Cell Division 2022 Lecture Notes PDF

Royal College of Surgeons in Ireland Medical University of Bahrain Cell Division Salim Fredericks Objectives 1. Define the phases of the cell cycle 2. List the stages and explain the mechanism and outcomes of mitosis 3. List the stages and explain the mechanism and outcomes of meiosis 4. E...

Royal College of Surgeons in Ireland Medical University of Bahrain Cell Division Salim Fredericks Objectives 1. Define the phases of the cell cycle 2. List the stages and explain the mechanism and outcomes of mitosis 3. List the stages and explain the mechanism and outcomes of meiosis 4. Explain the mechanisms producing genetic variation 5. Define basic terms in Mendelian genetics including: allele, genotype, phenotype, homozygote, heterozygote, dominant and recessive Cell Division Cell division required during development to generate new cells in the adult In somatic cells, division occurs by mitosis Mitosis occurs as part of the cell cycle diploid cells  diploid cells Meiosis is a specialized form of cell division giving rise to sperm and egg cells diploid cells haploid cells Cell cycle Phases of the cell cycle G2 (3-4 h) Mitosis (approx. 2 h ) A short Cell division resting phase before cell division occurs G0 (variable length) G0 is an optional non-replicative phase; many differentiated S (5-6 h) cells remain in G0, The ‘synthesis’ eg: hepatocytes phase - DNA replication occurs G1 (approx 10 h) A period of cell growth and preparation for cell division (incl. replication of key components, eg: centrosomes) Humans (2n) = 23 chromosome pairs, 22 autosomes + sex chromosomes Sex-determining chromosomes XX = female XY = male Mitosis Cell cycle: mitosis Mitosis is one sector of the cell cycle which describes how the genome goes from being – duplicated to – segregated Cell cycle: mitosis Genomic DNA must be copied accurately and divided between the daughter cells Mitosis: DNA is copied once; 46  92 chromosomes Cell divides once 92 chromosomes / 2 cells  46 chromosomes = 2 X 23 (diploid) Cell cycle : mitosis Concepts of Genetics 10th ed. W. Klug, et al., (2012) Cell cycle : mitosis Concepts of Genetics 10th ed. W. Klug, et al., (2012) Mitotic Spindle Centromere is essential for segregation during cell division. Chromosome fragments lacking centromere (acentric) do not become attached to spindle and are not passed to daughter cells Mitosis and DNA replication End result of DNA replication: two DNA molecules, each with one old strand and one new strand Both have the same sequence on each strand The two DNA molecules form the sister chromatids seen during mitosis they are separated during anaphase and each daughter cell gets one of them After separation, each chromatid is referred to as a chromosome  each daughter cell gets a full copy of the genetic information in the parent cell Meiosis  Meiosis reduces diploid to haploid Overview of meiosis Fate of two chromosome pairs rather than the true 23 pairs. The result of the two meiotic divisions (in this illustration and in reality) is four haploid cells. Meiosis: preceded by one round of DNA synthesis 5 stages of Prophase of Meiosis 1 Recombination: Exchange between maternal and paternal chromosome (homologs) Bivalent / Tetrad 4 stranded structure chromatids x 2 homologous chromosomes)  Bivalent align at Metaphase plate Spindle fibers pull one complete chromosome (2 Chromatids) to either Random segregation of paternal and maternal chromosomes pole = Independent assortment Division without replication Genetics From Genes to Genomes, 4th Edition Leland Hartwell, Leroy Hood, Michael Goldberg, Ann Reynolds, Lee Silver 2010 Egg formation begins in the fetal ovaries and arrests during the prophase of meiosis I. Fetal ovaries contain about 500,000 primary oocytes arrested in the diplotene of meiosis I. Only one of the three (rarely, four) cells produced by meiosis serves as the functional gamete, or ovum.  Genetics From Genes to Genomes, 4th Edition Leland Hartwell, Leroy Hood, Michael Goldberg, Ann Reynolds, Lee Silver 2010 Human sperm form continuously in the testes after puberty. Once they divide to produce the primary spermatocytes, the subsequent stages of spermatogenesis—meiotic divisions in the spermatocytes and maturation of spermatids into sperm Mitosis compared with meiosis Comparison of Mitosis and meiosis Genetics From Genes to Genomes, 4th Ed (2010) Hartwell, Hood, Goldberg, Reynolds, Silver Mechanism of variation  Genetic diversity is generated in Meiosis I by 2 processes: a) Independent assortment b) Recombination by crossing over For three pairs of homologs, eight (2 3 ) different alignments can occur. Our 23 chromosome pairs can line up in 8 million (2 23 ) different ways.  (1) Independent assortment Each bivalent is a 4-stranded structure (4 chromatids) The mitotic spindle pulls 2 chromatids towards each pole Which one? The choice maternal vs. Paternal homolog is random  223 = 8.4 x 106 possible combinations (2) Recombination Occurs during Pachytene in Meiosis I Physical breakage of the DNA duplex in one maternal and one paternal chromatid, and joining of the maternal & paternal ends DNA sequences are exchanged between the chromatids; but, DNA sequences are neither gained nor lost Unless a mistake : Non-disjunction Cytogenetics MM16 Recombination does not normally occur in mitosis; if/when it does, DNA sequences are gained or lost with bad consequences Meiotic tetrad with two chiasmata  Haploid (n) Diploid (2n) Haploid gametes arise by meiosis from diploid precursors Fertilisation: Sperm and egg chromosomes combine during the first mitosis forming diploid zygote. Further rounds of mitosis and differentiation to form the whole organism Basic terminology  Most cells are diploid: ie: two homologous copies of each chromosome [One maternal + one paternal] 2 copies of each gene, 1 per chromosome copy Each gene copy is called an allele Alleles can vary slightly in their DNA base sequence so an individual can have different alleles of a gene, eg: A & a In populations genes have many alleles; polymorphism Fundamentals of Anatomy & Physiology 4/e © Prentice Hall  Different alleles combine to produce different genotypes: AA or aa Homozygote Aa Heterozygote Genotype = genetic constitution Phenotype = physical appearance (healthy or disease) Phenotype is (largely) determined by genotype If A determines phenotype, it is said to be dominant a is therefore said to be recessive Simple Mendelian Inheritance [Single-genes] Recessive trait R = round vs. r = wrinkled in pea plants (R is dominant over r) Cross: Rr x Rr Progeny: Gametes: R & r R r R RR Rr Genotype ratio: 1 : 2 : 1 r Rr rr Phenotype: 3:1  Human inherited diseases Some diseases are caused by genetic (ie: DNA) defects disease genotype --- > disease phenotype Two broad categories: 1. Single-gene (monogenic) defects Single disease allele, dominant or recessive Simple Mendelian inheritance pattern 2. Multi-gene (polygenic) defects Interactions of several genes Complex (ie: non-Mendelian) inheritance  04_06.jpg Disease Expression?  Mendelian inheritance patterns: Autosomal dominant Autosomal recessive MM11 (Y - linked) MM12 MM 13 X - linked dominant X - linked recessive Identified in families by ‘Pedigree Analysis’ Further Resources: Chapter 2: Chromosome structure and function. Human Molecular Genetics, Strachan and Read. Mitosis http://www.biosolutions.info/2007/04/mitosis.html Meiosis http://www.biosolutions.info/2007/04/meiosis.html