MEIOSIS

Features of Reproductive Systems

  • Humans are diploid (2n) and reproduce sexually by fertilization through the union of haploid (1n) gametes (sex cells)

    • Human diploid chromosome number: 46 chromosomes 

      • 22 pairs of homologous chromosomes 

        • 1 homolog from mother 

        • 1 homolog from father 

        • Homologs do not have exactly the same sequence 

      • 1 pair of sex chromosomes 

        • XX: Female

        • XY: Male 

    • Gametes are sperm and egg from male and female 

      • Haploid 

    • Fertilization results in fusion of gamete nuclei to form diploid zygote to give 22 pairs of chromosomes 

    • Zygote divides by mitosis to form (somatic) body cells and grow into the adult organism

  • Reproductive systems are blind-ended tubes with gametes produced at the proximal end and products released at the distal end 

    • Produced close to the body, sperm and egg

    • Excreted at the tip/outside

      • Gonads: proximal

      • Excurrent path: Between

      • Penis/Vagina: DIstal 

  • Reproductive organs are functionally homologous (same) for the male and female but structurally different 

    • Gonads are organs that produce gametes by meiosis 

      • Male: Testes 

      • Female: Ovary

    • Gonads produce and secrete sex hormones (steroids) made from cholesterol to facilitate gamete production and sexually dimorphic (same species different parts or looks) features 

      • Testis: Testosterone

      • Ovary: Estrogen and progesterone

    • Excurrent paths (ducts) for transport of gametes 

      • Male path: Epididymis→vas deferens→ejaculatory duct→urethra

      • Female path: Uterus→Vagina 

    • Glands for exocrine secretions that FACILITATE fertilization 

      • MALE: Seminal vesicle, prostate, bulbourethral (Cowper’s) glands

      • FEMALE: Uterus, bulbourethral (Bartholin’s) gland

    • Erectile Tissue involving blood hydrostatic pressure (ERECTION)

      • Male: Penis

      • Female: Clitoris 

  • Female reproductive system is specialized for nutrition of developing zygote and infant 

    • Uterus: Zygote to infant development via placenta

    • Mammary gland: Infant nutrition (BREAST FEEDING)


Meiosis 

  • eggs/sperm in prophase I


  • Mitosis and meiosis are processes that replicate cells 

    • Mitosis is cellular replication/duplication 

      • Mother cell divides to give two daughter cells with exactly the same genome

        • Daughter: Exactly the same DNA sequence as parent cell

    • Meiosis is reductive cell division 

      • Mother cell divides to give 4 daughter cells that have similar genomes 

        • Not exactly alike 

        • Gives genetic diversity to gametes 

        • Gametes have different combinations of genes on chromosomes compared to mother cell involving

          • Homologous recombination (crossing over) between homologous chromosomes during prophase I

          • Random segregation of maternal and paternal chromosomes during anaphase I 

PMAT→PP1M1A1T1

PRIOR TO MITOSIS: CELL CYCLE 

  • Cell cycle is involved in producing a large number of gametes 

    • Involves three major phases:

      • Interphase: when chromosomes are not visible by light microscopy but stuff is going on 

      • Karyokinesis: Packing up and separation of chromosomes

        • Splitting nucleus 

      • Cytokinesis: Splitting cytoplasm to give two daughter cells each containing a nucleus 

*Include checkpoints to see if there is enough growth factors to allow for cell division 

  • G1: Cell Growth of cytoplasm

  • S-Phase: DNA replication 

    • Make sister chromatid of chromosome 

    • Sisters get linked together

    • Sisters have the exact same DNA sequence

  • G2: Prepare for cell division (karyokinesis and cytokinesis)

  • Mitosis: PMAT

  • Cytokinesis


  • Gametogenic cells develop early in the embryo and can proliferate by mitosis prior to entering meiosis 

    •  Male: Proliferate after puberty and enter meiosis 

    • Female: proliferate during embryonic development, begin meiosis, arrest in meiosis 1 and complete meiosis after puberty

  • Gametogenic (-gonia) cells/germ cells: Diploid cells that produce gamates

    • Males: Spermatogonia

    • Females: Oogonia

  • Humans produce hundreds of thousands of trillions of gamates 

    • Females: Hundreds of thousands but functionally hundreds

      • Limited number released in lifetime 

    • Males: Trillions 

      • Produced whole life

Meiosis 

  • Prophase I

    • Chromosomes (sisters) compacted

    • Homologs pair up to form the tetrad 

      • Maternal sisters pair up with paternal sisters for each chromosome 

    • Crossing over: A sister of each homolog swap two or three regions of their chromosomes

      • Homologous recombination that unlinks genes on a chromosome 

      • Gives a unique combination of genes from the maternal and paternal homologs on the recombinant chromosomes

    • Chiasma: Regions where recombination occurred remain attached 

      • Separate during metaphase I

    • Very complex processes taking a lot of time hence the longest duration of meiosis 

      • Most female eggs are in this stage for 15-45 years 

  • Metaphase I 

    • Microtubules attach to each homolog at the centromere

      • Random attachment relative to aster later results in random segregation of maternal and paternal homologs for each chromosome 

    • Tetrads align at the midline of the cell, SPINDLE ATTACHES 

  • Anaphase I 

    • Homologs separated at the chiasma (NOT CENTROMERES) 

      • Separation of homologs reduces ploidy from diploid to haploid 

        • 2n→1n 

      • Future cell will either have the maternal or paternal version of each chromosome

      • 1x DNA and haploid chromosome number (46→23)

  • Telophase I

    • Homologs pulled to poles and reform nucleus 

  • Cytokinesis

    • Separates cytoplasm

INTERKINESIS: BETWEEN MEIOSIS I AND MEIOSIS II

  • Centrioles replicate but not DNA

Meiosis II

  • Involves karyokinesis and cytokinesis to produce two haploid cells with ½ the DNA and chromosomes

  • Prophase II

    • Condensation of chromatin to form visible chromosomes

  • Metaphase II

    • Microtubules attach to each sister of each chromosome 

    • Sisters for each chromosome line-up along the midline

    • Spindle attaches

  • Anaphase II

    • Sisters separated at the centromere 

  • Telophase II

    • Nuclei form at poles

  • Cytokinesis to separate the cells

Molecular Aspects about Meiosis 

  • Meiosis is a dorm of highly regulated double stranded DNA cleavage of one sister of one homolog followed by repair of using one sister of the other homolog

    • Double stranded DNA repair involves removing some of the DNA sequence at the cut site 

    • Need other homolog’s sequence to use for filling in 

  • Repair is followed by the separation of the Holliday junction and the axis of separation determines whether there is a crossing over event or a gene replacement 

    • Crossing over results in a recombinant chromosome where 1 part is from one homolog and the other from the other

      • Chromosome now has some maternal and some paternal genes

      • Of the four sisters, two are recombinant (mix of maternal and paternal chromosome regions), and two are not (just maternal or paternal)

  • Locations of crossing over have evolved such that they are same to give regions of the chromosome that remain intact 

    • Haplotype regions

    • Sites of cleavage are called recombination hot-spots 

  • Haplotype regions are used to determine ancestry and individual identification 

  • Recombination regions are in non-protein coding regions of the genome

  • Recombination does result in repair errors giving mutation in these regions 

  • Recombination sites and frequency used to determine proximity of genes 

    • Linkage analysis and linkage disequilibrium in pedigrees and populations

Hot where recombination, cold where low recombination 


Errors during Meiosis 

  • Errors result from failure to separate homologs during meiosis I or sister chromatids during meiosis II

    • Called nondisjunction errors: did not disjoin 

  • Most found in the population are sex chromosome aneuploidies with only am aneuploidy in chromosome 21 being compatible with life

    • Gene (chromosome) dosage in autosomes is important 

    • Under diagnosed because phenotypic effects are usually minor

  • Turner Syndrome

    • Only found with XO, females

  • Trisomy 21: Down’s Syndrome

  • XXXn: Trisomy or higher order X in females

    • Tall females

  • XXY: Klinefelter Syndrome 

    • High luteinizing hormone 

    • Cryptorchidism: Low testosterone due to testicles not descending

  • XYY: Jacobs Syndrome 

  • XX Mosaic: White spot in hair