The Cellular Basis of Reproduction and Inheritance Chapter 8 The Cellular Basis of Reproduction and Inheritance

CONNECTIONS BETWEEN CELL DIVISION AND REPRODUCTION Organisms can reproduce sexually or asexually Reproduction Sexual reproduction : the reproduction process that involves the union of a sperm and an egg Asexual reproduction : the production of offsprings by a single parent without the participation of sperm and egg

8.1 Cell division plays many important roles in the lives of organisms Some organisms make exact copies of themselves, asexual reproduction

Other organisms make similar copies of themselves in a more complex process, sexual reproduction Adults Sperm Egg fertilization Zygote (fertilized egg) development Offspring

8.2 Cells arise only from preexisting cells All cells come from cells Cellular reproduction is called cell division Cell division allows an embryo to develop into an adult It also ensures the continuity of life from one generation to the next

8.3 Prokaryotes reproduce by binary fission Prokaryotic cells (bacteria, archaea) divide asexually These cells possess a single chromosome, containing genes The chromosome is replicated The cell then divides into two cells, a process called binary fission Prokaryotic chromosomes Figure 8.3B

Binary fission of a prokaryotic cell chromosome Plasma membrane Cell wall Duplication of chromosome and separation of copies Continued elongation of the cell and movement of copies Division into two daughter cells

Figure 11-8 STEPS IN BACTERIAL CELL DIVISION https://www.youtube.com/watch?v=7Lh-M-rX86Q 1. Chromosome is located mid- cell. 2. Chromosome replicates. 3. Chromosomes pull apart; ring of FtsZ protein forms. 4. FtsZ ring constricts. Membrane and cell wall infold. 5. Fission complete.

THE EUKARYOTIC CELL CYCLE AND MITOSIS Eukaryotic cells have multiple chromosomes, while prokaryotic cells have usually one chromosome A chromosome consists of one molecule of DNA and a number of proteins The eukaryotic chromosome consists of a linear DNA, while prokaryotic one consists of a circular DNA The number of chromosomes in a eukaryotic cell depends on the species

Chromatin Chromosome

Chromosomes contain a very long DNA molecule with thousands of genes Individual chromosomes are only visible during cell division They are packaged as chromatin

Before a cell starts dividing, the chromosomes are duplicated Sister chromatids This process produces sister chromatids Centromere Figure 8.4B

When the cell divides, the sister chromatids separate Two daughter cells are produced Each has a complete and identical set of chromosomes

Chromosomes DNA molecules Sister chromatids Chromosome duplication Figure 8.3B Chromosomes DNA molecules Sister chromatids Chromosome duplication Sister chromatids Centromere Chromosome distribution to the daughter cells

8.5 The cell cycle multiplies cells The cell cycle consists of two major phases: Interphase, where chromosomes duplicate and cell parts are made The mitotic phase, when cell division occurs

8.6 Cell division is a continuum of dynamic changes Eukaryotic cell division consists of two stages: Mitosis : one nucleus  two nuclei Cytokinesis : the cytoplasm is divided into two Mitosis Cytokinesis

Mitosis : the equal division of one nucleus into two genetically identical daughter nuclei Prophase Metaphase Anaphase Telophase Interphase (G1, S, G2 phases) Chromosomal DNA is present as a form of chromatin DNA duplication in S-phase

Prophase Chromatin  chromosome structure Nucleoli disappear The nuclear envelope disappears Formation of the mitotic spindle Spindle microtubules attach to the kinetochores of chromosomes compaction At the centromere region, each sister chromatid has a protein structure called a “kinetochore”

MITOSIS INTERPHASE Prophase Prometaphase Centrosomes (with centriole pairs) Early mitotic spindle Fragments of the nuclear envelope Centrosome Chromatin Centrioles Kinetochore Nuclear envelope Plasma membrane Centromere Chromosome, consisting of two sister chromatids Spindle microtubules

Metaphase Arrangement of the chromosomes on the metaphase plate Anaphase Separation of the sister chromatids toward the poles Telophase Daughter nuclei reappear Chromosome  chromatin Nucleoli reappear Mitotic spindles disappear Cytokinesis와 telophase는 동시에 진행

MITOSIS Metaphase Anaphase Telophase and Cytokinesis Metaphase plate Cleavage furrow Mitotic spindle Nuclear envelope forming Daughter chromosomes

Microtubules – Tubulin subunits Fibers containing motor proteins + + Chromosome movement Kinetochore plates Chromosome

8.7 Cytokinesis differs for plant and animal cells In animals, cytokinesis occurs by cleavage This process pinches the cell apart Cleavage furrow Cleavage furrow SEM 140 Cytokinesis occurs with telophase, although it may actually begin in late anaphase Cleavage furrow Contracting ring of microfilaments Daughter cells Figure 8.7A

In plants, a membranous cell plate splits the cell in two Cytokinesis New cell wall Cell wall of the parent cell Cell wall Plasma membrane Daughter nucleus Vesicles containing cell wall material Cell plate Daughter cells Cell plate forming

Most animal cells divide only when stimulated, and others not at all 8.8 Anchorage, cell density, and chemical growth factors affect cell division Most animal cells divide only when stimulated, and others not at all In laboratory cultures, most normal cells divide only when attached to a surface They are anchorage dependent Most animal cells are normally anchored to an extracellular matrix or to other cells of the same tissue

Cells continue dividing until they touch one another This is called density-dependent inhibition Figure 8.8A

Cultured cells suspended in liquid The addition of growth factor

Anchorage Single layer of cells Removal of cells Restoration of single layer by cell division

8.9 Growth factors signal the cell cycle control system Proteins within the cell control the cell cycle Signals affecting critical checkpoints determine whether the cell will go through a complete cycle and divide Most important, in the middle of G1 G1 checkpoint Control system At the boundary of meta- and anaphase (at the G2-M boundary) M checkpoint G2 checkpoint https://www.youtube.com/watch?v=JcZQkmooyPk

G2 checkpoint Metaphase checkpoint Pass this checkpoint if: • chromosome replication is successfully completed • no DNA damage • activated MPF present Pass this checkpoint if: • all chromosomes are attached to mitotic spindle M Mitosis G2 Second gap First gap G1 DNA synthesis G0 S Mature cells do not pass this checkpoint (they enter G0 state) G1 checkpoint Pass this checkpoint if: • nutrients are sufficient • growth factors (signals from other cells) are present • cell size is adequate • DNA is undamaged

Cyclin-dependent kinase Cyclin concentration regulates MPF concentration. G1 S G2 M phase G1 S G2 M phase G1 S MPF activated by dephosphorylation of MPF Cdk MPF activated by dephosphorylation of MPF Cdk P P MPF component concentration MPF Cdk Cdk2 Cyclin A MPF Cyclin Time Activated MPF has an array of effects. Cdk Cyclin-dependent kinase Phosphorylate chromosomal proteins; initiate M phase Activated MPF P Phosphorylate nuclear lamins; initiate nuclear envelope breakdown Cyclin Cdk Phosphorylate microtubule- associated proteins. Activate mitotic spindle? Cyclin + Cdk with dephosphorylated, cyclin-dependent kinase subunit P Phosphorylate an enzyme that degrades cyclin; cyclin concentrations decline

The binding of growth factors to specific receptors on the plasma membrane is usually necessary for cell division Figure 8.8B Receptor protein Signal transduction pathway Growth factor Relay proteins Plasma membrane EXTRACELLULAR FLUID CYTOPLASM G1 checkpoint S M G2 Control system

Growth factors stimulate cell cycling e.g., Cells in your skin (arrested at G1 checkpoint) When you got a cut in the skin Platelets release platelet-derived growth factor Cell division of skin cells at wound

Cancer cells have abnormal cell cycle control systems 8.10 Connection: Growing out of control, cancer cells produce malignant tumors Cancer cells have abnormal cell cycle control systems They divide excessively and can form abnormal masses called tumors Radiation and chemotherapy are effective as cancer treatments because they interfere with cell division

Metastasis (전이): the spread of cells beyond their original site Lymph vessels Blood vessel Tumor Tumor in another part of the body Glandular tissue Growth Invasion Metastasis

Tumor : an abnormal mass of cells Benign tumor : an abnormal mass of normal cells Malignant tumor : an abnormal mass of cancer cells Classification of cancers Carcinoma : cancers derived from epithelial cells. E.g., skin cancer, cancers in lung, stomach, and other organs Sarcoma : cancers arising from connective tissue (bone, muscle, cartilage, fat, nerve) Lymphoma and leukemia : cancer arising from hematopoietic cells Blastoma : cancers derived from immature precursor cells Germ cell tumor

Cell cycle control system Function correctly Malfunction Normal cell Cancer cell Cell cycle control system Function correctly Malfunction Metastasis no yes Density-dependent inhibition of cell division Anchorage dependence of cell division The number of cell division definitely indefinitely

8.11 Review of the functions of mitosis: Growth, cell replacement, and asexual reproduction When the cell cycle operates normally, mitotic cell division functions in: Growth (seen here in an onion root)

Cell replacement (seen here in skin) Dead cells Epidermis, the outer layer of the skin Dividing cells Dermis Figure 8.11B

Asexual reproduction (seen here in a hydra) Offspring  clone of its parent Clones : genetically same organisms

Cell Somatic cell (body cell) – diploid cell Gamete (reproductive cell) – haploid cell

8.12 Chromosomes are matched in homologous pairs MEIOSIS AND CROSSING OVER 8.12 Chromosomes are matched in homologous pairs Somatic cells of each species contain a specific number of chromosomes Human cells have 46, making up 23 pairs of homologous chromosomes Pair of homologous chromosomes Locus Centromere Sister chromatids One duplicated chromosome

8.13 Gametes have a single set of chromosomes Cells with two sets of chromosomes are said to be diploid Gametes are haploid, with only one set of chromosomes e.g., Human diploid cell의 chromosome No. 2n (diploid number) = 46 Human haploid cell의 chromosome No. n (haploid number) = 23

Chromosome Autosome Sex chromosome : XX female, XY male in mammals e.g., 44 autosomes and 2 sex chromosomes in humans

At fertilization, a sperm fuses with an egg, forming a diploid zygote The Human life cycle At fertilization, a sperm fuses with an egg, forming a diploid zygote Repeated mitotic divisions lead to the development of a mature adult The adult makes haploid gametes by meiosis Meiosis : the chromosome number is reduced to half (2nn) Occur only in the reproductive organs (ovary, testis)

The human life cycle Haploid gametes (n  23) n Egg cell n Sperm cell Meiosis Fertilization Ovary Testis Diploid zygote (2n  46) 2n Key Mitosis Haploid stage (n) Multicellular diploid adults (2n  46) Figure 8.13 Diploid stage (2n)

8.14 Meiosis reduces the chromosome number from diploid to haploid 1 Diploid cell (2n) 4 Haploid cells (n) Interphase (S)meiosis Imeiosis II n Mitosis 1 Diploid cell (2n) 2 Diploid cells (2n)

Meiosis I Prophase I Over 90% of the time required for meiotic cell division Chromatin  chromosome Synapsis occurs : formation of a tetrad consisting of a homologous chromosome pair  homologous recombination (crossing over) occurs. e.g., 23 tetrads in human cells The nucleoli and nuclear envelope disappear Formation of mitotic spindle Attachment of spindle microtubules to tetrads

MEIOSIS I: Homologous chromosomes separate INTERPHASE: Chromosomes duplicate Prophase I Metaphase I Anaphase I Centrosomes (with centriole pairs) Spindle microtubules attached to a kinetochore Sister chromatids remain attached Sites of crossing over Centrioles Spindle Tetrad Chromatin Sister chromatids Nuclear envelope Centromere (with a kinetochore) Metaphase plate Fragments of the nuclear envelope Homologous chromosomes separate

2. Metaphase I Alignment of the chromosome tetrads on the metaphase plate 3. Anaphase I Separation (split-up) of tetrads toward the opposite poles 4. Telophase I and cytokinesis Reversal of prophase I

Meiosis II is essentially the same as mitosis The sister chromatids of each chromosome separate The result is four haploid daughter cells

MEIOSIS II: Sister chromatids separate Telophase II and Cytokinesis Telophase I and Cytokinesis Prophase II Metaphase II Anaphase II Cleavage furrow Sister chromatids separate Haploid daughter cells forming Figure 8.14, part 2

8.15 Review: A comparison of mitosis and meiosis For both processes, chromosomes replicate only once, during interphase Mitosis Meiosis Function Growth Cell replacement Asexual reproduction Production of haploid cells Nuclear division Once : 1 diploid cell  2 diploid cells Two times : 1 diploid cell  4 haploid cells Genetic recombination no yes Daughter cells Genetically same Genetically different

(before chromosome duplication) MITOSIS MEIOSIS I Parent cell (before chromosome duplication) Prophase Site of crossing over Prophase I Duplicated chromosome (two sister chromatids) Tetrad formed by synapsis of homologous chromosomes Chromosome duplication Chromosome duplication 2n  4 Metaphase Metaphase I Chromosomes align at the metaphase plate Tetrads (homologous pairs) align at the metaphase plate Anaphase Telophase Anaphase I Telophase I Homologous chromosomes separate during anaphase I; sister chromatids remain together Sister chromatids separate during anaphase Daughter cells of meiosis I Haploid n  2 MEIOSIS II 2n 2n No further chromosomal duplication; sister chromatids separate during anaphase II Daughter cells of mitosis n n n n Daughter cells of meiosis II

8.16 The mechanisms for production of offspring with genetic diversity from the same parent Independent orientation of chromosome tetrads at metaphase I of meiosis : n개의 homologous chromosome pair를 가지는 organism은 2n종류의 genetically different gamete를 형성 Random fertilization : n 종류의 sperm과 n 종류의 egg가 만나면 n2 종류의 zygote형성 Homologous (genetic) recombination at prophase I of meiosis Mutations

Two equally probable arrangements of chromosomes at metaphase I POSSIBILITY 1 POSSIBILITY 2 Two equally probable arrangements of chromosomes at metaphase I Metaphase II Gametes Combination 1 Combination 2 Combination 3 Combination 4 Figure 8.16

8.17 Homologous chromosomes carry different versions of genes The differences between homologous chromosomes are based on the fact that they can carry different versions of a gene at corresponding loci Alleles : different versions of a gene

duplicated chromosomes) Coat-color genes Eye-color genes C E Brown Black Brown coat (C); black eyes (E) C E C E Meiosis c e c e c e White Pink Tetrad in parent cell (homologous pair of duplicated chromosomes) Chromosomes of the four gametes White coat (c); pink eyes (e)

8.18 Crossing over further increases genetic variability Crossing over is the exchange of corresponding segments between two homologous chromosomes Genetic recombination results from crossing over during prophase I of meiosis This increases variation further

Chiasma Tetrad Figure 8.18A

How crossing over leads to genetic recombination Coat-color genes Eye-color genes How crossing over leads to genetic recombination Tetrad (homologous pair of chromosomes in synapsis) 1 Breakage of homologous chromatids Chiasma : the site on a tetrad where crossing over occurs Multiple crossovers can occur in each tetrad 2 Joining of homologous chromatids Chiasma Separation of homologous chromosomes at anaphase I 3 Separation of chromatids at anaphase II and completion of meiosis 4 Parental type of chromosome Recombinant chromosome Recombinant chromosome Parental type of chromosome Figure 8.18B Gametes of four genetic types

ALTERATIONS OF CHROMOSOME NUMBER AND STRUCTURE 8.19 A karyotype is a photographic inventory of an individual’s chromosomes Karyotype: the number and appearance of chromosomes in the nucleus of an eukaryotic cell Karyotyping is performed using lymphocytes arrested at metaphase A karyotype usually shows 22 pairs of autosomes and one pair of sex chromosomes

Giemsa Karyogram Hypotonic Fixative Packed red and solution white blood cells Fixative Giemsa White blood cells Stain Centrifuge Blood culture Fluid Centromere Sister chromatids Pair of homologous chromosomes 2,600 Karyogram

8.20 Connection: An extra copy of chromosome 21 causes Down syndrome This karyotype shows three number 21 chromosomes  trisomy 21 An extra copy of chromosome 21 causes Down syndrome (47 chromosomes)

The chance of having a Down syndrome child goes up with maternal age Figure 8.20C

8.21 Accidents during meiosis can alter chromosome number Abnormal chromosome count is a result of nondisjunction Either homologous pairs fail to separate during meiosis I Nondisjunction in meiosis I Normal meiosis II Gametes n + 1 n + 1 n – 1 n – 1 Number of chromosomes

Or sister chromatids fail to separate during meiosis II Normal meiosis I Nondisjunction in meiosis II Gametes n + 1 n – 1 n n Number of chromosomes Figure 8.21B

Fertilization after nondisjunction in the mother results in a zygote with an extra chromosome Egg cell n + 1 Zygote 2n + 1 Sperm cell n (normal) Figure 8.21C

8.23 Connection: Alterations of chromosome structure can cause birth defects and cancer Chromosome breakage can lead to rearrangements that can produce genetic disorders or cancer Four types of rearrangement are deletion, duplication, inversion, and translocation

Deletion Inversion Duplication Reciprocal translocation Homologous chromosomes Nonhomologous chromosomes

Cell death Necrosis (괴사) Apoptosis (programmed cell death)