Cell Reproduction: Mitosis & Meiosis Chapter 8 (and the beginning of Chapter 10)

Overview DNA replication Overview of cell division Mitosis Meiosis

DNA Replication Occurs during interphase of cell cycle 1 DNA molecule untwisted Each parent strand serves as template for new strand = 2 new DNA molecules, each ½ old & ½ new = semi-conservative replication

Enzymes break H bonds between 2 strands = unwinds & exposes nucleotide bases Free nucleotides pair with exposed bases Each parent strand has new one made on it = twist together to form double helix

DNA replication in a little more detail … Sugar-phosphate backbones of 2 DNA strands run in opposite directions 5’ end = Phosphate group on sugar’s C 3’ end = –OH group on sugar’s C

= 1 daughter strand synthesized continuously = Other daughter strand synthesized disjointedly DNA polymerase adds nucleotides to 3’ ends only Daughter strand grows in 5’ to 3’ direction

Replication Enzymes: Helicases Catalyze breaking of H bonds so double helix can unwind Work with small proteins to prevent rewinding of parent strands

Replication Enzymes: DNA Polymerases Catalyze addition of free nucleotides to exposed bases on each strand Also have proofreading abilities

Replication Enzymes: DNA Ligases Work on discontinuously-assembled strand Seal together short stretches of new nucleotides

Transcription vs. DNA replication Transcription Only part of DNA strand unwound RNA polymerase adds nucleotides to growing strand Results in 1 free mRNA strand DNA replication Whole DNA molecule unwound DNA polymerase adds nucleotides to growing strand Results in 2 double-helix DNA molecules

Mistakes occur that can be lethal if not caught e.g. wrong base-pairing DNA proofreading mechanisms fix most replication errors & breaks in strands (proofread & correct mismatches) Repair enzymes repair some changes by snipping out damaged sites or mismatches If mismatch can’t be fixed, replication is stopped

Cell Division: An Overview Parents reproduce to produce new generation of cells or multicellular organism Offspring inherits all information & metabolic machinery from parent

Prokaryotic cells reproduce asexually = binary fission Prokaryotic Cell Division

Eukaryotic Cell Division DNA in eukaryotic cells is in nucleus Eukaryotic cells can’t divide by fission Must copy & package DNA into > 1 nucleus before cytoplasm can split

Mitosis : –Produces 2 genetically identical cells –Happens throughout body Meiosis : –Produces 4 genetically different cells –Cells only have ½ of genetic info –Happens only in gonads Two Types of Cell Division

Mitosis One part of the cell cycle Growth, cell replacement, tissue repair Also used for asexual reproduction = organisms clone selves Unique to eukaryotes

The Cell Cycle The period from one cell division to next

Interphase: The Longest Phase 90% of cell cycle length

Interphase

G 1 : Gap / Growth Phase Cell growth # of cytoplasmic components doubled

S: Synthesis Phase DNA duplicated

Chromosome & copy = sister chromatids Joined at centromere

G 2 : Gap or Growth Phase II Makes proteins necessary for cell division Cell prepares to divide

Cells stay in G1 if making macromolecules Enter S when DNA & accessory proteins are copied Rate of DNA replication is same for all cells of a species

Same cycle length for same type of cells Different cycle lengths for different types of cells e.g. cells in red bone marrow divide every second e.g. nerve cells stay in G1 indefinitely Rate of cell division is under control (checkpoints, molecular brakes, etc.)

After G 2, cell enters mitosis Mitosis maintains cell’s chromosome #

Chromosome Number Humans have 46 chromosomes = diploid (2n) 2 of each type of chromosome = one set from mother, one from father

During mitosis: Each 2n parent cell produces two 2n daughter cells Each daughter cell has each pair of chromosomes = 23 pairs

During mitosis, 2 sister chromatids (duplicated chromosomes) separate Each becomes independent chromosome that ends up in 1 of daughter cells

The Mitotic Spindle Present in every cell Made of microtubules = change length by addition or removal of tubulin subunits Originates from pair of centrioles

Early in cell division, duplicated chromosome is condensed = coils up DNA winds twice around histones = nucleosome Keeps chromosomes organized during nuclear division

Late Interphase / Pre-Prophase Outside of nucleus, 2 centrioles duplicate selves

Early Prophase Inside nucleus: Chromosomes begin to condense Outside nucleus: Spindle begins to form Nuclear envelope begins to fall apart

Late Prophase Nuclear envelope completely falls apart Spindle fibres from each pole attach to sister chromatids of each chromosome

Metaphase Chromosomes line up halfway between spindle poles

Anaphase Sister chromatids of each chromosome separate & move to opposite poles (motor proteins attached to kinetochores drag chromatids along microtubules) Spindle poles pushed apart by growing microtubules

Telophase 1 of each type of chromosome reaches each spindle pole = 2 identical groups of chromosomes at each cell pole Chromosomes decondense Nuclear envelope forms around each cluster of chromosomes = two nuclei, each with 2n # of chromosomes

Cytokinesis Cytoplasm of cell divides Results in 2 daughter cells, each with same number of chromosomes as parent cell

Cytokinesis in Animal Cells Contractile ring mechanism Halfway between cell’s poles, plasma membrane constricts = cleavage furrow (ATP energy causes contraction of actin filaments) Cleavage furrow deepens until cytoplasm split into 2

Cytokinesis in Plant Cells Cell plate formation Golgi vesicles move to cell equator & fuse Vesicle membranes become cell membranes Contents become cellulose cell wall

Summary of Mitosis Nuclear & cellular division that maintains chromosome # Used for growth, repair, asexual reproduction

Cell division & DNA replication regulated so that: DNA only replicated once before cell division Cells that never divide do not replicate DNA Cells don’t try to replicate DNA if lack the energy & raw materials to complete process

Cellular Controls over Mitosis Anchorage dependence Animal cells must be in contact with a solid surface to divide Density-dependent inhibition Crowded cells stop dividing Growth factors Required to start & continue dividing Secreted by other cells

Cell Cycle Checkpoints Cell cycle has checkpoints: –Structure of chromosomal DNA monitored –Completion of phases monitored –Determines if good time for cell division Rely on internal & external cues

G 1 checkpoint is most important: If no go-ahead signal, cell will switch to non-dividing G 0 phase e.g. nerve & muscle cells remain in G 0 indefinitely

Cancer & Cell Division If immune system doesn’t recognize & destroy a cancerous cell, it may divide multiple times & form a tumor Benign Cells remain localized Malignant Spreads to other parts of body & disrupts function

Why don’t cancer cells follow the rules? Don’t exhibit density-dependence Have defective control systems Ignore / over-ride checkpoints Some synthesize own growth factors so continue dividing Divide indefinitely

Types of Cancers Carcinomas Internal & external coverings of body e.g. skin Sarcomas Supportive tissues e.g. bone & muscle Leukemias & Lymphomas Blood-forming tissues e.g. bone marrow, spleen, lymph nodes

Ways to Treat Cancer If not severe: Surgical removal of tumor Radiation therapy (damages DNA of cancer cells to greater degree than normal cells)

If severe: Chemotherapy Uses drugs to disrupt cell division e.g. Paclitaxel freezes the mitotic spindle at metaphase e.g. Vinblastin prevents spindle formation Also affects rapidly-dividing normal cells e.g. intestinal lining, immune cells, hair follicle cells

Cloning Donor cells from 1 animal starved so enter non-dividing G 0 phase Nucleus removed from unfertilized egg cell of another animal

Donor cell & egg cell placed next to each other in culture dish & electrically stimulated Cells fuse & enter mitosis

Cell continues mitotic divisions & forms embryo Embryo implanted into surrogate mother (same spp. as egg cell) Surrogate mother gives birth to genetic twin of “donor cell” animal

Mitosis: –Occurs in somatic cells –Results in 2 genetically identical cells –Growth, cell replacement, tissue repair = asexual reproduction Meiosis: –Occurs in sex cells –Results in 4 genetically different cells with ½ genetic info of parent cell = sexual reproduction Mitosis vs. Meiosis

Asexual vs. Sexual Reproduction Asexual reproduction: Individual makes multiple offspring with identical DNA Sexual reproduction: Allows for variety in heritable traits Adaptive in changing environments Meiosis → formation of gametes → fertilization

The Eukaryotic Chromosome Double-stranded DNA & associated proteins Chromosomes duplicated during interphase UnduplicatedDuplicated Centromere Sister chromatids

Chromosome Number Almost every cell in body has 2 complete sets of chromosomes One set from mother, one from father 2 sets = diploid (2n) Each cell has 2 versions of each gene

Homologous chromosomes Pair of chromosomes that carry genes for same heritable traits Except sex chromosomes (X or Y)

Genes Sequences of chromosomal DNA Contain heritable information to make new individuals Individuals have pairs of genes on pairs of chromosomes Each member of pair of gene = allele

Allele One of the variant forms of a gene at a particular (locus) location on a chromosome Different alleles produce variation in inherited characteristics (e.g. hair & eye colour, etc.) Basis for evolution: endless combinations of alleles lead to variations in traits

So What is Meiosis? Nuclear division that halves chromosome # Occurs only in sex (reproductive) cells 1 st step in formation of gametes ( or ) Gametes fuse with opposite sex gametes to form new individual

Humans are diploid (2n) with 46 chromosomes ( homologous chromosomes) Meiosis halves chromosome number so daughter cells (gametes) are haploid (n) with 23 chromosomes

Gametes Have only 1 set of chromosomes = haploid (n) Each gamete has 1 allele for each gene In humans = eggs or sperm

During meiosis, one cell goes through 2 divisions to end with formation of 4 cells, all with haploid (n) nuclei

Interphase Same as in mitosis: Cell grows & duplicates cytoplasmic components DNA is replicated

Prophase I Chromosomes condense Crossing-over occurs between homologous chromosomes Centrioles move to opposite sides of nuclear envelope Nuclear envelope begins to fall apart

Crossing Over When chromosomes condense during prophase, homologous chromosomes stick very closely together & form a tetrad

Maternal & paternal chromosomes swap genes = exchange segments of genetic info Homologous chromosomes become mixture of maternal & paternal info chiasma

Metaphase I Homologues of chromosomes tethered by microtubules at opposite spindle poles Chromosomes line up along equator of cell

Anaphase I Chromosomes pulled apart & move towards respective poles Poles move further apart

Telophase I Cytoplasm divides Results in 2 haploid cells (only have 1 of each pair of homologous chromosomes) Chromosomes still duplicated

Prophase II New mitotic spindle forms in each cell Chromatids of each chromosome become tethered to opposite poles

Metaphase II Chromosomes line up along equator of cell

Anaphase II Chromatids separate & move towards opposite poles Spindle poles pushed apart

Telophase II Nuclear envelope forms around each chromosome cluster

Cytokinesis Cytoplasm divides Results in 4 haploid (n) daughter cells Chromosomes are unduplicated

Meiosis—things to pay attention to: 1.DNA replication: a.Occurs only during interphase before Meiosis I 2.Meiosis I a.Prophase: crossing-over b.Metaphase: line up in 2 rows c.Anaphase: separation of homologous chromosomes 3.Meiosis II a.Similar to mitosis but no interphase precedes it b.Division results in haploid cells

Meiosis & Trait Variation Can occur via: –Crossing over –Random alignment of chromosomes at metaphase I

Exchanges of allele-containing segments occurs between non-sister chromatids (i.e. between maternal & paternal chromosomes) Gene-swapping: different versions of heritable information are swapped = leads to recombination of genes & variation in traits a. Crossing Over

b. Metaphase I Alignments a.k.a random assortment Duplicated chromosomes randomly tether to spindle poles i.e. no set rules for where maternal & paternal chromosomes should be positioned

Which half of homologous chromosome pair ends up at which pole is totally random 2 23 (8,388,608) possible combos of maternal & paternal chromosomes!

From Gametes to Offspring In animals, diploid germ cells become gametes Gametes differ from species to species

Male Gamete Formation Germ cell (spermatogonium) develops into 1° spermatocyte Enters meiosis Results in 4 haploid cells (spermatids) that differentiate into sperm cells

Female Gamete Formation Germ cell (oogonium) develops into 1° oocyte (immature egg) Grows in size 4 daughter cells differ in structure & function

When 1° oocyte divides after meiosis I, one daughter cell (2° oocyte) gets most of cytoplasm Other cell (1 st polar body) is very small

After meiosis II, one of 2° oocyte’s daughter cells is 2 nd polar body (also very small) Other gets most of cytoplasm and develops into ovum (egg) 1 st polar body’s daughter cells are both polar bodies

Polar bodies eventually degenerate Sole function: to ensure ovum is haploid Ovum gets most of cytoplasm & metabolic machinery Is able to support early cell divisions of new individual after fertilization

Fertilization: When 2 Gametes Become 1 Male & female gametes unite Haploid nuclei fuse Restores diploid nature of cells (n + n = 2n) ↑ variation among offspring: –Random gametes fusing –Millions of possible chromosome combos in each gamete

Summary of Meiosis Nuclear division that halves chromosome number Results in n male & female gametes that can fuse during fertilization to produce 2n offspring

Chromosomal Abnormalities Abnormal chromosome structure: Breakage of chromosome leads to rearrangements that affect genes on that chromosome Abnormal chromosome number: Chance events occur before or after cell division that result in wrong chromosome #

Changes in Chromosome Structure Can have neutral to harmful effects, depending on type of chromosomal change 4 types of rearrangement: Inversion Deletion Duplication Translocation

(a) Inversions Broken fragment reattaches to original chromosome but in reverse direction Genes still present in normal #, so less harmful than other categories

(b) Deletions Fragment of chromosome is lost Cause severe physical & mental problems e.g. cri du chat

(c) Duplications Fragment from one chromosome joins to a sister chromatid or homologous chromosome Can have severe effects

(d) Translocations Fragment of chromosome attaches to non-homologous chromosome May or may not be harmful

If chromosomal changes occur in sperm or egg cells: = may cause congenital disorders If chromosomal changes occur in somatic cells: = can lead to development of cancer (which is why cancer is generally not heritable)

Heritable Changes in Chromosome # Chance events occur before or after cell division that result in wrong chromosome # Consequences can be minor or lethal

Most changes in chromosome number occur because of non-disjunction = 1 pair of chromosomes do not separate during mitosis or meiosis

Aneuploidy: Normal #  1 chromosome e.g. trisomy 21 (Down Syndrome) Polyploidy: 3n, 4n, etc. Normal in many plants & animals

# of sex chromosomes can also be abnormal E.g. XO, XXX, XXY, XYY Will return to this when covering inheritance