Essentials of Genetics Chapter 2: Mitosis and Meiosis

Introduction to Genetic Continuity

• All living organisms contain genetic material made of the nucleic acid DNA ($D N A$), with the exception of certain viruses.
• An organism’s $D N A$, which contains its genes, is organized into structural units called chromosomes.
• In eukaryotic organisms, genetic continuity of nucleated cells involves two primary processes:
  • Mitosis: Results in production of daughter cells.
  • Meiosis: Results in production of sex cells, which may be gametes (animals) or spores (plants/fungi).
• While mitosis and meiosis involve similar mechanical processes, they lead to fundamentally different outcomes regarding genetic content.
• Mitosis leads to the production of two cells, each containing the same number of chromosomes as the parent cell ($2n$).
• Meiosis reduces the genetic content and lead to the production of sex gametes, which contain exactly half the number of chromosomes ($n$).
• Chromosomes are visible as condensed structures only during the processes of mitosis and meiosis.
• When not dividing, chromosomes exist in an uncoiled state known as chromatin, which forms a diffuse network within the cell nucleus.

Cellular Structure and Genetic Function

• The use of transmission electron microscopy allowed scientists to observe the highly varied and organized internal structure of the cell.
• Electron microscopy revealed various components including membranes, organelles, microtubules, granules, and filaments.
• Specific cell components directly or indirectly involved with genetic processes include the nucleolus, ribosomes, and centrioles.
• Specialized organelles, specifically mitochondria and chloroplasts, contain their own unique genetic information independent of the nucleus.
• All cells are surrounded by a plasma membrane which:
  • Defines the cell boundary.
  • Delimits the cell from its external environment.
  • Controls the movement of materials into and out of the cell.
• Plant cells possess an outer covering in addition to the plasma membrane known as the cell wall, which is primarily composed of the polysaccharide cellulose.
• Animal cells are surrounded by a cell coat called the glycocalxy:
  • The glycocalyx consists of glycoproteins and polysaccharides.
  • Its chemical composition differs from that of plants and bacteria.
  • It provides biochemical identity at the cell surface.
  • Specific cell-surface markers such as $A B$, $R h$, and $M N$ antigens found on blood cells serve as recognition sites.

Eukaryotic vs. Prokaryotic Cellular Organization

• There are two main types of cells based on their structural complexity:
  • Prokaryotic Cells:
    • Nonnucleated cells.
    • Include bacteria and archaea.
    • Lack a nuclear envelope and membranous organelles.
    • Genetic material consists of a long, circular $D N A$ molecule compacted into an area called the nucleoid.
    • $D N A$ does not undergo the extensive coiling characteristic of eukaryotic cells because it is not as extensively associated with proteins.
    • Prokaryotic cells lack a distinct nucleolus but contain genes necessary for $r R N A$ synthesis.
  • Eukaryotic Cells:
    • Nucleated cells.
    • Include protists, plants, fungi, and animals.
    • Defined by the presence of a nucleus and membranous organelles.
    • The membrane-bound nucleus houses genetic material ($D N A$) complexed with proteins into thin fibers called chromatin.
    • Nucleus contains the nucleolus: the location where ribosomal $R N A$ ($r R N A$) is synthesized and initially assembled.
    • The Nucleolus Organizer Region ($N O R$) refers to the portions of $D N A$ that encode $r R N A$.

The Eukaryotic Cytoplasm and Organelles

• Cytoplasm: The remainder of the cell within the plasma membrane, excluding the nucleus.
• Cytosol: The colloidal material surrounding the cellular organelles.
• Cytoskeleton: A lattice of support for structures within the cell, composed of microtubules and microfilaments.
  • Microtubules are made of the protein tubulin.
  • Microfilaments are derived from the protein actin.
• Endoplasmic Reticulum ($E R$):
  • A membranous organelle that compartmentalizes the cytoplasm and increases cellular surface area.
  • Smooth $E R$: The site of lipid (fatty acid) synthesis.
  • Rough $E R$: Studded with ribosomes; serves as the site of protein synthesis.
• Ribosomes: The sites where genetic information in messenger $R N A$ ($m R N A$) is translated into proteins.
• Mitochondria:
  • Found in most eukaryotic cells (both animal and plant).
  • The site of $A T P$ synthesis.
  • The site of oxidative phases of cell respiration.
  • Contains its own distinct $D N A$.
• Chloroplasts:
  • Found in plants, algae, and some protozoans.
  • The site of photosynthesis.
  • Contains its own distinct $D N A$.
• Centrioles:
  • Cytoplasmic bodies located within the centrosome in animal and plant cells.
  • They organize the spindle fibers used in meiosis and mitosis.
• Spindle Fibers:
  • Composed of microtubules consisting of polymers of the protein tubulin.
  • Essential for the movement of chromosomes as they separate during cell division.

Chromosome Classification and Morphology

• Centromere: The constricted region on a chromosome.
• The location of the centromere dictates the appearance of the chromosome and serves as the basis for classification:
  • Metacentric: Centromere is located in the middle.
  • Submetacentric: Centromere is located between the middle and the end.
  • Acrocentric: Centromere is located close to the end.
  • Telocentric: Centromere is located at the very end.
• During anaphase, the shape of the chromosome is determined by the position of the centromere during metaphase.
• Each chromosome in a dividing cell is a double structure consisting of a pair of sister chromatids joined by a common centromere.

Homologous Chromosomes and Diploidy

• Somatic cells (body cells) derived from the same species have the same number of chromosomes, known as the diploid number ($2n$).
  • Humans have a $2n$ number of $46$ chromosomes.
• Chromosomes exist in pairs called homologous chromosomes (exceptions include sex chromosomes and those in certain microbes).
• Karyotype: The total number and appearance of chromosomes in the nucleus of a eukaryotic cell.
• Haploid number ($n$):
  • Equal to one-half of the diploid ($2n$) number.
  • The genetic information in a haploid set of chromosomes constitutes the genome of the species.
• Table 2.1: Haploid Numbers ($n$) for Various Organisms:
  • Black bread mold (Aspergillus nidulans): $8$
  • Broad bean (Vicia faba): $6$
  • Chimpanzee (Pan troglodytes): $24$
  • Corn (Zea mays): $10$
  • Cotton (Gossypium hirsutum): $26$
  • Fruit fly (Drosophila melanogaster): $4$
  • Garden pea (Pisum sativum): $7$
  • House mouse (Mus musculus): $20$
  • Human (Homo sapiens): $23$
  • Pink bread mold (Neurospora crassa): $7$
  • Roundworm (Caenorhabditis elegans): $6$
  • Yeast (Saccharomyces cerevisiae): $16$
  • Zebrafish (Danio rerio): $25$
• Homologous chromosomes share identical genetic similarities, including identical gene sites along their lengths called loci ($locus$ singular).
• Biparental inheritance: In diploid organisms, inheritance comes from two parents (ovum and sperm).
  • Each diploid cell contains two copies of each gene.
  • Alleles are alternative forms of the same gene found at the same locus.
• Sex-determining chromosomes are nonhomologous:
  • Females: $X X$.
  • Males: $X Y$.
  • The $Y$ chromosome is smaller and lacks most of the gene loci contained on the $X$ chromosome.

Mitosis: The Process of Nuclear and Cytoplasmic Division

• Mitosis is critical for all eukaryotic organisms:
  • In single-celled fungi, protozoa, and algae, it serves as the basis for asexual reproduction.
  • In multicellular organisms, it is responsible for growth, cell replacement, and wound healing.
• Zygote: A single-celled fertilized egg.
• The division process involves two distinct parts:
  • Karyokinesis: Nuclear division, where genetic material is evenly divided into two daughter nuclei.
  • Cytokinesis: Cytoplasmic division, which partitions the cellular volume and encloses each new cell in a plasma membrane.

Interphase and the Cell Cycle

• Cell Cycle: The continuous alternation between the division (mitosis) and nondivision (interphase) of cells.
• Interphase: The initial stage of the cell cycle and the interval between divisions.
  • Stages: $G_1$, $S$, and $G_2$.
  • $S$ Phase: The period during which $D N A$ replication occurs for each chromosome.
  • $G_1$ and $G_2$ (Gap I and Gap II): Occur in the cytoplasm. No $D N A$ synthesis occurs. These are phases of metabolic activity, cell growth, and differentiation.
  • By the end of $G_2$, the cell has doubled in size, $D N A$ is replicated, and mitosis is initiated.
• $G_0$: A point in the $G_1$ phase where cells withdraw from the cell cycle and enter a nondividing but still metabolically active state.

Stages of Mitosis

• Prophase:
  • Chromosomes condense and become visible from chromatin fibers.
  • Centrioles (in animal cells) divide and move to opposite poles.
  • The nuclear envelope breaks down.
  • The nucleolus disintegrates.
  • Sister chromatids (genetically identical parts of each chromosome) are visibly connected at the centromere.
  • Cohesin: A protein complex formed during $S$ phase that holds sister chromatids together.
• Prometaphase:
  • Period of chromosome movement toward the equatorial plane.
  • Spindle fibers bind to kinetochores (protein layers at the centromere) to move chromosomes.
• Metaphase:
  • Chromosomes reach a configuration where they are aligned at the metaphase plate (equatorial plate).
  • Cohesin is degraded by the enzyme separase, except at the centromere.
  • The protein shugoshin prevents the degradation of cohesin at the centromere region during this stage.
• Anaphase:
  • Sister chromatids separate (disjunction) and are pulled toward opposite poles.
  • Once separated, they are no longer chromatids but daughter chromosomes.
  • Complete disjunction occurs as shugoshin degrades and the remaining cohesin complex is cleaved by separase.
• Telophase:
  • Final stage of mitosis where two complete sets of chromosomes are at each pole.
  • Cytokinesis divides the cytoplasm.
  • Chromosomes uncoil back into chromatin.
  • The nuclear envelope reforms.
  • Spindle fibers disappear and the nucleolus reforms.
  • The cell re-enters interphase.

The Regulation of the Cell Cycle

• The cell cycle is genetically regulated and highly conserved throughout evolution.
• Disruption of this regulation can lead to uncontrolled cell division, which characterizes malignancy.
• Master Control Molecules:
  • Kinases: Enzymes produced by certain genes that serve as master controls.
  • Cyclins: Proteins that bind with kinases, activating them at specific appropriate times during the cycle.
• Checkpoints: Three major points ($G_1$, $G_2$, and $M$) where the cell cycle is monitored.
  • If errors are not recognized and stopped at these checkpoints, tumor formation may result.
  • If the cycle is arrested at a checkpoint, the cell is removed from the population of dividing cells to prevent malignancy.

Meiosis: Producing Haploid Gametes and Spores

• Meiosis creates gametes or spores containing only one haploid ($n$) set of chromosomes.
• It reduces the amount of genetic material by one-half ($2n$ to $n$).
• Fertilization restores the diploid number ($2n$).
• Meiosis maintains genetic continuity from generation to generation and generates genetic variation.
• Genetic variation is enhanced by crossing over:
  • Occurs between homologous chromosomes.
  • Results in genetic exchange between members of homologous pairs.
  • Creates mosaic chromosomes composed of both maternal and paternal homologs.

Stages of Meiosis I: The Reductional Division

• Meiosis I involves the separation of homologous pairs.
• Prophase I:
  • The diploid cell duplicates genetic material.
  • Synapsis: Homologous chromosomes pair up.
  • Bivalent: Each synapsed pair of homologs.
  • Tetrad: A unit consisting of two pairs of sister chromatids (four chromatids total).
  • Chiasma: The region where chromatids remain intertwined; the point where nonsister chromatids have undergone genetic exchange via crossing over.
  • At the end of Prophase I, the nuclear envelope and nucleolus break down, and the centromeres of the tetrad attach to spindle fibers.
• Metaphase I:
  • Chromosomes are at maximum shortness and thickness.
  • Terminal chiasmata hold nonsister chromatids together.
  • Tetrads align randomly on the metaphase plate.
• Anaphase I:
  • Homologous chromosomes separate (disjunction).
  • One-half of each tetrad, known as a dyad, is pulled to opposite poles.
  • Nondisjunction may occur if separation fails.
• Telophase I:
  • Nuclear membranes reappear around the dyads.
  • The nucleus enters a short interphase; chromosomes do not replicate because they already consist of sister chromatids.

Stages of Meiosis II: The Equational Division

• Meiosis II is similar to mitosis as sister chromatids separate.
• Prophase II: Each dyad is composed of one pair of sister chromatids attached by a common centromere.
• Metaphase II: Centromeres are positioned at the metaphase plate.
• Anaphase II: Centromeres divide, and sister chromatids (now monads) are pulled to opposite poles.
• Telophase II: One member of each homologous chromosome (monad) is at each pole.
• Cytokinesis: Results in four haploid gametes from the original single meiotic event.

Spermatogenesis and Oogenesis: The Development of Gametes

• Spermatogenesis (Male Gamete Production):
  • Occurs in the testes.
  • Begins with an undifferentiated germ cell called a spermatogonium.
  • The spermatogonium enlarges to become a primary spermatocyte.
  • The primary spermatocyte undergoes Meiosis I to produce two haploid secondary spermatocytes.
  • Secondary spermatocytes undergo Meiosis II to produce four haploid spermatids.
  • Spermatids undergo developmental changes (spermiogenesis) to become motile spermatozoa (sperm).
• Oogenesis (Female Gamete Production):
  • Occurs in the ovaries.
  • Begins with an undifferentiated germ cell called an oogonium, which becomes a primary oocyte.
  • Daughter cells receive equal amounts of genetic material but unequal amounts of cytoplasm.
  • Meiosis I: Almost all cytoplasm from the primary oocyte is concentrated into one daughter cell (the secondary oocyte); the other cell, with very little cytoplasm, becomes the first polar body.
  • Meiosis II: The secondary oocyte divides unequally, producing an ootid (with the bulk of the cytoplasm) and a second polar body.
  • The ootid differentiates into a mature ovum.
  • The secondary division is typically completed only after fertilization.

Genetic Variation through Meiosis

• Meiosis is critical for sexual reproduction in diploid organisms.
• Plants produce haploid spores through meiosis, which later turn into gametes.
• Diploid organisms store genetic information in homologous pairs.
• Variation mechanisms include:
  • Crossing Over: Reshuffles alleles between maternal and paternal homologs during Prophase I.
  • Independent Assortment: Chromosomes segregate and assort independently into gametes during the meiotic divisions.
  • These processes result in a vast amount of genetic variability in the resulting gametes.