Mitosis and Cell Division

Ch 12 - Mitosis Learning Outcomes

• Recognize key differences between unreplicated, replicated, and condensed chromosomes.
• Outline stages of cell cycle.
• List key steps of mitosis.
• Provide a comparison of cell division in bacteria, plant and animal cells.

Cell Division Overview

• Cell division produces new cells from existing cells.
• Eukaryote nuclei divide via Mitosis or Meiosis
• Mitosis produces somatic cells.
  • DNA is duplicated equally.
  • The daughter cells are genetically identical to their parent.
• Meiosis produces gametes.
  • Daughter cells get half the DNA amount.
  • Furthermore, daughter cells are genetically different.

Cellular Replication

• The basic steps of cellular replication are:
  • Copying DNA.
  • Separating the copies of DNA.
  • Cytoplasm divides leading to two complete cells (cytokinesis).

Chromosomes

• Chromosomes consist of a double helix of DNA wrapped around histones.
• Chromosomes contain multiple genes.

Cell Cycle Phases

• Phases include:
• M phase (mitotic or meiotic)
• Interphase (between phase)
  • S phase (DNA synthesis)
  • Gap phases:
    • G1 (cell growth, RNA and protein synthesis)
    • G2 (cell division preparation, organelle replication)
• Checkpoints in both gap phases make sure cell is ready

Mitosis Stages

• Prophase: Chromosomes condense, spindle apparatus forms
• Prometaphase: Nuclear envelope breaks, allows spindle attachment
• Metaphase: Chromosomes migrate to cell's middle
• Anaphase: Sister chromatids separate into daughter chromosomes
• Telophase: Nuclear envelope reforms, chromosomes de-condense

Prior to Mitosis

• During the G2 of interphase, chromosomes replicate into sister chromatids
• Centrosomes also replicate.

Prophase In Detail

• Chromosomes condense.
• Spindle apparatus begins to form.
  • The apparatus is composed of microtubules.
  • The apparatus provides mechanical force to move chromosomes and pull apart chromatids.

Prometaphase In Detail

• Nuclear envelope breaks down
• Microtubules contact chromosomes at kinetochores.
• Kinetochores are structures on each sister chromatid, assembled at the centromere.

Metaphase In Detail

• Chromosomes are lined up at the metaphase plate
• Astral microtubules interact with membrane proteins and hold spindles in place.

Anaphase In Detail

• Kinetochore microtubules shorten and pull sister chromatids apart.
• Anaphase ensures each daughter cell gets the same number and the type of chromosomes.

Telophase In Detail

• The nuclear envelope reforms, and the chromosomes decondense.

Chromosome Movement During Anaphase

• Microtubules shorten at the Kinetochore to pull daughter chromosomes apart

Cytokinesis

• Cytokinesis differs in plants and animals
• Plants: Microtubules direct vesicles to the cell center where they fuse.
• Animals: Actin-myosin interactions pinch the membrane.

Bacterial Cell Replication

• Bacterial cells replicate via binary fission.

Ch 13 - Meiosis Learning Outcomes

• Recognize differences between homologous chromosomes, sister chromatids, and nonsister chromatids.
• Describe stages of meiosis
• Compare and contrast meiosis I and II with mitosis.
• Determine amount of DNA and number of chromosomes at different meiosis stages.
• Explain how meiosis promotes genetic variation.

Meiosis

• Nuclear division halves the chromosome number via Meiosis.
• Gametes (reproductive cells) are produced.
• Fertilization maintains chromosome number.
  • Gamete + Gamete = Zygote
• Sexual reproduction allows for genetic diversity.

Chromosome Traits

• Every organism has a characteristic number of chromosomes that come in distinct sizes and shapes.
• Drosophila have 8 chromosomes arranged into 4 pairs.
• Sex chromosomes (X and Y) determine sex.
• All other chromosomes are called autosomes.

Chromosome Pairing

• Homologous chromosomes are the same size and shape.
• Homologous location contain the genes in the same location.
• However, homologs are not identical.
• Genes can have multiple alleles.
  • Those alleles can be different versions of the same gene.
• Codes for same trait with a slightly different DNA sequence, leading to slightly different trait expression

Concept of Ploidy

• Ploidy refers to the number of chromosome sets
• The variable n indicates the number of distinct chromosome types in a cell
• Haploid cells are "single form" (n) with one distinct chromosome type.
  • Bacteria, archaea, and fungi are examples.
• Diploid cells are "double form" (2n) with two homologs. -Drosophila and humans are examples.
• Polyploid cells have 3+ chromosome types (3n, 4n, etc).

Drosophila Chromosomes

• Drosophila has eight chromosomes
• It is diploid; It's ploidy is called diploid
• It has four sets; It's haploid number is "4"

Human Chromosomes

• Humans have 46 chromosomes; Its 2n is therefore equal to 46.

Life Cycle Ploidy Changes

• Meiosis reduces the number of chromosomes by half.
• Fertilization restores the diploid number of chromosomes.
• Life cycles vary among organisms.

Prior to Meiosis

• Chromosomes always replicate during the S-phase.

Meiosis

• Meiosis I and II separate homologous pairs and sister chromatids

Meiosis: Prophase I

• Synapsis: Homologous chromosome pairs bind together.
• Chiasmata: Physical connections form between chromatids.
• Crossing Over: Genetic material exchanges between nonsister chromatids.

Meiosis: Metaphase I

• Homologous pairs line up together at metaphase plate

Meiosis: Anaphase I

• Homologous pairs separate

Meiosis II

• Sister chromatids separate; Essentially mitosis but starts with half the chromosomes

Meiosis: Prophase I

• Crossing over can occur multiple times per one pair of chromosomes.

Genetic Variation in Meiosis

• Crossing over brings new allele combinations.
  • Genetic recombination occurs.
• Independent assortment during Meiosis I leads homologs to line up in different ways results in different daughter cell combinations.
• Fertilization, namely the union of two random gametes increases genetic variation.
  • Outcrossing involves gametes from different individuals combining to form offspring.
  • Self-fertilization involves two gametes from the same individual fusing to create a diploid offspring, and it is common in plants as opposed to animals that rely on hermaphrodites.

Genetics Gone Wrong

• Nondisjunction occurs when homologs, or sister chromatids, fail to separate
  • This leads to aneuploidy, or cells with an abnormal number of chromosomes.
• Viewing of the number and types of chromosomes present in an individual is done via karyotyping.

Mitosis versus Meiosis Summary

• Mitosis has one cell division; Meiosis has two.
• Chromosome number in daughter cells stays the same; Meiosis has half.
• DNA content in daughter cells goes down to 1/2 as chromosome counts shift from replicated to unreplicated.
• No Synapsis of homologs occur in mitosis, but it happens in Meiosis
• Spindle fiber attachment differs.
• Number of chiasmata is none.
• Makeup of chromosomes differs in daughter cells.
• The life cycle is for asexual reproduction in some eukaryotes.

Ch 12 Cell Cycle Regulation and Cancer Learning Outcomes

• Explain how cells regulate the progression of the cell cycle.
• Compare and contrast G1, G2, and M-phase checkpoints
• Explain how MPF controls progression of the cell cycle.
• Discuss how the G1 checkpoint failure can lead to cancer.
• Describe proto-oncogene function plus how a mutation of one will cause cancer.
• Describe tumor suppressor function plus how a mutation of one will lead to cancer.
• Indicate how the environment influences cancer genetics.
• Describe difficulty in curing cancer.

Cell Cycle Checkpoints (G1)

• The cell passes the G1 checkpoint if:
  • Cell size is adequate
  • Nutrients are sufficient
  • Social signals are present
  • DNA is undamaged
• Mature cells do not pass, they enter the G0 state instead

Cell Cycle Checkpoints (G2)

• The cell passes the G2 checkpoint if:
  • Chromosomes have replicated successfully
  • DNA is undamaged

Cell Cycle Checkpoints (M-phase)

• The cell passes the M-phase checkpoints if:
  • Chromosomes have attached to the spindle apparatus
  • Chromosomes have properly segregated

Cell Cycle Checkpoint Regulation

• Cyclins and cyclin-dependent kinases (Cdks) act together.
• Cyclins are different types for different phase transitions, like G1, G1/S, S and M. -Cyclins are produced when needed.
• Cdks are cyclin-dependent kinases that activate other proteins to progress the cell cycle when paired with a cyclin.

MPF (M-phase-promoting factor)

• Regulatory molecules control entry into the M phase
• Cytoplasm contains a regulatory molecule to induce M-phase in cells
• Cyclin B and Cdk1 are MPF

MPF

• Cyclin is the regulatory protein aspect of MPF
• Cdk is the Cyclin-dependent kinase for MPF

MPF Regulation

• Interphase: Cyclin B builds up and binds to Cdk, making Cdk inactive due to an inhibitory phosphate
• G2 checkpoint: Phosphatase removes the inhibitory phosphate, leading Cdk to activate
• M-phase checkpoint: Cyclin is degraded, inactivating Cdk1

G1 Checkpoint

• Checkpoint is controlled via:
  • Growth factors ("gas" of cell cycle)
  • Tumor suppressors ("brakes of cell cycle)
• G1 tumor suppressors:
  • p53 - DNA repair
  • Rb (pRB) - A block to G1 to S-phase transition

E2F

• E2F is the activator of S-phase
• Needs to be sequestered until cell is ready
• Cyclin E + Cdk2, leads to E2F release and cell cycle G1 to S progression

Cancer

• Too many growth factors, not enough phosphatases, too much E2F and mutated Rb can each defeat social control (and cause cancer)

Cancer Definition

• Cancer is several diseases caused by uncontrollable cell division that are invasive and spread to other sites in the body

Cancer Statistics

• The second leading cause of death in the US
• The number one cause of death for those aged 45-64
• 21% of deaths are from cancer
• Over 200 types exist

Types of Cancer

• Cancers are named by tissues in which they form, for example lung, or breast.
• It is described by the cell type that created it
  • Carcinoma from epithelial cells
  • Sarcoma from bone and soft tissues
  • Leukemia from bone marrow
  • Lymphoma from lymphocytes
  • Myeloma - plasma cells
  • Melanoma - melanocytes

Cancerous Traits

• Even one cell can begin to divide uncontrollably and form a tumor.
• Benign tumors are noninvasive and thus noncancerous.
• Malignant tumors are invasive and cancerous.
• Metastasis disperses it from a primary site into secondary sites.

Proto-oncogenes

• Proto-oncogenes promote cell growth and division (like growth factors).
• When mutated, proto-oncogenes become oncogenes and promote cancer development.
• Too much/ "broken" proto-oncogene = cancer.

Tumor Suppressors

• Tumor suppressors restrict cell growth and division
• Removal of these suppressors = cancer

Example: Growth Factors G proteins

• Growth factors (hormones that move cells through the G1 checkpoint)
• Example is Ras protein is active with or without growth facto.

Example: p53

• A cell cycle control and DNA repair protein
• If defective or missing, the inhibitory protein is absent, causing cancer.

Genetics of Cancer

• Cancer requires more than one malfunction
  • Tumor DNA typically has 2-8 mutations. 1+ oncogene and multiple tumor suppressors are typical.
• Genetic changes can be inherited; Predisposition increases likelihood based on person's makeup.
  • Often abnormal (mutant) copy of tumor suppressor
• Inheriting one mutant allele for either the p53 or BRCA1 genes increases likelihood.
• Environmental factors can cause it as well like Carcinogens.
  • Some carcinogenic substances are known by carcinogens.
  • Some exmaples include Tobacco, acetaldehyde, UV, outdoor pollution, coal tar.

Curing Cancer

• Curing cancer is difficult because it's not one disease, but many
• No singular cure possible and difficult to target cancerous cells
• New and rare cancers are appearing frequently
• Effective treatments include:
  • Surgery
  • Chemotherapy
  • Radiation
  • Targeted therapy
  • Immunotherapy.

Ch 14 - Genetics Learning Outcomes

• Describe the characteristics of models used in organisms
• Recall Mendel's theory of inheritance and identify how it differs from previous hypothesis.
• Correctly set up mono and dihybrid Punnett squares.
• Calculate genotypic and phenotypic ratios using Punnett squares.
• Compute offspring probabilities sans Punnett squares.
• Connect Mendel's principles to meiosis events.
• Discern sex-linked inheritance examples.
• Pinpoint resultant crosses of linked genes.
• Express relationship between the frequencies of linkage and recombination
• Complete a genetic map derived from one chart showing frequencies of recombination
• List and be able to recognize, instances of exceptions that depart beyond Mendelian-style inheritance.
• Include both multiple allelism with its accompanying codominance or cases of incomplete dominance when genes interact together along side epistasis that is accompanied by characteristics like quantitative traits where gene influences come into play etc
• Interpret pedigrees as mode/method for disorders

Gregor Mendel

• Mendel was the "Father of Modern Genetics".
• "Experiments over Plant Hybridization"
• Genetics is the branch of biology that focuses on trait inheritance.
• A trait can be any individual characteristic.

Hypothesis From Before Mendel

• Blending inheritance resulted with observed traits blend from mother and father leading then to offspring-based characteristics
  • In that scenario black sheep plus white variety will tend towards something which then gives its best prediction about black combined by use a of gray or white

Inheritance of Acquired Character

• Parents' traits change after a modification that also then moves through use onto future relatives, thus this then is "called acquired character Inheritance form"
  • If the Giraffe Extends necks via straining them and even further it can then yield a more sustained longer version for offspring variety

Peas as a Model Organism

• Practical to work via them; the conclusion applies to various and even otherwise new species
• The control of involvement for parents and so on requires mating for such individuals such as with self or cross-fertilization too
  • Two types that lead to mating include 'self-' vs and 'both- cross forms
• Having two or far beyond polymorphic type in a few ways or many; such characteristics lead towards the likes and shape for pods and /or seed, perhaps even there at last colors of same sorts

Experiments of Mendel

• Monohybrids, using a single trait
  • There were many pure lines which are also true breeding offspring.
  • Also, he had use of varied 'Hybrids', ones like he has often created whenever one had the trait but must make it, be, become a hybrid for just that quality then

Mendels Laws

• "Particulate Type of Interrelated factors"; Traits Are discrete + Never going away despite change from all these kinds traits / actions during their journey so much. Genes- A form for genetic determinant
• Alleles can then Be as traits if such alleles are now dominant enough
  • There at list- trait now becomes viewable in expression, where its 'dominant type is view as this at surface --- combination/genetic traits, as its geno as now
    • such, surface view that's apparent = phenotype and / where genetics lie = genetics

Genes, DNA and Chromosomes

• DNA is sequence based
• Genes lie at chromosomes

Principle of Segregation

• All alleles separate during gamete formation.
• Each gamete has only of each gene.

Mendel's Principles - Independent

• Alleles are separated from any other as opposed to sticking together as before

Rules for Punnett Squares

• First: Write separate gametes (make sure each cell has some distinct character) by the cells' unique gametes by parental origin
• Then: Make your squares that fits in whatever table by using column ratios to your best ability on how they compare there

Punnett Squares

• You have then calculated the genetic and surface factors to tell whether a offspring will appear in its final looks or rather will they harbor recessive properties and such

Dihybrid Crosses

• Breed via True type by breed that is RRYY along Side its other for wwyy , which the all will equal in short RrYy combination.

Drosophila

• Morgan showed that genes lie upon strands/chromosomes and linked evolution / heredity to those (in regards especially at ones via Darwinian evolution/ Darwin)
  • Easy, small with Abundant set at all as those come with few days

Drosophila Traits

• Type depends whether Wild i. E normal
  • Which it becomes that- a grayish/ Red and winged normal ones- or Mutant based on heritable (not there anymore if it is not for mutation, such is now the mutant, as it will become if it is for the latter vs some environmental change and in such that does not get pass for many)

Dihybrid Crosses

• The same outcome ratio of what appears after 4 has many cross and recombinated alleles through such way (4:3:3:1)

Sex Linked Inheritance

• To study cases it may help better understand male only version first if inheritance links into sex factors within a particular factor trait
• Y-Linked is gene linked to Y
• Sex chromosome may differ with set that makes them too, and they segregate during any making for those sperms if it does include

Genes Lying at Chromosome

• "With that it can be that when 2 such genes tend towards some form linkage among one such string , then"

Alleles - Always as Is

• The alleles are still heritable - It often differs with a sex based link somewhere - It appears if someone then also does the testing via offspring

Genetics Recombinants

ReCombinants: As if there's crossing of alleles so that we then create that final result via those from any recombinated or crossed factor.

Inheritance Pedigrees

• Can apply those principles even for inheritance, for example what we can come to see in humans by applying then various family traits

Modes of genetic Trasmission

• Carriers result because such way most recessives can stay within some individual that never had such gene that causes those problems but hold recessive allelic factors within its traits and offspring which then if given to both parents cause for both then cause affect