mechanisms can lead to the loss of the ability of cells to sense the ECM and neighboring cells.

    • Sometimes the ability of cells to sense the ECM and neighboring cells is lost, therefore cancer and tumor cells are developed.

Types of Signaling

  • Autocrine signaling: A cell targets itself.

  • Paracrine signaling: A cell signals a nearby cell.

  • Endocrine signaling: A cell targets a distant cell through the bloodstream.

  • Direct signaling: A cell targets a neighboring cell through a gap junction.

Factors That Cause These Disorders (leading to Cancer)

  • Genetic mutations

    • Tumor cells often accumulate genetic mutations that disrupt the normal signaling pathways responsible for ECM and cell-cell communication.

    • These mutations can lead to uncontrolled cell growth and reduced responsiveness to regulatory signals.

  • Altered Cell-ECM interactions

    • Tumor cells may exhibit changes in their interactions with the ECM, which can promote uncontrolled cell division.

  • Loss of contact inhibition

    • Normal cells exhibit a phenomenon called "contact inhibition," using this strategy to stop dividing when they meet neighboring cells.

    • Tumor cells often lose this inhibition, allowing them to grow uncontrollably even near other cells.

  • The loss of responsiveness to the ECM and neighboring cells is a critical aspect of tumor development and progression.

How Cancer Spreads

  • Local invasion: Spreading cancer by local invasion (worse).

  • Metastasis: Travel via blood, lymph to establish colonies in distant tissues.

Evolution of a Cancer

  • Hyperplasia: An increase in the number of cells in a tissue, leading to tissue enlargement. It's often benign but can sometimes lead to cancer.

  • Dysplasia: Abnormal changes in the size, shape, and organization of cells, indicating potential precancerous changes.

  • In situ cancer: Cancerous cells that stay in the place where they started and have not spread to nearby tissues. This is an early stage of cancer.

  • Invasive cancer: Cancer cells that have spread beyond their original site and invaded nearby tissues, indicating a more serious progression that may spread to other body parts.

How Cancers Harm or Kill Us

  • Use nutrients, but do not contribute to function.

  • Expand, causing pressure on other organs, distorting them, or interfering with their blood, lymphatic, or nervous access.

  • Invade and weaken bone.

  • Produce chemicals that disrupt function (anorexia, inflammation, coagulation, pain, blood pressure).

Sexual Reproduction and Meiosis

Sexual Reproduction

  • Sexual reproduction is another way that a new organism can be produced.

  • During sexual reproduction, two sex cells, sometimes called an egg and a sperm, come together.

    • Male sperm + female sperm (egg cell) = zygote \rightarrow embryo \rightarrow baby.

  • Sex cells are formed from cells in reproductive organs.

  • The joining of an egg and a sperm is called fertilization, and the cell that forms is called a zygote.

  • Note: In sexual reproduction, because the egg and the sperm come from two different organisms (in genetic information) of the same species, following fertilization and cell division, a new organism with a unique identity develops.

Diploid Cells and Haploid Cells

  • The number of body cells is much more than sex cells.

  • Your brain, skin, bones, and other tissues and organs are formed from body cells (they are diploid cells).

  • A typical human body cell has 46 chromosomes.

  • The number of total chromosomes in the non-gamete cells of a particular species is called the diploid number for that species.

    • This diploid number of humans is 46, and the diploid number of nematodes is 4.

  • There are two ways cell division can happen in animals and plants, called mitosis and meiosis.

    • When a cell divides by way of mitosis:

      • Generating two clones of itself, each with the same number of chromosomes.

    • When a cell divides by way of meiosis:

      • Producing four cells, called gametes (sperm in males and eggs in females).

    • Note: Unlike in mitosis, the gametes produced by meiosis are not clones of the original cell, because each gamete has exactly half as many chromosomes as the original cell.

The Concept of a Chromosome

  • Before discovering chromosomes, scientists observed genetic material as threads or loops, known as chromatin.

  • Chromatin is made up of a twisted mass of strands.

  • Chromatin is made up of a tangled mass of strands and is visible only when the cell is not dividing.

  • A chromatin is a long strand of DNA with histone proteins attached like beads on a string.

  • Sister chromatids: Identical copies of a chromosome that are created during DNA replication.

  • Homologous chromosomes: Two different chromosomes in a pair that have the same genes but may have different alleles.

Meiosis Stages

  • Meiosis is divided into main stages: Meiosis 1 and Meiosis 2, and both occur after interphase.

1) Interphase (preparation for meiosis)

- **G1 phase**: The cell grows and carries out normal functions.

- **S phase**: DNA is replicated, resulting in two identical copies of each chromosome.

- **G2 phase**: Further growth and preparation for cell division.

2) Meiosis 1 (reduction division)

- **Prophase 1**
    - Chromosomes condense.
    - Homologous chromosomes pair up, and crossing over occurs.

- **Metaphase 1**: Homologous chromosome pairs align at the cell’s equator.

- **Anaphase 1**: Homologous chromosomes are pulled to opposite poles of the cell.

- **Telophase 1**: Chromosomes reach the poles, and the cell divides into two daughter cells.

3) Meiosis 2 (division of haploid cells)

- **Prophase 2**: Chromosomes re-condense in the two haploid cells.

- **Metaphase 2**: Chromosomes align at the equator of each haploid cell.

- **Anaphase 2**: Sister chromatids are separated and pulled to opposite poles.

- **Telophase 2**: Chromatids reach the poles, and the two cells divide, resulting in four haploid daughter cells.

What happens during Prophase 1 of Meiosis 1

1) Chromosome condensation: The chromatin condenses into visible chromosomes, each consisting of two sister chromatids.

2) Homologous chromosome pairing: Homologous chromosomes come together to form pairs in a process called synapsis. Each pair consists of four chromatids.

3) Crossing over: In the paired chromosomes, segments of chromatids may be exchanged between homologous chromosomes.

4) Formation of the spindle apparatus from the centrioles.

5) Nuclear envelope breakdown.

6) Chromosomes attach to spindle fibers.

Metaphase 1 of Meiosis

  • Tetrads align at the cell’s equator (the metaphase plate).

Anaphase 1 of Meiosis

  • Homologous chromosomes are pulled apart and move to opposite poles of the cell.

  • The chromosome number is halved as each daughter cell receives one set of chromosomes.

Telophase 1 of Meiosis

  • Nuclear envelopes may reform.

  • The cell divides into two daughter cells, each with a haploid number of chromosomes.

Meiosis 2

  • Each of the two haploid daughter cells from Meiosis 1 undergo a second division, forming four haploid gametes.

  • Meiosis 2 consists of the following phases:

1) Prophase 2

- Chromosomes condense.

- A new spindle apparatus forms in each of the two haploid daughter cells.

2) Metaphase 2

- Chromosomes align at the metaphase plate in each of the two haploid daughter cells.

3) Anaphase 2

- Sister chromatids are separated and move to opposite poles of each haploid daughter cell.

4) Telophase 2 and Cytokinesis

- Nuclear envelope reforms.

- The two haploid daughter cells from Meiosis 1 each divide into two, resulting in a total of four haploid gametes.

What is the final result of Meiosis?

  • Thus, at the end of Meiosis 2, four non-identical, haploid daughter cells are formed, each having half the chromosome number as the original parent cell.

Main Differences between Meiosis 1 and Meiosis 2

  • In Meiosis 1, a pair of homologous chromosomes separate to produce two diploid daughter cells, each having half the number of chromosomes as the parent cell.

  • In contrast, during Meiosis 2, sister chromatids separate to produce four haploid daughter cells. Also, unlike Meiosis 1, no genetic recombination by crossing over occurs in Meiosis 2.

Purpose of Meiosis

  • Maintaining chromosome number in organisms

    • To maintain chromosome number, gametes formed by meiosis must have half the chromosomes (23) of the parent cell.

    • When the sex cells fuse to form a zygote, the usual chromosome number of 46 chromosomes is restored in the new individual.

    • If the chromosomal reduction process is not maintained, it could cause genetic abnormality in the child.

    • Down syndrome is a genetic disorder caused by the presence of an extra copy of chromosome 21. Children with Down syndrome often experience:
      1) Developmental delays.
      2) Intellectual disabilities.
      3) Distinct facial features.
      4) Various health issues such as heart defects and low muscle tone.

  • Create genetic diversity

    • The exchange of genetic information between the pair of homologous chromosomes allows genetic variation among the population.

    • These variations form the basis of the evolutionary process.

  • Repairs genetic defects

    • Recombination in meiosis helps repair genetic abnormalities in individuals.

    • Recombination in meiosis can replace a genetic defect from a parent, allowing a healthy individual to form.

What would happen if the number of chromosomes were not halved during meiosis before fertilization?

  • Polyploid cells with multiple sets of chromosomes would result.

  • Polyploid cells have more than two complete sets chromosomes, unlike the normal diploid state with two sets.

  • Note: Although plants with polyploid cells are often produced, most animals do not survive with a polyploid cell.

The Necessity of Meiosis in Sexual Reproduction

1) Reduction of chromosome number.

2) Genetic diversity.

3) Adaptation and evolution: The genetic diversity generated by meiosis is essential for adaptation and evolution.

Mendel’s Law of Inheritance

  • Gregor Johann Mendel (1822-1884) is known as the father of genetic science due to his experiments on the pea plant.

  • In 1865, he identified laws of inheritance, but his discoveries were largely ignored by the scientific community, which then favored Darwin's and Lamarck's theories.

  • Consequently, Mendel's work was forgotten until 1900 when his laws were rediscovered by other scientists.

  • Mendel was then recognized as the father of genetic science.

  • It is now understood that the basic principles of heredity he discovered in peas are applicable to other plant and animal species, including humans.

This section discusses:

1) Mendel’s experiments.
2) How these experiments led to the formulation of basic genetic principles known as Mendel's Law.
3) How these principles apply not only to pea plants but also to a wide variety of sexually reproducing organisms, including humans.

Why Mendel Chose the Garden Pea (Pisum sativum) to Study Inheritance

  1. Availability of varieties: This plant was available in many varieties that differed in characteristics, such as the appearance of seeds, pods, flowers, and stems.

    • The seven characters that Mendel chose to follow in his breeding experiments are:

      • Seed shape (round or wrinkled)

      • Seed color (yellow or green)

      • Flower color (purple or white)

      • Pod shape (inflated or constricted)

      • Pod color (green or yellow)

      • Flower position (axial or terminal)

      • Plant height (tall or short)

  2. Reproductive structure: The pea flower produces both male and female gametes in the same flower, which facilitates self-fertilization.

    • In peas, the stamens and the ovaries are enclosed by a modified petal, an arrangement that greatly favors self-fertilization.

    • This allowed Mendel to control the traits studied more easily and to study heritable traits without influence from external factors.

  3. Ease of manipulation: The flowers are large and easy to manipulate, which enabled Mendel to make crosses between flowers easily.

    • Mendel wanted pea plants to self-fertilize, but in other cases, to follow a process of hybridization, or cross-fertilization. He would cross plants that differed concerning some character.

Distinction between Character and Trait

  • Character: A specific feature or attribute of an organism that can be categorized into different types such as morphological and physiological (e.g., flower color, seed shape, or eye color).

    • In Mendel's experiments with pea plants, some characters he studied included:

      • Seed shape (round or wrinkled)

      • Seed color (yellow or green)

      • Flower color (purple or white)

      • Plant height (tall or short)

  • Trait: A variant of a character. Traits can be inherited and are determined by genes. They can be dominant and recessive.

    • For instance, in the case of flower color in pea plants, the trait “purple flowers” and the trait “white flowers” are two different expressions of the character “flower color.”

Law of Segregation

  • Mendel's work on the inheritance of single traits revealed the law of segregation.

  • One of the single factor crosses in which Mendel focused was on the character height:

    1) Mendel crossed tall and dwarf plants.
    2) It was observed that all plants of the F1 generation were tall.
    3) In the F2 generation, three-fourths of the plants were tall, and one-fourth were dwarf. Interestingly, the dwarf trait reappeared in the F2 offspring.

  • Mendel's data analysis revealed three key ideas about trait inheritance:

    1) Traits may exist in two forms: dominant and recessive.
    2) Each character is regulated by genes, which exist in 2 forms called alleles controlling the trait.
    3) During meiosis, two alleles separate, leaving each gamete with one allele.

Alleles, Dominance, and Recessiveness

  • Allele: A part of a gene that controls a heritable trait. An individual inherits two alleles for each character, one from each parent.

  • Dominant alleles:

    • Show their effect even if the individual only has one copy (heterozygous).

    • Denoted by capital letters (e.g., 'B' for brown eyes).

    • For example, only one brown eye allele is needed to have brown eyes; two copies will also result in brown eyes.

  • Recessive alleles:

    • Are masked by a dominant allele in heterozygous individuals.

    • Only expressed when two copies are present (homozygous recessive).

    • Denoted by lowercase letters (e.g., 'b').

Genetic Makeup: Homozygous and Heterozygous

  • The genetic makeup of an individual in terms of the alleles controlling a trait is either homozygous or heterozygous.

  • Homozygous: Individuals have two identical alleles for a gene.

    • Homozygous dominant: Two identical dominant alleles (e.g., BBBB).

    • Homozygous recessive: Two identical recessive alleles (e.g., bbbb).

  • Heterozygous: An individual having two different alleles for a particular gene: one dominant allele and one recessive allele (e.g., BbBb).

    • Heterozygotes always show the dominant trait because the dominant allele masks the recessive one.

Law of Segregation (Continued)

  • Formation of gametes in the F1 by meiosis:

    • The two alleles segregate or separate from each other.

    • Each gamete carries only one allele for a particular gene.

  • The dominant trait is expressed in the F1 generation.

  • The dominant allele masks the effect of the recessive allele.

  • The recessive trait is still present in the genetic makeup (heterozygous) but it is not visibly expressed.

Genotype vs. Phenotype

  • Genotype: Describes an organism’s genetic makeup.

    • For example: BBBB (homozygous dominant), BbBb (heterozygous), bbbb (homozygous recessive).

  • Phenotype: Describes an organism’s observable characteristics (physical expression of the genotype).

    • For example: Purple, Purple, White (for flower color based on corresponding genotypes).

Punnett Square

  • A visual tool used in genetics to predict possible allele combinations from a cross between two individuals.

  • By analyzing the completed Punnett square, you can determine the offspring’s genotypes and phenotypes.

  • It illustrates segregation principles in offspring.

Test Cross

  • A cross used to determine an individual’s unknown genotype (typically a dominant phenotype, to distinguish between homozygous dominant and heterozygous).

Mendel's Law of Independent Assortment

  • We have discussed single factor crosses so far (e.g., Aa×AAAa×AA, Aa×aaAa×aa, Aa×AaAa×Aa).

  • The next big question is whether or not the inheritance of multiple phenotypes are linked or inherited independently.

  • Possible patterns of inheritance for two or more characters (e.g., BBAa×bbAABBAa×bbAA, BbAa×BbAABbAa×BbAA).

  • There are two alternative hypotheses:

    1) Hypothesis (1) Prediction of linked (dependent) assortment:

    - The alleles are physically linked together.

- For example, an allele that controls flower color (FF) is physically linked to an allele that controls seed color (SS).

    2) Hypothesis (2) Prediction of independent assortment:

    - The alleles are not physically linked.

  • What if a dihybrid cross is conducted?

    • All combinations of alleles for different traits are possible in gametes: FSFS, FsFs, fSfS, and fsfs.

    • Independent assortment (for two traits, e.g., purple flower/yellow seed and white flower/green seed) would yield phenotypic ratios like:

      • 9 purple-flower/yellow-seed

      • 3 purple-flower/green-seed

      • 3 white-flower/yellow-seed

      • 1 white-flower/green-seed

  • The correct and widely accepted hypothesis is “independent assortment.”

Genetic Linkage

  • The tendency of nearby genes on the same chromosome to be inherited together.

  • Linked = dependent assortment (genes are close together on the same chromosome).

  • Not linked = independent assortment (genes are on different chromosomes or far apart on the same chromosome).

  • The relationship between genes and chromosomes was discovered after Mendel’s principles.

The Chromosome Theory of Inheritance

  • This theory explains how traits are inherited from parents to offspring through genes located on chromosomes.

  • Mendel’s principles provided the initial understanding of heredity:

    1) Law of Segregation

    2) Law of Independent Assortment

  • The discovery of chromosomes: After Mendel, scientists studied heredity, but the solid connection between genes and chromosomes was established in the early 20th century.

  • Key ideas of the chromosome theory of inheritance are:

    1) Chromosomes carry genes.

    2) Genes are inherited via chromosomes.

    3) Chromosomes come in pairs.

Autosomes and Sex Chromosomes

  • Autosomes: The non-sex chromosomes in an organism’s genome.

    • In humans, autosomes are the 2222 pairs of chromosomes that do not determine an individual’s sex.

  • Sex chromosomes: Chromosomes responsible for determining an individual's sex.

Sex Chromosome Systems: Diversity and Mechanisms Across Organisms

  • XX/XY system:

    • Found in mammals and some plants.

    • XXXX represents the female sex chromosome pair; XYXY represents the male.

    • Females are XXXX (homogametic), and males are XYXY (heterogametic).

    • The X chromosome in females carries genetic information necessary for female development.

  • ZW/ZZ system:

    • Found in birds and some fish.

    • Females are ZWZW (heterogametic), and males are ZZZZ (homogametic).

    • The Z chromosome is present in both sexes.

  • Haplodiploidy system:

    • Found in insects like bees, ants, and wasps.

    • Sex is determined by the number of chromosome sets.

    • Males are haploid (one set of chromosomes, e.g., 1616 in bees) and develop from unfertilized eggs.

    • Females (worker bees and queen bees) are diploid (two sets of chromosomes, e.g., 3232 in bees) and develop from fertilized eggs.

  • XO system:

    • Operates in many insects like grasshoppers.

    • Females have two X chromosomes (XXXX).

    • Males have only one X chromosome (XOXO), where 'O' represents the absence of a second sex chromosome.

  • Temperature-Dependent Sex Determination (TSD):

    • Found in certain reptiles (e.g., American alligator) and fish.

    • Sex is controlled by environmental factors, primarily the incubation temperature of the eggs.

    • Example: American alligator eggs incubated at 3333 degrees Celsius produce nearly all males; significantly below 3333 degrees Celsius produces nearly all females.

  • Sex determination in plants:

    • Most species of flowering plants (including pea plants) have a single type of diploid plant that produces both male and female gametes (monoecious).

    • However, sex chromosomes, designated X and Y, are responsible for sex determination in many plant species, where the male plant is XYXY and the female plant is XXXX.

Exploring the Chromosomal Basis of Inheritance: Morgan's Fruit Fly Experiments

  • By the early 20th century, Mendel's principles of inheritance were well-known, but the physical basis of heredity (how genes were transmitted) was not understood.

  • Thomas Hunt Morgan (born Sept. 25, 1866, Lexington, Kentucky, USA) aimed to understand how genes are linked to chromosomes and how traits are inherited, specifically addressing the correlation between a genetic trait and sex inheritance.

Why Fruit Flies (Drosophila melanogaster)?

  • Morgan selected fruit flies for his research due to several advantageous characteristics:

    • Large number of offspring: Allows for statistically significant results.

    • Short life cycle (∼2∼2 weeks): Enables quick generation turnover and observation of multiple generations.

    • Easy to breed in lab conditions.

    • Relatively few chromosomes: Fruit flies have four pairs in total, which are large and easily observable under a microscope.

    • Observable traits: Possess distinct and easily distinguishable traits like eye color, wing shape, and body color.

  • Morgan's research led to significant discoveries about inheritance and chromosomes.

Experiment 1: Discovery of the White-Eyed Mutant

  • Morgan started with wild-type fruit flies, which typically have red eyes, the standard trait.

  • After two years of studying numerous flies, Morgan discovered a male fly with white eyes, a rare deviation from the typical red-eyed flies.

  • He then crossed this white-eyed male with a red-eyed female to observe how this trait would be inherited.

    • Cross 1 (Parental generation – P): White-eyed male ×× Red-eyed female.

      • F1 generation (first offspring): All offspring had red eyes, demonstrating that the red-eye trait was dominant.

    • F2 generation (second cross): He crossed F1 red-eyed males and females.

      • Result: In the F2 generation, the flies showed a 3:13:1 ratio of red eyes to white eyes, but crucially, all white-eyed flies were males. Red-eyed flies included both males and females.

      • Conclusion:

        • Males typically have two sex chromosomes: X and Y.

        • Females have two X chromosomes.

        • The X chromosome contains many genes responsible for various traits, like other chromosomes.

        • The Y chromosome in males carries few or no homologous genes compared to the X chromosome relevant to certain traits.

        • The gene that controls eye color is located on the X chromosome.