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Mitosis & Meiosis (Ploidy - the number of sets of chromosomes in a…
Mitosis & Meiosis
- Cell division is fundamental for the growth and propagation of all living organisms
- Somatic cell division = MITOSIS
- Germinal cell division = MEIOSIS
- Mitosis = 2 identical daughter cells
= Meiosis = haploid gametes and opportunity for genetic recombination
Genome
- Organisms complete set of DNA, including all of its genes
- Each genome contains all of the information needed to build and maintain that organism
Metaphase
- Stage of cell division when chromosomes are aligned at the centre of the cell prior to separation
DNA packaging
- Nucleosome 147bp of DNA wrapped around a complex of 8 core histone molecules (normally 2 of each H2A, H2B, H3 and H4
- Variable length stretch of free DNA (8-114bp) separates adjacent nucleosomes.
- Stabilised by one molecule of the linker histone H1 - string of beads
- Histones = small highly basic proteins
- Carry a positive charge
- Give them affinity for negatively charged DNA
Chromosomal DNA is coiled hierarchically
- 30nm fibre corresponds to a linear condensation of the DNA molecule of about 50 fold of its stretched out length
- Further compaction to a 1000 fold in interphase and 10,000 fold in metaphase through complexing with non-histone proteins. Packaging details are not clear.
- DNA complexing with proteins forms a macromolecular complex called chromatin
Interphase
- Stage of cell cycle in between cell divisions
- Comprises of 3 phases G1 S & G2
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Chromosomes
- The fundamental units of eukaryotic genome organisation
- Faithful transmission and appropriate expression of genetic information
- Undergo major changes during the cell cycl
- Highly condensed in metaphase, gene expression is shut down
- In interphase chromatin extended to allow gene expression
- Structure in a cell on which genes are located consisting of a highly compacted stretch of DNA with associated proteins
Molecular structure of the centromere
- Specific region visible as a narrow constriction
- Serves as a central component of the kinetochore
- The complex DNA and proteins to which the spindle fibres attach to move chromosomes in meiosis and mitosis
- Tandem repeats of a family of related 170bp DNA sequences called alphoid DNA
Molecular structure of the telomere
- Each end of a linear chromosome is composed of a special DNA protein structure called a telomere
- Human telomere repeat TTAGGG
Mitosis
- Form of eukaryotic cell division that produces 2 daughter cells with the same genetic component as the parent cell
- Chromosomes replicated during the S phase are divided in such a way as to ensure that each daughter cell receives a copy of every chromosome
- Vital for tissue formatio and maintenance
- Mitotic cell division occurs in all embryonic tissues and continues at a lower rate in most adult tissues
- Cultured cells - duration of the cell cycle in 24 hours
-Mitosis itself occupies only 20 min to 1 hour of the total
Replication
- Mitosis is preceded by a process of DNA replication that converts each chromosome into 2 sister chromatids
The cell cycle
- Rapidly dividing cells have relatively constant interval between successive rounds of cell division
- After Mitosis (M) G1 (gap1) Transcription and Translation
- S-phase: When DNA replication occurs
G2 (gap 2) an interval during which the cell prepares for the M phase or Mitosis
Mitosis
- Prophase
- Metaphase
- Anaphase
- Telophase
Mitosis
- DNA replication has occurred furing interphase (in S phase) so at the start of mitosis the chromosomes consist of 2 long thin parallel DNA strands or chromatids held together at the primary constriction or centromere
Prophase
- Occupies over half of mitosis
- Chromosomes being to condense and the nuclear membrane breaks down
- Structure known as the centrosome duplicates itself to form 2 centrosomes that migrate to the opposite ends of the cell.
- Centrosomes organise the production of microtubules that for the spindle fibres that constitute the mitotic spindle
Metaphase
- The chromosomes are maximally compacted and they are lined up at the centre of the cell or equatorial plane.
- Spindle forms. Spindle fibres extend from the centrioles at the 2 poles of the mitotic figure, connecting to the protein complex known as the kinetochore located at the centromere
Anaphase
- The shortest stage of mitosis
- Disruption of the cohesin protein complexes holding sister chromatids tightly together at the centromere, releasing 2 independent chromatids
- Spindle fibre contract and draw the 2 sister chromatids (or daughter chromosomes) towards the poles of the cell (leading to even partitioning of the genetic material)
Telophase
- Mitosis is completed at Telophase with the formation of 2 new nuclear membranes and daughter cells separate by a process of cytokinesis. Spindle fibre disappear. Chromosome start to unwind
- Karyokinesis - mitotic nuclear division
- Cytokinesis - cell cytoplasm cellular division
Mitosis results in 2 daughter cells, each with an identical genetic constitution
C value - the amount of DNA contained within a haploid nucleus (a gamete) or one half the amount in a diploid somatic cells of a eukaryotic organism
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Meiosis
- Cell division that produces haploid sex cells or gametes from diploid cells
- Contain single copy of each chromosome
- Contain 2 copies of each chromosomes
- DNA replication is followed by 2 successive nuclear cellular divisions (meiosis 1 and meiosis 2)
- Only one round of DNA replication
Gametogenesis
- Production of gametes - eggs cells from oocytes and sperm cells from spermatocytes
- Occurs only in the gonads - ovaries and testis
- Somatic diploid chromosomal complement is halved to the haploid number of a mature gamete in such a way to ensure that each gamete contain one member of each pair of chromosomes
- This reduction is achieved by meiotic cell division
- Uniqueness of each gamete is assured by random segregation of maternal and paternal homologues and by recombination during the prophase of the first meiotic reduction division
- Recomdination is exhcnage of DNA between paternal and maternal chromosomes
Process of Meiosis
- Begins in oocytes during foetal life
- Males begins for a particular spermatogonial cell sometime after puberty
- Like mitosis, meiosis is preceded by a round of DNA replication
- Chromosomes consisting of 2 chromatids
- 2 rounds of cell division occur during the process of meiosis
Meiosis I
- Separates the pairs of homologous chromosomes
- From diploid cells to haploid cells
Meiosis II
- Separates each chromosome into 2 chromatids
- Process similar to mitotic division
First Meiotic Division
- Reduction division
- Homologous chromosomes pair intimately and may undergo genetic recombination
- The paring of the chromosomes is precise and involves formation of a protein structure called the synaptonemal complex
- Close apposition is required for recombination
5 stages of Prophase
- Leptotene
- start with the first appearance of the chromosomes.
- Each chromosome consists of a pair of sister chromatids.
- Replication has occurred in S phase of pre-meiotic interphase
- Zygotene
- Homologous chromosomes pair to form bivalents.
- Bound closely together by the synaptonemal complex (repetitive DNA and proteins)
- Pairing starts at the telomeres and proceeds towards the centromere
- Pairing is called synapsis
- Pachytne
- Main stage of chromosomal thickening
- Each chromosome is now seen to consist of 2 chromatids
- Each bivalent is a tetrad of four strands
- Diplotene
- Bivalents start to separate
-The centromere remains intact
- 2 chromatids of each chromosome remain together
- During longitudinal separation 2 members of bivalent are seen to be in contact
- called chiasmata which mark the location of crossovers. Where they have exchanged material. 55 chiamata per male cell. 1 chiasma per chromosome arm. 50% more in female.
- Diakinesis
- Chromosomes coil more tightly and so stain more deeply
- Metaphase being when the nuclear membrane
disappears
- Chromosomes move to the equatorial plane
Second Meiotic Division
- Follows the first without interphase
- Resembles mitosis
- Centromeres now divide and sister chromatids migrate to opposite poles
Consequences of Meiosis
- Gametes contain only one representative of each homologous pair of chromosomes
- Random assortment of paternal and maternal homologues
- Crossing over ensures uniqueness by further increasing genetic variation
Independent Assortment
- 2-23 or 8,388,608 different possible combinations of chromosomes in the gametes of each parent
- There are 2-46 possible combination in the zygote
- Still further scope for variations provided by crossing over during meiosis
Meiosis generates genetic diversity through:
- Exchange of genetic material between homologous chromosomes during Meiosis I
- Random alignment of maternal and paternal chromosomes in Meiosis I
- Random alignment of the sister chromatids at Meiosis II
Aneuploidy
- Usually arises from the failure of paired chromosomes or sister chromatids to disjoin at anaphase
- May be due to delayed movement of a chromosome at anaphase
- Either of these mechanisms 2 cells are produced, one with an extra copy of a chromosome and one with missing copy of chromosome
Causes of meiotic non-disjunction
- Maternal age
- Maternal hypothyroidism
- After viral infection
- Family tendency
- Altered expression of proteins involved either in kinetochore microtubule attachment or in the spindle assembly checkpoint
Female meiosis in humans
- Primary oocytes enter meiosis I during foetal development but are then arrested at prophase until after the onset puberty
- After puberty one primary oocyte completes meiosis with each menstrual cycle