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Cell Signaling
Animal cells communicate by:
• Direct contact (gap junctions)
• Secreting local regulators (growth factors, neurotransmitters)
• Long distance (hormones)
3 Stages of Cell Signaling:
1. Reception: Detection of a signal molecule (ligand) coming from outside the cell
2. Transduction: Convert signal to a form that can bring about a cellular response
3. Response: Cellular response to the signal molecule
1. Reception
• Binding between signal molecule (ligand) + receptor is highly specific.
• Receptors found in:a) Intracellular receptors (cytoplasm, nucleus) hydrophobic or small Eg. testosterone or nitric oxide (NO)
b) Plasma membrane receptor• water-soluble ligands
Plasma Membrane Receptors
G-Protein Coupled Receptor (GPCR)
Tyrosine KinaseLigand-Gated Ion
Channels
7 transmembranesegments in membrane
Attaches (P) to tyrosine
Signal on receptor changes shape
G protein + GTP activates enzyme cell response
Activate multiplecellular responses
at once
Regulate flow of specific ions(Ca2+, Na+)
G-Protein-Coupled Receptor
Receptor Tyrosine Kinase
Ligand-Gated Ion Channel
2. Transduction
• Cascades of molecular interactions relay signals from receptors target molecules
• Protein kinase: enzyme that phosphorylates and activates proteins at next level
• Phosphorylation cascade: enhance and amplify signal
Second Messengers• small, nonprotein molecules/ions that can relay
signal inside cell– Eg. cyclic AMP (cAMP) and Ca2+
3. Response
• Regulate protein synthesis by turning on/off genes in nucleus (gene expression)
• Regulate activity of proteins in cytoplasm
Apoptosis = cell suicide
• Cell is dismantled and digested
• Triggered by signals that activate cascade of “suicide” proteins (caspase)
– Protect neighboring cells from damage
– Animal development & maintenance
Cell Cycle: life of a cell from its formation until it divides
Functions of Cell Division: Reproduction, Growth and Tissue Renewal
Genome = all of a cell’s genetic info (DNA)
Prokaryote: single, circular chromosome Eukaryote: more than one linear chromosomes
Eg. Human:46 chromosomes, mouse: 40, fruit fly: 8
Each chromosome must be duplicated before cell division
• Duplicated chromosome = 2 sister chromatids attached by a centromere
Somatic Cells Gametes• Body cells• diploid (2n): 2 of each
type of chromosome• Divide by mitosis
• Humans: 2n = 46
• Sex cells (sperm/egg)• Haploid (n): 1 of each
type of chromosome• Divide by meiosis
• Humans: n = 23
Phases of the Cell Cycle
Phases of the Cell Cycle• The mitotic phase alternates with interphase:
G1 S G2mitosis cytokinesis• Interphase (90% of cell cycle)
– G1 Phase: cell grows and carries out normal functions
– S Phase: duplicates chromosomes– G2 Phase: prepares for cell division
• M Phase (mitotic)– Mitosis: nucleus divides– Cytokinesis: cytoplasm divides
Mitosis: Prophase Prometaphase Metaphase
Anaphase Telophase
Mitosis
1. Prophase– Chromatin fibers condense and coil– Nucleoli disappear– Spindle (microtubules) begins to form– Centrosomes begin to move to opposite ends
2. Prometaphase– Nuclear envelope fragments– Microtubules invade nucleus– Kinetochores attach to microtubules
Prophase & Prometaphase
Mitotic spindle at metaphase
Kinetochore = proteins associated with DNA at centromere
3. Metaphase– Chromosomes line up on metaphase plate at
equator– Centrioles are at opposite poles (ends)
4. Anaphase (shortest phase)– Chromatids separate and pulled apart by motor
proteins toward opposite ends of cell– Chromatids are called chromosomes now– Cell elongates
Metaphase & Anaphase
5. Telophase– Nuclear membrane re-forms around chromosomes– Chromosomes less condensed
Cytokinesis– Cytoplasm of cell divided– Animal Cells: cleavage furrow– Plant Cells: cell plate forms
Cytokinesis in animal vs. plant cells
During anaphase• Chromosomes
walked to poles by motor proteins
• Kinetochore microtubules shorten at ends as they depolymerize
Bacterial cells divide by Binary Fission
Cell Cycle Control System• Checkpoint = control point where stop/go signals
regulate the cell cycle
Major Checkpoints1. G1 checkpoint (Most important!)
– “Go” completes whole cell cycle– “Stop” cell enters nondividing state (G0 Phase)
• Nerve, muscle cells stay at G0; liver cells called back from G0
2. G2 checkpoint3. M Phase checkpoint
– Anaphase does not begin unless chromatids are properly attached to spindle at metaphase plate
G1 Checkpoint
Internal Regulatory Molecules
1. Kinases (cyclin-dependent kinase, Cdk): protein enzyme controls cell cycle; active when connected to cyclin
2. Cyclins: proteins which attach to kinases (Cdk) to activate them; levels fluctuate in the cell cycle
3. MPF: maturation-promoting factor; specific Cdk which allows cells to pass G2 and go to M phase
External Regulatory Factors
Growth Factor: proteins released by other cells to stimulate cell division
Density-Dependent Inhibition: crowded cells normally stop dividing; cell-surface protein binds to adjoining cell to inhibit growth
Anchorage Dependence: cells must be attached to another cell or ECM to divide
External Regulatory Factors
Cancer Cells
Cancer: disorder in which cells lose the ability to control growth by not responding to regulation.
• multistep process of about 5-7 genetic changes (for a human) for a cell to transform
• loses anchorage dependency and density-dependency regulation
Normal Cells Cancer Cells
Tumors = mass of abnormal cells
• Benign tumor: lump of cells remain at original site
• Malignant tumor: invasive - impairs functions of 1+ organs (called cancer)
• Metastasis: cells separate from tumor and travel to other parts of body
Types of Reproduction
ASEXUAL
• Produces clones (genetically identical)
• Single parent
• Little variation in population - only through mutations
• Fast and energy efficient
• Eg. budding, binary fission
SEXUAL
• Meiosis produces gametes (sex cells)
• 2 parents: male/female
• Lots of variation/diversity
• Slower and energy consumptive
• Eg. humans, trees
Chromosomes• Somatic (body) cell: 2n = 46 chromosomes• Each pair of homologous chromosomes includes 1
chromosome from each parent• Autosomes: 22 pairs of chromosomes that do not
determine sex• Sex chromosomes: X and Y
• Females: XX• Males: XY
• Gametes (n=23): 22 autosomes + 1 sex chromosome• Egg: 22 + X• Sperm: 22 + X **or** 22 + Y
Homologous Chromosomes in a Somatic Cell
Karyotype: a picture of an organism’s complete set of
chromosomes
• Arranged from largest smallest pair
Life cycle: reproductive history of organism, from conception production of own offspring
• Fertilization and meiosis alternate in sexual life cycles
• Meiosis: cell division that reduces # of chromosomes (2n n), creates gametes
• Fertilization: combine gametes (sperm + egg)
– Fertilized egg = zygote (2n)
• Zygote divides by mitosis to make multicellular diploid organism
Human Life Cycle
Meiosis = reduction division Cells divide twice Result: 4 daughter cells,
each with half as many chromosomes as parent cell
Meiosis I (1st division)Interphase: chromosomes replicatedProphase I: Synapsis: homologous chromosomes pair up Tetrad = 4 sister chromatids Crossing over at the chiasmataMetaphase I: Tetrads line upAnaphase I: Pairs of homologous chromosomes separate (Sister chromatids still attached by centromere)Telophase I & Cytokinesis: Haploid set of chromosomes in each cell Each chromosome = 2 sister chromatids Some species: chromatin & nucleus reforms
Meiosis II (2nd division) = create gametes
Prophase II: No interphase No crossing over Spindle formsMetaphase II: Chromosomes line upAnaphase II: Sister chromatids separateTelophase II: 4 haploid cells Nuclei reappear Each daughter cell genetically unique
Events Unique to Meiosis I (not in mitosis)
1. Prophase I: Synapsis and crossing over
2. Metaphase I: pairs of homologous chromosomes line up on metaphase plate
3. Anaphase I: homologous pairs separate sister chromatids still attached at centromere
Sources of Genetic Variation:1. Crossing Over
– Exchange genetic material
– Recombinant chromosomes
Sources of Genetic Variation:2. Independent Assortment of Chromosomes
– Random orientation of homologous pairs in Metaphase I
Sources of Genetic Variation:3. Random Fertilization
– Any sperm + Any egg
– 8 million X 8 million = 64 trillion combinations!
Mitosis Meiosis
Both are divisions of cell nucleus
• Somatic cells
• 1 division
• 2 diploid daughter cells
• Clones
• From zygote to death
• Purpose: growth and repair
• No synapsis, crossing over
• Gametes
• 2 divisions
• 4 haploid daughter cells
• Genetically different-less than 1 in 8 million alike
• Females before birth follicles are formed. Mature ova released beginning puberty
• Purpose: Reproduction
MENDEL’S PRINCIPLES
1. Alternate version of genes (alleles) cause variations in inherited characteristics among offspring.
2. For each character, every organism inherits one allele from each parent.
3. If 2 alleles are different, the dominant allele will be fully expressed; the recessive allele will have no noticeable effect on offspring’s appearance.
4. Law of Segregation: the 2 alleles for each character separate during gamete formation.
• P (parental) generation = true breeding plants• F1 (first filial) generation = offspring • F2 (second filial) generation = F1 offspring
Alleles: alternate versions of a gene
7 characters in pea plants
Dominant vs. Recessive(expressed) or (hidden)
Law of Segregation
dominant (P), recessive (p)• homozygous = 2 same alleles (PP or pp)• heterozygous = 2 different alleles (Pp)
Phenotype: expressed physical traitsGenotype: genetic make-up
Testcross: determine if dominant trait is homozygous or heterozygous by crossing with
recessive (pp)
Law of Independent Assortment:Each pair of alleles segregates (separates) independently
during gamete formationEg. color is separate from shape
• Monohybrid cross: study 1 character– eg. flower color
• Dihybrid cross: study 2 characters– eg. flower color & seed shape
The laws of probability govern Mendelian inheritance
• Rule of Multiplication:– probability that 2+ independent events will occur
together in a specific combination multiply probabilities of each event
• Ex. 1: probability of throwing 2 sixes– 1/6 x 1/6 = 1/36
• Ex. 2: probability of having 5 boys in a row– ½ x ½ x ½ x ½ x ½ = 1/32
• Ex. 3: If cross AABbCc x AaBbCc, probability of offspring with AaBbcc is:– Answer: ½ x ½ x ¼ = 1/16
The laws of probability govern Mendelian inheritance
• Rule of Addition:– Probability that 2+ mutually exclusive events will
occur add together individual probabilities
• Ex. 1: chances of throwing a die that will land on 4 or 5?– 1/6 + 1/6 = 1/3
Extending Mendelian GeneticsThe relationship between genotype and phenotype is rarely simple
Complete Dominance: heterozygote and homozygote for dominant allele are indistinguishable• Eg. YY or Yy = yellow seed
Incomplete Dominance: F1
hybrids have appearance that is between that of 2 parents• Eg. red x white = pink flowers
Codominance: phenotype of both alleles is expressed• Eg. red hair x white hairs = roan horses
Multiple Alleles: gene has 2+ alleles• Eg. human ABO blood groups
• Alleles = IA, IB, i• IA,IB = Codominant
Blood Typing
Phenotype(Blood Group) Genotype(s)
Type A IAIA or IAi
Type B IBIB or IBi
Type AB IAIB
Type O ii
Blood Transfusions
• Blood transfusions must match blood type• Mixing of foreign blood clumping death
Pleiotropy: single gene has multiple phenotypic effects (Eg. sickle cell anemia)
Epistasis: one gene alters the phenotypic expression of another gene (eg. albinism - white fur color in mammals)
ee overrides the expression of all the B,b genotypes
Polygenic Inheritance: the effect of 2 or more genes acting upon a single phenotypic character (eg. skin color, height)
Nature and Nurture: both genetic and environmental factors influence phenotype
Hydrangea flowers vary in shade and intensity of color depending on acidity and aluminum content of the soil.
Mendelian Inheritance in Humans
Pedigree: diagram that shows the relationship between parents/offspring across 2+ generations
Woman = Man = Trait expressed:
Genetic Testing
May be used on a fetus to detect genetic disordersAmniocentesis: remove amniotic fluid around fetus to
culture for karyotypeChorionic villus sampling: insert narrow tube in cervix
to extract sample of placenta with fetal cells for karyotype
Sex-linked genes
• Sex-linked gene on X or Y• Females (XX), male (XY)
– Eggs = X, sperm = X or Y• Fathers pass X-linked genes to daughters, but not
sons• Males express recessive trait on the single X
(hemizygous)• Females can be affected or carrier
Transmission of sex-linked recessive traits
Sex-linked disorders: ColorblindnessDuchenne muscular dystrophyHemophilia
X-InactivationBarr body = inactive X chromosome; regulate gene dosage in females during embryonic development
• Cats: allele for fur color is on X
• Only female cats can be tortoiseshell or calico.
Human development• Y chromosome required for development of testes• Embryo gonads indifferent at 2 months• SRY gene: sex-determining region of Y• Codes for protein that regulates other genes
Genetic Recombination: production of offspring with new combo of genes from parents
• If offspring look like parents parental types• If different from parents recombinants
• If results do not follow Mendel’s Law of Independent Assortment, then the genes are probably linked
Linked genes: located on same chromosome and tend to be inherited together during cell division
Crossing over: explains why some linked genes get separated during meiosis
• the further apart 2 genes on same chromosome, the higher the probability of crossing over and the higher the recombination frequency
Calculating recombination frequency
Linkage Map: genetic map that is based on % of cross-over events
• 1 map unit = 1% recombination frequency• Express relative distances along chromosome• 50% recombination = far apart on same chromosome
or on 2 different chromosomes
Nondisjunction: chromosomes fail to separate properly in Meiosis I or Meiosis II
Nondisjunction
• Aneuploidy: incorrect # chromosomes
– Monosomy (1 copy) or Trisomy (3 copies)
• Polyploidy: 2+ complete sets of chromosomes; 3n or 4n
– Rare in animals, frequent in plants
A tetraploid mammal. Scientists think this species may have arisen when an ancestor doubled its chromosome # by errors in mitosis or meiosis.
Chromosomal Mutations
Chromosomal Mutations
Exceptions to Mendelian inheritance• Genomic imprinting: phenotypic effect of gene
depends on whether from M or F parent• Silence genes by adding methyl groups to DNA
(methylation)
Exceptions to Mendelian inheritance
• Some genes located in organelles– Mitochondria, chloroplasts,
plastids– Contain small circular DNA
• Mitochondria = maternal inheritance (eggs)
Variegated (striped or spotted) leaves result from mutations in pigment genes in plastids, which generally are inherited from
the maternal parent.