Mitosis: Cell Division

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Chapter 12: Mitosis

• Cell division is vital for the cell cycle, enabling reproduction, growth, tissue renewal, and repair
• The cell cycle involves:
  • DNA duplication and condensation to produce identical genetic information
  • Disappearance of the nuclear envelope
  • Formation of cytoskeleton spindles
  • Distribution of DNA to daughter cells
  • Cytokinesis (cell division)
  • Reformation of the nuclear envelope
• Cell cycle phases can be determined through light microscopy, fluorescent dye/radioactive DNA synthesis analysis, or cell population DNA content analysis
• Genomes are organized with DNA packaged into chromosomes
• Somatic cells are diploid (2n), receiving 1n chromosomes from each parent
• Eukaryotic cells have chromatin, a DNA complex with proteins
• Chromosomes contain long DNA molecules carrying hundreds to thousands of genes
• Each nucleus contains about two meters of DNA
• DNA organization compacts DNA, protects it from damage, and facilitates gene expression and replication control
• Duplicated chromosomes have two sister chromatids joined along their length after the S-phase
• Microtubules attach to the centromere to separate sister chromatids
• Separated sister chromatids in the M-phase become chromosomes again
• Mitotic division produces two identical daughter cells
• Prokaryotic cell cycle steps:
  • Chromosome replication starts, and one origin copy moves to the cell's other end
  • Replication continues, with one origin copy at each end
  • Replication is completed, and the plasma membrane grows inward
  • A new cell wall forms
  • Results in two daughter cells
• Cell cycle checkpoints include G1, G2, and M checkpoints
• At the G1-S checkpoint:
  • Checks for growth factor presence
  • Checks for a favorable environment
  • Checks for cell size
  • Checks for damaged DNA
• At the G2-M checkpoint:
  • Checks if all DNA is replicated
  • Checks for damaged DNA
  • Checks for cell size
• At the M-checkpoint:
  • Checks if all chromosomes align at the metaphase plate
• p53 is a tumor suppressor gene crucial at G1-arrest
• Sensor proteins activate when DNA is damaged
• p53 then activates target genes, leading to cell cycle arrest and DNA repair
• Cyclins regulate the cell cycle by binding to and activating cyclin-dependent kinases (Cdks)
• Different cyclins and Cdks function in different cell cycle phases
• Active Cdks initiate cyclin degradation
• External signals, like growth factors, regulate the cell cycle too
• Cell growth in dishes relies on anchorage and density, forming a single layer
• Cancer cells grow independently of density, resulting in proliferation
• Multicellular organisms must coordinate cell behavior
• Loss of control in critical processes can lead to cancer involving:
  • Signal transduction pathways
  • DNA replication/repair
  • Cell cycle regulation
  • Cell-cell contact
  • Apoptosis
• Cancer development is a multistep process requiring approximately six mutations including:
  • Growth factor mutations
  • Tumor suppressor (p53) mutations
  • Apoptosis mutations
  • DNA repair enzyme mutations
  • Telomerase mutations
  • Metastasis mutations
• Benign tumors differ from malignant tumors, because benign tumors do not metastasize
• Tumor suppressor genes restrain cell growth, preventing malignancy
• Loss of suppressor gene function can cause cancer
• The most common inactivated tumor suppressor genes encode p53 and pRB, BRCA1, PTEN, and MSH2
• (Proto)oncogenes promote loss of growth control, which can convert a cell to a malignant state, lead to genetic instability, prevent apoptosis and promote metastasis
• Gain of function in oncogenes causes cancer
• Hundreds of oncogenes code for different cancers classified as:
  • Growth factors or receptors like EGFR
  • Cytoplasmic protein kinases like Ras
    • About 20% of all cancers involve the Ras gene
    • The Gly12 example describes a substitution mutation of amino acid
  • Nuclear transcription factors such as myc
  • Products affecting apoptosis such as bcl-2
• Unicellular organisms use cell division for reproduction
• Multicellular organisms depend on cell division for development, growth, and repair
• A genome is genetic material partitioned among chromosomes
• Eukaryotic chromosomes consist of a DNA molecule with proteins, creating chromatin
• Chromatin states vary in condensation
• Animal gametes have one chromosome set, and somatic cells have two sets
• Cells replicate genetic material before dividing
• Chromosomes duplicate before cell division, consisting of identical sister chromatids connected by a centromere
• Chromatid separation results in chromosomes of daughter cells
• Eukaryotic cell division includes mitosis and cytokinesis
• Mitosis involves: prophase, prometaphase, metaphase, anaphase, and telophase/cytokinesis stages

Mitosis Stages

• Prophase:
  • Chromatin coils, condensing into chromosomes
  • Nucleoli disappear
  • Duplicated chromosomes show identical sister chromatids joined at centromeres
  • The mitotic spindle starts forming, and centrosomes move apart
• Prometaphase:
  • The nuclear envelope fragments, and microtubules invade the nuclear area
  • Chromosomes become more condensed
  • Kinetochores form at each chromatid's center
  • Some microtubules become kinetochore microtubules
• Metaphase:
  • Centrosomes reach opposite poles
  • Chromosomes align at the metaphase plate
  • Sister chromatid kinetochores attach to kinetochore microtubules from opposite poles
• Anaphase:
  • Sister chromatids of each pair separate, becoming independent chromosomes
  • Daughter chromosomes move to opposite cell ends as kinetochore microtubules shorten
  • Cell elongates
• Telophase and Cytokinesis:
  • Animal Cytokinesis via cleavage
  • Plant cells create a cell plate
  • Two daughter nuclei form with nuclear envelopes
  • Nucleoli reappear
  • Chromosomes become less condensed
  • Remaining spindle microtubules depolymerize to complete mitosis
• The mitotic spindle controls chromosome movement during mitosis, and is made of microtubules
• Animal cells' mitotic spindles originate from centrosomes, including spindle microtubules and asters
• Some spindle microtubules attach to chromosome kinetochores, moving chromosomes to the metaphase plate
• Motor proteins then move separated sister chromatids along kinetochore microtubules
• Cell elongation arises from motor proteins pushing nonkinetochore microtubules

Regulation and Processes

• During binary fission in bacteria:
  • Chromosomes replicate
  • Daughter chromosomes actively move apart
• Some bacterial binary fission proteins relate to eukaryotic actin and tubulin.
• The eukaryotic cell cycle is controlled by a molecular control system, where cytoplasmic signaling molecules regulate processes
• The cell cycle stops at checkpoints in G1, G2, and M until a specific signal occurs
• Internal and external signals control cell cycle checkpoints
• Most cells show density-dependent inhibition of cell division and anchorage dependence
• Cancer cells bypass cell cycle regulation and divide unchecked, thus forming tumors
• Cancerous tumors can invade nearby tissues and metastasize

Chapter 13: Meiosis

• Mitosis is a cycle, but meiosis is not
• Some single-celled eukaryotes and plants reproduce asexually and sexually
• Sexual reproduction creates genetic variety through:
  • Independent assortment in meiosis I
  • Random fertilization of an ovum by sperm
  • Crossing-over between homologous chromosomes
• However, crossing-over does not always results in new variations
• Mitosis involves parental diploid cells (2n) dividing into two identical daughter cells (haploid, n)

Chapter 13: Chromosomes and Inheritance

• Chromosomes condense during mitosis, differing in size, centromere location, and banding
• Karyotypes of somatic cells show homologous chromosome pairs and autosomes (X/Y)
• Altered chromosome numbers, like trisomy, impact health
• Examples: Down syndrome (trisomy 21) arise from large or gene-rich chromosomes, causing dosage problems
• Offspring inherit parents' chromosomes with genes at specific loci
• Asexual reproduction through mitosis produces identical offspring
• Sexual reproduction yields genetically diverse offspring from two parents
• Normal human somatic cells are diploid: 46 chromosomes, 2 sets of 23 chromosomes
• 22 pairs of homologs are autosomes, and one pair are sex chromosomes
• Ovaries and testes create haploid gametes via meiosis
• Gametes contain 23 chromosomes and unite during fertilization, forming a diploid zygote
• Meiosis involves meiosis I and II, which results in four haploid cells
• Meiosis I reduces chromosome sets from diploid to haploid
• Three events mark meiosis I:
  • Prophase I: Synapsis and crossing-over between homologous chromosomes forming chiasmata
  • Metaphase I: Chromosomes align as homologous pairs
  • Anaphase I: Homologs separate, but sister chromatids stay joined at the centromere
• Meiosis II separates sister chromatids
• Sister chromatid cohesion and crossing-over maintain homolog pairing through anaphase I
• Cohesins cleave during anaphase I, allowing homologs to separate, but cleave at centromeres during anaphase II, releasing sister chromatids
• Sexual reproduction creates genetic variation with independent assortment, crossing over, and random fertilization
• DNA breaks and rejoins in homologous pairs during crossing over
• Genetic variation enables evolution by natural selection
• Mutations are the original source of variation; recombination creates genetic diversity

Chapter 14: Mendelian Genetics

• Character: A heritable feature differing among individuals.
• Trait: An inherited variation (dominant or recessive).
• Allele: Alternative gene forms for trait variations.
• Dominant: Observed trait masking the recessive variant.
• Recessive: Trait masked by the dominant form.
• Genotype: Gene combination in an organism.
• Phenotype: Outward appearance of an organism.
• Heredity: Passing characters from parents to offspring.
• Heterozygous: Individual with two different alleles.
• Homozygous: Individual with two identical alleles.
• Test cross: Breeding a mystery individual with a homozygous recessive to find allele composition using a Punnett square
• Mendel's segregation law states alternative gene versions cause inherited character variation
• Individuals get one allele from each parent
• The dominant allele expresses when alleles differ
• Alleles segregate during gamete formation such that egg and pollen receive one copy of each allele
• Recessive alleles express only with recessive alleles from both parents
• A dominant trait appears if a dominant allele inherited from either parent
• The dominant type is not always the wild type
• Genes on different chromosomes have independently segregating pairs of alleles
• The multiplication rule states probability of two independent events occurring together
• Addition rule states probability of one of two events happening
• Complete dominance: One functional allele is enough for the full effect
• Incomplete dominance: Insufficient proteins/enzymes for full requirements
• Codominance: Alleles are equally powerful but not always present

Dominance and Recessive Relations

• Dominant and recessive traits depend on the phenotype level studied including:
  • Whole organism: trait is dominant or recessive
  • Molecular level: codominance occurs
  • Biochemical level: incomplete dominance
• Epistasis occurs when one gene masks another
• Pleiotropy occurs when one locus affects multiple unrelated traits
• Multifactorial characters involve genetic and environmental factors, like the soil pH determining hydrangea color

Genetic Disorders

• Family history helps identify inheritance and predict offspring traits
• Heterozygous individuals typically are carriers, while homozygous individuals typically are affected by disease
• Mendelian inheritance distinguishes five disorder categories:
  • Autosomal Recessive:
    • All children affected if both parents are homozygous
    • Heterozygotes (carriers) have a 25% affected child risk
    • Equal male/female numbers
    • Rare traits means most affected people have no offspring
  • Autosomal Dominant:
    • Heterozygotes and homozygotes show abnormalities
    • Affected individuals have one affected parent
    • Children of affected individuals have at least a 50% risk
    • Affected parents can have unaffected children
  • X-Linked Disorders:
    • X-linked dominant disorders:
      • All affected males have only affected daughters
      • Heterozygous affected females transfer the trait to half their children
    • X-linked recessive disorders:
      • More common in males than females
      • Affected males get the allele from their mother and thus pass it on to their daughters
  • Y-Linked Disorders:
  • Only males affected
  • Limited syndromes
  • Eg: mutation/loss of SRY gene
  • Mitochondrial Inheritance
  • Offspring inherit mother's mitochondrial genes
  • Thus, mitochondrial traits always pass from mother to offspring

Mendelian Concepts and Genetic Relations

• Gregor Mendel's work established key concepts:
  • Genes have alleles that segregate during, and thus each sperm/egg carries one allele
    • This explains 3:1 F2 phenotype ratio
    • Organisms inherit one allele from each parent
  • Allele pairs segregate independently
    • The resulted dihybrid crossing has the 9:3:3:1 ratio
• Mendelian inheritance has two probability laws:
  • Multiplication rule states probability of two events occurring together
  • Addition rule states probability of an event occurring in multiple ways
• Relationships among single gene alleles:
  • Complete dominance means the heterozygous phenotype is the homozygous dominant phenotype
  • Incomplete dominance means the heterozygous phenotype is intermediate
  • Codominance means the heterozygotes express both phenotypes
  • Multiple alleles creates >2alleles for some genes
  • Pleiotropy entails a gene affecting multiple traits
• Allele relationships for two+ genes:
  • Epistasis: phenotypic expression of one gene has an affect on the other, for example coat color
  • Polygenic inheritance: many genes affect one ex: skin tone

Inheritance and Multifactorial Traits

• Genotype expresses with influences to environmental characters and multifactorial influences
• Phenotypes reflect combined genotype and environmental elements
• Complex inheritance patterns show Mendel's laws apply
• Family pedigrees determine genotypes
• Genetic disorders are inherited recessive traits
• Affected people usually have two normal carrier parents
• Heterozygotes of sickle-cell alleles have low malaria attacks
• Lethal dom. alleles are not passed on because those w/ them typically die before having kids
• Human diseases are multifactorial and can combine genetic components and enviromental problems
• Genetic disorders can be determined or genetic disorders through amniocentesis and chorionic villus sampling

Linkage and Gene Structure

• Genes inherit together if on the same chromosome
  • Do not assort independently
• Unlinked genes: 50% recombination rate
  • Can be far apart on the same chromosome
• Recombination occurs often among genes that are relatively far apart
• Inheritance has chromosome # and structural alterations (inversion, deletion, imprinting)
• noncoding RNAs (IncRNAs):
  • Large RNA class
  • No ORF's
  • Involved in gene expression, architecture, topology, and transcription
  • Also have micropeptides and regulatory proteins
• Chromosome structure alterations:
  • Mutation
  • Caused by inversion, deletion, imprinting
• Extragenomic inheritance's:
  • Occurs on or contains organelle DNA
  • Can be HIV
  • Through eggs
  • Methylation, and is known as genomic imprinting, this allows phenotypic affects that depend on allele
• The chromosome theory claims genes are on chromosomes and behaviors account for Mendel's laws
• Sex is mostly in chromosomes via:
  • XY in humans
  • Other chromosome/gender systems in alligators, birds, and fishes
• Mammal's' sex chromosomes are linked at the X-chromosomes
• Females, one X-chromosomes is turned off and condenses into the Barr body
• Linked genes have inheritable traits because where they're located

Gene Variety and Replication

• The di-hybrid's test cross allows the offsprings types to exhibit properties unseen by parents
• Uncombined genes allow a recombination rate by 50% to form gametes
• Genetically connected strands are linked over non-sister elements during meiosis
• Recombination occurs <50%
• Gene order and relative distance is deducted by recombinant
• Allows construction of a linkage map, and recombinant determines gene location
• Aneuploidy relates to uncommon chromosome #, results from nondisjunction
• Results in abnormal trisomy/monosomy
• Extra sets of chromosomes are known as poliploidy
• Broken chromosomes structural change
  • Deletion
  • Duplication
  • Translocation (Translocation and deletion)
• The alterations causes syndrome/cancers
• Mammals have imprints/which relys on which allele, causes offspring to not know who parent is
• Organelle transfer follows maternal parent only
• Nervous degradation due to damaged mitochondrial genes
• DNA polymerase is transcription enzyme
  • Discovered by Arthur Komberg
  • 5'to 3' DNA only
  • Primer needed
  • Perfection does not exist
• The DNA and diversity causes lewontin's paradox
• Prokaryotes DNA starts an end point and opens bi-directional
• Eukaryotes copy via different forks
• Helicase replicates replication forks
• 5' End-binders template with DNA
• Topoisomerase is helixes strands
• All strands produce short RNA
• DNA polymere replicates new strands from primer and pre-DNA
• "Removes previous primer from replication"
• Joins old copies together
• Repairs

Gene fidelity

• Error avoidance
• Nuclotide selectivity
• Replication is very important
• No template and broken OH causes blocking issues
• The repetitive sequences are known as telomeres that protects strands

Nuclei Acids

• DNA is genetic material -Bacteria/Phages have DNA -Crick and Watson deduced double helix and structures. A/T
• Replication/repair -Semi-conservative is unbinding which allows new codes -In the forks
• Helicase separates strands -3' works 5'-3

Chapter 17: Gene Expression

• The central dogma includes transcription, translation, replication, and reverse transcription
• The processes occur slightly differently between prokaryotic and eukaryotic cells
• The genetic code is redundant (one amino acid can be coded by multiple codons) but it is not ambiguous (a codon codes only one amino acid)
• 64 Codons exist and consist of the start codon and 3 stops
• Transcription occurs by distinguishing three phases:
  • Initiation
  • Elongation
  • Termination
• RNA polymerase attaches and initiates transcription at a promoter and unwinds the DNA
• RNA nucleotides pair and bond with DNA
• Transcription ends after signals in both eukaryotes and prokaryotes
• Eukaryotes contain three different RNA polymerase' instead of prokariote's one
• Termination, Eukaryotes- polyA signal recruits cleavage that breaks pre-Mrna
• Differences between types of RNA structure;
  • Eukaryotes involve different regulatory frameworks known as upstream, frames, and downstream

Gene splicing and editing:

• RNA processing is splicing in eukaryotes
• Genes cause introns to splice while mRNA keep
• Gene alternative results in protein differences
• Correct starting point is needed for genetic code use
• Then, mRNA is eventually translated to form a protein
• ribosomes join codes, rRNA, and tRNAs
• Protein has multiple parts, the tRNA has active enzymes which is joined by tRNA-Synthesis
• proteins are shaped through little assistance

The gene

• Post-translational modification: Lipids and degradation.
• Mutations express protein
• The DNA causes chemical synthesis with UV and causes mutations to be seen
• Mis-sense is changed codes
• No-sense leads to stop
• Silence is short and changes to the code
• Some coding does not change the effect due to:
• Placement
• Same coding from before
• Same amnio
• Coding may not part as coding for mRNA

Chapter 23: Microevolution

• Evolutionary heritable Microevolution is change within generations
• Most genetic variation caused by environmental factors
• Natural, selection action by genetic code with exceptions We define with two catergories
• Variation has short changes from nutagens
• Reorders chromosomes
• Exchange alleles
• Genetic drift
• Bottleneck is when environment changes suddenly
• Founder effect migration cause decreased genetic state
• As drifting effects chances of long term survive is effected
• non-random selection mating
• Nature is the natural survival of specific chromosomes

DNA

• Summary: DNA is material
• experiments shows as evidence this happens due to semi-conservative and code binding