9 Mitosis, Meiosis and Gene Aberration (DIY)

• Variation in chromosomal structure (Mechanism 1)

  Chromosomal deletions and duplications

  • Can occur during crossing over
  • Non-sister chromatids of homologous chromosomes may break and re-join at incorrect places such that one chromatid may give up more genes than it receives
  • Products of such an unequal crossover are one chromosome with a deletion mutation and one with a duplication mutation
• Variation in chromosomal structure (Mechanism 2)

  Chromosomal inversion and translocation

  • Result in disease even though the amount of chromosomal material remains the same
  • May still alter the phenotype because the gene’s expression can be influenced by its new location among neighbouring genes
• Significance of variation in chromosomal structure

  • Phenotypic abnormalities that result are usually due to the reduced or additional genetic material/ dosage reflected in chromosomal deficiencies and duplications respectively
  • Chromosome deletions frequently result in zygotic loss, stillbirths or infant deaths
• E.G: Deletion in Chromosomal Structure (Cri-du-chat syndrome)

  • Due to deletion in the short arm of chromosome 5
  • Child born is physically and mentally retarded, has a small head, broad face and saddle nose, widely shaped eyes, unusual facial features and a cry that sounds like the mewing of a distressed cat
  • Most cases are NOT inherited 
  • Result from a chromosomal deletion that occurs as a random event during the formation of gametes or in early foetal development
• E.G: Translocation in Chromosomal structure (Chronic Myelogenous Leukemia)

  • In CML, most of the chromosome 22 has been translocated onto the long arm of chromosome 9
  • Resultant chromosome 22 is called “Philadelphia chromosome” → chromosome is found only in tumour cells of a person with CML
  • Translocation brings 2 genes next to each other and genes are transcribed & translated as one protein
  • Protein causes increased cell proliferation and reduced apoptosis (programed cell death) → cancer
  • CML affects the stem cells that develop into WBCs → tumour cells mature abnormally but proliferate rapidly
• Variation in Chromosomal Number (Mechanism 1 - ANEUPLOIDY)

  • A condition where the cell does not have a chromosome number that is a multiple of the haploid number
  • If chromosome is present in triplicate → TRISOMIC
  • If cell is missing a chromosome → MONOSOMIC
  • A result of non-disjunction (failure of homologous chromosomes/ sister chromatids to separate properly during nuclear division)
  • If occurs in meiosis, mitosis will subsequently transmit the anomaly to ALL embryonic cells
  • Can also occur during mitosis - in embryonic development will be passed on to a large number of cells
• E.G.: Aneuploidy (Down Syndrome - Trisomy 21)

  • A result of an extra chromosome 21 → each body cell has a total of 47 chromosomes
  • Mostly resulted from non-disjunction during meiosis I
  • Includes characteristic facial features, short stature, heart defects, susceptibility to respiratory infection and mental retardation
  • Most are sexually underdeveloped and sterile
• Variation in Chromosomal Number (Mechanism 2 - POLYPLOIDY)

  • A condition where there are 3 or more times the haploid number of chromosomes in the nucleus
  • Can result from:
  • Non-disjunction of entire chromosome sets in mitosis → producing 4n somatic cells
  • Non-disjunction of entire chromosome sets in meiosis → producing 2n gametes formed
  • 2n gamete fuse with 2n gamete → 4n zygote
  • 2n gamete duse with n gamete (normal) → 3n zygote
  • More common among PLANTS than animals
  • Reasons unclear
  • E.g.: Tetraploid Mammal (Desert Rat)
• Mitosis (Intro)

  • A form of nuclear division in eukaryotic cells which produces 2 daughter nuclei containing identical sets of chromosomes as the parental cell nucleus
  • Begins after interphase (in the right conditions)
  • Usually followed immediately by cytokinesis, during which an equal division of the cytoplasm of the parent cell and formation of the cell surface membrane and cell wall results in the formation of  daughter cells
  • 4 Main stages: PMAT
• Mitosis (1. Early Prophase)

  • Usually the longest phase of mitosis
  • Starts when chromatin condenses
  • Centrosome (mitotic spindles complex) move to opposite parts of the cell
  • Mitotic spindles form
  • Nucleolus begins to disappear and nuclear envelope begins to disintegrate
  • Chromatin in the process of condensing into a chromosome
• Mitosis (2. Late Prophase)

  • Chromatin is fully condenses into chromosomes
  • Appears as 2 sister chromatids joined together at the centromere
  • Centrioles (in centrosome) migrate to opposite poles of the cell
  • Spindle fibres extend from each pole towards the kinetochores and the middle region of the cell (metaphase plate)
  • Kinetochore microtubules attach to centromeres of the chromosomes → moves chromosomes along the metaphase plate
  • Asters are radial arrays of shorter microtubules that extend from the centrosome
  • Nucleolus gradually disappears and nuclear envelope disintegrates
• Mitosis (3. Metaphase)

  • Centrioles located at the poles of the cell
  • Spindle is completely formed
  • Kinetochore microtubules are attached to the centromeres of the chromosomes
  • All chromosomes attached to kinetochore microtubules from opposite poles
  • Nucleolus -
  • Chromosomes are aligned at the equator/ metaphase plate in a single row (Random order)
  • They line up in a single file along the metaphase plate
• Mitosis (4. Anaphase)

  • Shortest phase in Mitosis
  • Spindle fibres (non-kinetochore microtubules elongate and slide in opposite direction due to the actions of motor proteins
  • The 2 poles move further apart
  • Kinetochore microtubules/ spindle fibres shorten
  • This separates sister chromatids, now called daughter chromosomes by pulling to opposite poles
  • Daughter chromosomes are led by their centromeres resulting in the characteristic ‘V’ shape of chromosomes seen in anaphase
  • Nucleolus -
  • Centromere of the chromosome divides into 2
  • ** BE CAREFUL NOT TO USE SPLIT
• Mitosis (5. Telophase)

  • 2 nuclei forming in one cell
  • Spindle fibres disintegrate
  • Nuclear membrane reforms around the chromatin at each pole and the nucleolus reappears
  • Daughter chromosomes reach the poles of the cell, and will decondense and lengthen into chromatin
  • Chromosomes will then appear diffused and are not clearly visible
  • Cleavage furrow (in animal cells)/ Cell plate (in plant cells) start to form
• Cytokinesis (Animal)

  • Cell surface membrane begins to invaginate towards the region previously occupied by the equator/ metaphase plate, forming a cleavage furrow due to contracting microfilaments (“drawstring effect”)
  • Cleavage furrow deepens until the parent cell is pinched into 2, producing 2 completely separated cells each with its own nucleus, cytosol and organelle
• Cytokinesis (Higher plant)

  • A series of vesicles (derived from the Golgi apparatus) containing e.g. pectin, move to the equator/ metaphase plate of the cell and fuse to form cell plate
  • Membrane of the vesicles form the cell surface membranes of the daughter cells
  • Cell plate eventually fuses with the parent cell wall and cell surface membrane separating the daughter cells
• Significance of Mitosis (1 - Maintaining Genetic Stability)

  • Mitosis produces 2 daughter nuclei → each have the same number and same types of chromosomes as the parent cell
  • Both nuclei were derived from the parental chromosomes by exact replication of their DNA
  • Mitosis produces daughter cells that are genetically identical to their parent cell
  • No introduction of genetic variation → maintains genetic stability within the populations of cells derived from the same parental cells
  • Will not result in rejection by the body immune system
  • Helps in recognising self versus non-self cells
• Significance of Mitosis (2 - Growth)

  • An increase in number of cells or size of cells
  • The number of cells within the organism increases and the new cells produced are genetically identical to the existing cells
• Significance of Mitosis (3 - Regeneration and Cell Replacement)

  • When damaged tissues are repaired, the damaged cells are replaced by cells that are genetically identical to the original cells
  • Helps in cell replacement and regeneration of missing parts, to varying degrees in multicellular organisms
  • E.g. Regeneration of tails in lizards and arms in starfish
• Significance of Mitosis (4 - Asexual Reproduction)

  • An organism replicates itself without the production of eggs or without fertilisation
  • When a single parent produces offspring genetically identical to itself
  • Propagation by asexual means involving mitotic divisions of cells
  • Advantageous in stable environments where the offspring receive a set of genes form the parent who has survived and reproduced under the same conditions
  • Offspring will be suitably adapted to the same conditions that have allowed the parent to thrive in
  • Population can reproduce very rapidly in these ideal conditions
• Interphase (Non-dividing phase of the cell; longest phase of cell cycle)

  • Cell produces many materials and organelles required for carrying out all its functions
  • Cell replicates its DNA (during S phase of Interphase) to prepare for nuclear division
  • Consists of the:
  • G1 phase
  • Synthesis phase (S phase)
  • G2 phase
• G1 phase (period of cell growth before the DNA is replicated)

  • Intensive cellular synthesis:
  • Organelle synthesis
  • RNA synthesis
  • Protein synthesis
  • Cell moves from G1 phase to S phase (in the presence of certain signals, DNA replication occurs)
• Synthesis phase (DNA replication)

  • Semi-conservative DNA replication occurs:
  • DNA replicate → amount of DNA in the cell doubles
  • Centrioles (in cells possessing them) replicate
  • Centromeres are the microtubule organising centre (MTOC) → centrosome = centrioles + proteins
• G2 phase (Further growth and preparation for mitosis)

  • Intensive cellular synthesis (in preparation for mitosis)
  • Organelle synthesis
  • Synthesis of spindle proteins
  • Microtubules begin to form
• Importance of cell-cycle checkpoints

  • Provides sufficient time for cellular activities to occur within a phase
  • Enables a cell to ensure that important processes, such as DNA replication, are completed properly
  • Prevents the transmission of mutations to daughter cells, which may lead to cancer
• Chromosome ROLE

  • Chromosomes carry the hereditary material (DNA) in cells
  • Passed on to the next generation through cell division
  • Found in the nucleus of dividing cells during some stages of mitosis and meiosis
  • After DNA has replicated during interphase, the chromatin starts condensing during prophase
  • Chromatin reaches the highest level of compaction during anaphase
  • Sister chromatids contain identical DNA molecules as they are replicated from the same DNA molecule
  • If they undergo crossing over → non-identical
  • After replication, 2 sister chromatids are held together in the centromere
• Eukaryotic Chromosome Structure

  • DNA: double-stranded, helical molecule found within the nucleus of each cell
  • Carries the genetic information that codes for proteins necessary for cells to perform their functions/ for division
  • Chromatin: When a cell is not dividing, chromosomes exist in their dispersed, uncondensed form, as a mass of long, thin, thread-like fibres
  • DNA winds around an octamer formed by 8 histone proteins forming a nucleosome
  • Chromosome: Condensed chromatin via coiling/ folding many times upon itself
  • Thicker, shorter and more visible structure
• Haploid

  • Describes a nucleus, cell or organism that contains only one complete set of chromosomes
  • Represented as n (the haploid number of chromosomes for the gametes in human in 23)
  • Gametes are generally haploid (sex cells)
• Diploid

  • Describes a nucleus, cell or organism with 2 complete sets of chromosomes, where each chromosome in the pair comes from either parent (maternal & paternal)
  • Most eukaryotic organisms exist in a diploid condition
  • Somatic cells are diploid (non-gametic)
  • Represented as 2n, where n represents 1 complete set of chromosomes
  • Diploid number refers to the number of chromosomes within the 2 sets of chromosomes
• Fertilisation

  • Fusion of a haploid sperm and haploid egg during fertilisation results in the formation of a diploid zygote
  • After fertilisation, the zygote undergoes a process of nuclear division called mitosis
  • Generates cells that are genetically identical to the original zygote
  • Chromosomes bear the ancestral genes that represent the maternal and paternal family lines
  • Cells are stimulated to differentiate into specialised cells that form the organism
• Homologous Chromosomes

  • Chromosomes having the same size, shape, centromere position, staining pattern and position of genes (or gene loci)
  • Each member = a HOMOLOGUE
  • Characteristics:
  • Similar in size, shape, centromere position and staining pattern
  • One homologue originates from the male parent & the other from the female parent
  • Have the same genes at corresponding loci
  • Locus: the position of a gene in a chromosome
  • Alleles: alternative forms of a gene → occupy the same locus on a pair of homologous chromosomes
  • Chromosome X and Y do not form homologous pairs
• Meiosis (Intro)

  • A form of nuclear division that occurs in sexually reproducing organisms
  • Each parental cell produces four haploid genetically different daughter nuclei via meiosis
  • “reduction division” - because resultant daughter cells have half as many chromosomes as the parental cells
  • Nucleus of resultant daughter cells will have one set of chromosomes (no homologous pairs)
  • Haploid (n) in nature
  • 2 haploid gametes fuse during fertilisation to form a zygote (or fertilised egg)
  • Results in offspring that have 2 sets of chromosomes, one set from each parent
• Meiosis I (1. Interphase)

  • Events during interphase (similar to mitosis)
  • Undergo semi-conservative DNA replication and sister chromatids are formed during the Synthesis (S) phase of interphase
  • Intensive cellular synthesis occurs during the G1 & G2 phases of the cell cycle, in preparation for meiosis
• Meiosis I (Early Prophase I)

  • Chromatin coils, shortens and thickens into a condensed chromosome
  • Homologues (homologous chromosomes) pair up via the process of synapsis to form bivalents (this process is independent of spindle fibres)
  • In every pair, one homologue comes from the father and the other homologues from the mother
  • Spindle formation begins
  • Nucleolus begins to disappear and nuclear envelope begins to disintegrate
  • Centrioles begin to migrate to opposite poles of the cell
• Meiosis I (Late Prophase I)

  • Crossing over occurs between the non-sister chromatids of homologous chromosomes
  • Chiasmata: sites where non-sister chromatids of homologous chromosomes break and rejoin
  • Exchange of equivalent portion of genetic material/ allele between non-sister chromatids
  • Results in new combinations of alleles on the chromosome → contributes to diversity and variation
  • Bivalents → tetrads
  • Centrioles continue to migrate to opposite poles of the cell
  • Spindle fibres attach to the kinetochores of each homologue
  • Nucleolus disappear and nuclear envelope have disintegrated
• Meiosis I (4. Metaphase I)

  • Tetrads: homologous pair of chromosomes align along the equator/ metaphase plate
  • Homologous pairs move to the metaphase plate with the help of the kinetochore microtubules
  • Each homologue is attached to the kinetochore microtubule from the pole it will be pulled towards in anaphase
  • Independent assortment occurs at this stage
  • Spindle is completely formed
  • attach to the centromere of each homologue)
  • Nucleolus -
  • Homologous pairs of chromosomes are held together at the CHIASMATA
  • Microtubules attach to the fused kinetochores of the sister chromatids
• Meiosis I (5. Anaphase I)

  • Homologous separate to opposite poles
  • Each homologue is pulled by a shortening kinetochore microtubule (that attaches to the centromere) towards one of the poles
  • ** Centromeres DO NOT divide here
  • Spindle fibres (non-kinetochore microtubules) elongate and slide in opposite direction due to the actions of motor proteins
  • Causes the 2 poles to move further apart
  • Nucleolus - 
  • Sister chromatids remain attached and move together towards the same pole (centromeres have not yet divided, this pair of sister chromatids is considered one chromosome)
• Meiosis I (6. Telophase I)

  • Cleavage furrow begins to form (i.e. cytokinesis begins at telophase I)
  • Spindle fibres disintegrate
  • Nucleolus reforms and nuclear envelope starts to reform around each group of chromosomes
  • Chromosomes each consisting of 2 sister chromatids reach opposite poles
  • Each pole has a haploid set of chromosomes (n)
  • Chromosomes sometimes decondense into chromatin but NO replication of DNA takes place
• Meiosis II (7. Prophase II)

  • Chromatin condense (forms shorter, thicker chromosomes)
  • Spindle fibres begin to form
  • Centrioles start to move to opposite poles
  • Nuclear membrane disintegrates, nucleolus disappears
• Meiosis II (8. Metaphase II)

  • Centromere of each chromosome is attached to kinetochore microtubules
  • Spindle is completely formed
  • Kinetochore microtubules align the chromosomes at the metaphase plate in a single file
  • Metaphase plate 2 is PERPENDICULAR to Metaphase plate 1
  • Sister chromatids are held together at the centromere
  • Microtubules attach to the individual kinetochores of the sister chromatids