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Flashcards in this deck (242)
  • The Common Receptors: - Ligand gated channels - G-Protein Coupled Receptors - Receptor Tyrosine Kinases - Steroid Hormone Receptors (Nuclear Receptors) - Misc. Other types - Protein Stability Signaling.

    biology signaling
  • Notch pathway

    • Signaling by Protease CleavageBoth fragments can pass a signal.

    notch signaling
  • Many caspases come together to signal a cell to undergo apoptosis (programmed cell death).

    biology apoptosis caspases
  • Multiple ways to start the cascade: Either from cells outside (immune cells) or from internal signals (nucleus or mitochondria).

    biology apoptosis signaling
  • In some cases, inhibition of proteolysis can lead to a signal being transduced.

    signaling wnt
  • wnt ligands bind to the heterodimeric receptor, and then recruit proteins that normal target beta-catenin for proteolysis.

    wnt receptor
  • If left intact beta-catenin can induce transcription of genes.

    wnt beta-catenin
  • Cell Signaling allows information from the outside of the cell to influence what is happening on the inside.

    cellsignaling biology
  • Steroid and gases can signal through membranes, although most signals are mediated by receptors in the plasma membrane.

    cellsignaling membranes
  • Signals can be passed through either proteins or lipids.

    cellsignaling molecules
  • Signaling is in many instances mediated by phosphorylation events of proteins. Phosphorylation can either activate or inhibit proteins.

    cellsignaling phosphorylation
  • Some signals are passed through the exchange of GDP to GTP and then the signal is completed following hydrolysis back to GDP.

    cellsignaling gtp
  • Rather that transducing the signal directly, G-protein coupled receptors utilize a second messenger to directly downstream changes, i.e. cAMP or CA2+.

    cellsignaling gpcr
  • Some signals can be passed by the cleavage of a pro protein to make an active signaling molecule.

    cellsignaling proteolysis
  • Signaling pathways do not function in isolation, but interact allowing for highly complex reactions.

    cellsignaling systems
    • Comic strip showing Homer Simpson doing his own business and Bart Simpson acting as a Kinase, transferring a phosphate from ATP to Homer, resulting in Homer being energized or altered.
    biology signaling kinase
  • Diagram: a cell receiving a signal from an external receptor, leading to a cascade involving the cytoskeleton, ER, and Golgi, and ultimately resulting in a cell signal to another cell.

    cell-signaling
  • The nucleus contains DNA, pre-mRNAs, and mRNAs, and shows the process of protein synthesis and translation.

    central-dogma gene-expression
  • Sequence shown in the diagram: - DNA of chromosome - pre-mRNAs - mRNAs - Protein

    central-dogma sequence
  • Gregor Johann Mendel

    mendel genetics
  • Planned to be a Monk and a teacher, but failed the teaching exam, so had to go back to school.

    biography mendel
    • Study Mathematics (Combination Theory)
    • Physics (With Doppler)
    • Paleontology
    • Biology (Scientific botany)
    study subjects
  • Studied Psium sativum (Garden Pea).

    pea mendel
  • Mendel Thought Different

    mendel genetics
  • Important methods Mendel used: - Good Record Keeping - Counted Everything - Create Theory and Make Predictions

    mendel methods experimental
  • Phenotype: The Physical manifestation of an organisms genetic make up.

    phenotype genetics
  • • Based on the cross to the right, what ratio of yellow to green peas would we expect in the F2 generation? • Why?

    Diagram showing a genetic cross of yellow peas (pollen) and green peas (eggs) as parents (P), resulting in all yellow peas in the first filial generation (F1), and a mix of yellow and green peas in the second filial generation (F2) after self-fertilization.

    Generation, Parental (P) (pure-breeding), Yellow peas (♂: pollen), Green peas (♀: eggs), First filial (F1), All yellow, Self-fertilization, Second filial (F2), 6022 yellow : 2001 green.

    genetics mendelian
  • What Mendel Found! Yellow Vs. Green

    mendel genetics
  • What Mendel Found! Round Vs. Wrinkled

    mendel genetics
  • Generation, Parental (P) (pure-breeding), Yellow peas (♂: pollen), Green peas (♀: eggs), First filial (F1), All yellow, Self-fertilization, Second filial (F2), 6022 yellow : 2001 green.

    mendel inheritance ratios
  • Diagram illustrating the segregation and inheritance of alleles in the F3 generation from self-fertilization of F2 individuals, showing resulting genotypes and phenotypes for yellow and green peas.

    genetics mendel
  • A Revised Model

    Diagram illustrating a revised model of inheritance for the F3 generation, showing the genotypic ratios (1:2:1) and phenotypic ratios (3:1 Yellow:Green) resulting from self-fertilization.

    genetics inheritance mendel
  • Traits have two forms that can each breed true

    genetics mendel
  • The trait that appears in F1 progeny is the dominant form

    genetics mendel
  • The trait that is hidden in the F1 progeny is the recessive form

    genetics mendel
  • Progeny inherit one (elemente) unit from the maternal parent and the other unit from the paternal parent. These units remain discrete, and can reappear in the second generation.

    genetics mendel
  • Zygote: zugōtos (yolked), The cell created from the fusion of the egg and sperm/pollen.

    zygote genetics biology
  • Gametes: The specialized cells (egg and sperm/pollen) that transmit the heritable material from one generation to the next.

    gametes genetics biology
  • Gene: A locatable region of genomic sequence, corresponding to a unit of inheritance, which is associated with regulatory regions, transcribed regions and/or other functional sequence regions.

    gene genetics biology
  • Allele: Allelomorph - (allēlēn (of one another) and morphē (form), Alternate forms of the same gene.

    genetics vocabulary
  • homozygote: homos (same), Individuals with the same allele. ie. the purebreds - AA and aa.

    genetics vocabulary
  • heterozygote: hetro (different), Individuals with different alleles. ie. the hybrids - Aa

    genetics vocabulary
  • Vocabulary

    • Genotype - The alleles that are present, i.e. the genetics basis of the phenotype.
    • Dominant: The phenotype that is observed in the F1 progeny when 2 true breeding strains are crossed.
    • Recessive: The phenotype that is masked in the F1 progeny when 2 true breeding strains are crossed.
    genetics vocabulary
  • Mutation: an abrupt change in phenotype that can be inherited.

    Mutation: Heritable alterations in DNA sequence.

    genetics mutation
  • Often, mutation gets a bad connotation in the general public, so MD's often rename it

    • Genetic Variant
    • Disease Associated Variant
    • Genetic Change

    Image of Wolverine

    genetics mutation terminology
  • Title: The Punnett Square

    genetics punnett
  • Diagram transcript items: - Female - Male - Hermaphrodite - Eggs - Pollen Grains

    Diagram illustrating the Punnett Square method for predicting genetic crosses, showing parental gametes, F1 generation, and the resulting genotypes and phenotypes in the F2 generation.

    genetics gametes
  • In the formation of these cells, all elements participate in an entirely free and equal arrangement, by which it is only the differentiating ones which mutually separate themselves. Carl Correns 1900.

    genetics mendel
  • There are 2 alleles per parent, and each offspring gets one allele from each parent.

    genetics mendel
    • {{c1::Yellow (Y) is dominant to Green (y)}}
    genetics mendel
    • {{c1::Round (R) is dominant to Wrinkled (r)}}
    genetics mendel
  • F2 Results - 9 Yellow Round - 3 Green Round - 3 Yellow Wrinkled - 1 Green Wrinkled

    genetics mendel
  • Mendel's Dihybrid Cross, row RY across columns: - RRYY - RRYy - RrYY - RrYy

    genetics dihybrid
  • "...It is demonstrated at the same time that the relation of each pair of different characters in hybrid union is independent of the other differences in the two original parental stocks." Carl Correns 1900.

    genetics mendel
  • The segregation of one pair of alleles is not effected by the segregation of a second pair of alleles.

    genetics mendel
    • Law of Segregation
    • Law of Independent Assortment
    genetics mendel
  • Monohybrid

    genetics monohybrid
  • Dihybrid

    genetics dihybrid
    • 3:1
    • 9:3:3
    genetics ratios
  • Robert Brown describes the nucleus as a feature of all cells (Eukaryotes).

    cellbiology history
  • Theodor Boveri fertilizes the cytoplasm of a sea urchin egg with the sperm of a different species. The offspring have the traits of the sperm donor species and not the traits of the cytoplasm donor species. Thus supporting the idea that the nucleus determines the hereditary potential, not the cytoplasm.

    A photo of a sea urchin

    cellbiology inheritance experiment
  • Walther Flemming Describes Nuclear Cell Division (Mitosis).

    mitosis fleming
  • Heinrich Wilhelm Gottfried von Waldeyer-Hartz names the mitotic threads "chromosomes." For colored bodies.

    Microscopic images of cells undergoing mitosis, labeled with figure numbers

    chromosomes waldeyer-hartz
  • Measured the 22 Chromosomes of the lubber grasshopper, and found 11 specific sizes; therefore, predicting that Chromosome exist as identical pairs (Homologous Chromosomes).

    chromosome genetics
  • Followed the chromosomes through cell division, and observed that they paired up at the first meiotic division.

    meiosis chromosome
  • Gametes only get 11 chromosomes, and upon fertilization the chromosomes pair with 1 coming from the mother (Maternal) and one from the father (paternal).

    gametes fertilization
  • (Chromosomes) ... May constitute the physical basis of the Mendelian Law of Heredity.

    mendel theory
  • Thomas Hunt Morgan "The Boss"

    morgan genetics
  • Began studying the fruit (vinegar) fly in 1907, in an attempt to prove DeVries' Mutational Theory, which he thought would replace Mendelian Genetics.

    genetics history
  • He was very skeptical of the Chromosomal Theory.

    chromosomes genetics
  • Built a "Dream Team" at Columbia University.

    morgan history
  • Mutations lead to a change in phenotype

    mutations phenotype genetics
  • • Changes in DNA lead to Changes in RNA and protein.

    dna rna protein central_dogma
  • • RNA and protein are the direct output that leads to a phenotype.

    rna protein phenotype central_dogma
  • Diagram: DNA to RNA to Proteins

    Diagram showing the flow from DNA to RNA to Proteins, with labels for Replication, Transcription, and Translation

    The flow is DNA to RNA to Proteins (labels: Replication, Transcription, Translation).

    central_dogma diagram
  • Morgan's wife, Lillian and his undergraduate Calvin Bridges found the lab's first mutant fly.

    genetics
  • Its phenotype was white eyes instead of the normal red eyes.

    genetics
  • Bridges deduced that the gene encoding the white mutation was on the x chromosome.

    genetics chromosomes
  • Then demonstrated that the white mutation was inherited the same as the X-chromosome.

    genetics inheritance
  • Morgan was forced to accept the chromosomal theory based on this data.

    history chromosomal-theory
  • The DNA is usually in a relaxed conformation when a cell is not undergoing cell division (Chromatin).

    chromosome chromatin
  • Chromatin territories are arranged in the nucleus.

    Image of labelled chromatin territories

    chromatin nucleus
  • During Mitosis the DNA condenses (Winds up) to form a chromosome.

    mitosis chromosome
  • In a sexual diploid organism, you will have 2 chromosomes that have the same genes (a maternal and paternal copy). This is the basis for Mendelian Genetics.

    genetics mendelian
  • Each Chromatid represents one strand of DNA.

    chromosome genetics
  • Somewhere along the strand of DNA is a highly repetitive section of sequence called the Centromere.

    centromere chromosome
  • The short arm of the chromatid is called the p-arm, and the long is called the q arm.

    chromosome anatomy
  • During the S-Phase, the DNA strand is duplicated. The two strands are connected at the centromere. This is called a chromosome. and the two identical strands are called sister chromatids.

    s-phase chromosome cellcycle
  • When referring to the maternal and paternal copies of the chromosome, we call this a homologous chromosome.

    homologous genetics
  • Mendel Identified 7 phenotypes, and they all are on different chromosomes accept for Round/Wrinkles and Green Pod/Yellow Pod.

    mendel genetics chromosomes
  • Morgan's Dream Team Isolated ~85 mutations, and flies only have 4 chromosome pairs.

    morgan genetics chromosomes
  • How did Mendel get the results he did if Round and Green pod are on the same chromosome? Independent Assortment?

    genetics mendel
    • 9 Round Green
    • 3 wrinkled Green
    • 3 Round Yellow
    • 1 wrinkled yellow

    Illustrations of pea traits and gene pairs for seed shape and pod color

    genetics phenotypes
  • Occurs during Meiosis when there are 2 pairs of homologous Chromosomes called a tetrad.

    genetics recombination meiosis
  • Also called "Crossing Over"

    genetics terminology recombination
  • The percentage of crossing over between 2 genes is reproducible, and correlates with the distance between 2 genes on a chromosome.

    recombination genetics linkage
  • The Genetic Material is chromosomes.

    genetics
  • Each Chromosome has a maternal and paternal copy, their separation during cell division explains the law of segregation.

    chromosome
  • Recombination explains Mendel's Law of Independent Assortment.

    recombination
  • The Genetic Material is found in the nucleus of the cell.

    cell
  • Note - Based on subsequent experiments (Avery, McCarthy, and MacLeod; Hershey and Chase), we know that DNA is that molecule.

    dna
  • "Hey! What's this Drosophila melanogaster doing in my soup?"

    cartoon farside
  • What is this famous picture to the right?

    X-ray diffraction pattern

    Photo 51

    dna photo51 xray
  • How was it taken?

    A circular X-ray diffraction pattern

    dna xray diffraction
  • DNA Structure

    dna structure
  • {{c1::"Almost all aspects of life are engineered at the molecular level, and without understanding molecules, we can only have a very sketchy understanding of life itself."}} - Francis Crick

    quote crick dna
  • Chemical constituents of DNA

    DeoxyribosePhosphateFour nitrogenous bases:Purines: guanine (G)adenine (A)Pyrimidines: cytosine (C) and thymine (T)

    dna biochemistry genetics
  • • {{c1::Linked 5' to 3' in a directionality}}

    dna structure
  • Ratios of bases: A:T ratio is 1:1, G:C ratio is 1:1

    genetics dna chargaff
  • Ratios of A:G is dependent on species.

    genetics dna chargaff
  • {{c1::Wilkins started the project and collected the DNA and first x-ray diffractions.}}

    genetics dna
  • {{c1::R. Franklin and Gosling collected the X-ray diffraction pattern of DNA (Picture 51).}}

    genetics dna
  • Watson and Crick {{c1::described the structure as a anti-parallel double helix, point out base complementarity, and suggest a method by which replication could occur.}}

    genetics dna structure
  • Watson, Crick, and Wilkins won Noble of 1962. Franklin had already died of cancer by this time.

    genetics history dna
    • Watson and Crick Model
    dna structure genetics
    • Right handed (clockwise)
    • Double helix (Not 3)
    • Anti-parallel
    dna structure properties
    • Major groove and minor groove selective for DNA binding.
    dna grooves binding
    • 1 complete turn for every 10 Residues
    dna geometry structure
  • • 2 Strands are held together with hydrogen bonds.

    dna double-helix
    • A=T is 2 bonds
    • G=C is three bonds
    dna base-pairing chargaff
  • Major and minor groove facilitated by base structure.

    dna structure grooves
  • • Complementary binding* • Complementary - to make wholeComplimentary - to give someone a compliment

    vocabulary dna terminology
  • "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." Watson and Crick 1953

    biology dna replication
  • Base letters and names shown: Stylized depiction of a DNA double helix with labeled base pairs (A-T, G-C), and individual bases.

    • A Adenine
    • C Cytosine
    • G Guanine
    • T Thymine

    Base pairings shown: A-T, G-C

    biology dna bases base-pairing
  • IT'S NOT SUPPOSED TO BE A TRIPLE HELIX, IS IT?

    cartoon quote
  • Yellow (Y) is dominant to Green (y)

    genetics dominance
  • There are many genes per chromosome!

    genetics chromosome
  • Each yellow bar represents a gene that encodes a protein.

    Genome browser view showing gene predictions along Chromosome 1 with scale markers.

    genetics genes
  • Genome: The unique genetic content of an organism in its entirety.

    genome genetics definition
  • For humans this is the haploid set of information, i.e. one copy of every nucleotide (gamete) ~3,381,944,086 bp.

    human genome genetics
  • Homologous Chromosomes - Same genes, same order

    genetics chromosomes
  • Different DNA sequences - Allele A - Allele B

    genetics alleles
    • Mendel's Traits can be explained by simple sequence changes in the alleles.
    genetics alleles mendel
  • Examples of sequence changes in alleles: - {{c1::Round V. Wrinkled — Starch branching enzyme 1 — 0.8-kb insertion}} - {{c1::Tall vs. Short — GA 3-oxidasel — G-to-A substitution}} - {{c1::Yellow Pea vs. Green Pea — Stay-green gene — 6-bp insertion}} - {{c1::Purple Flower vs. White Flower — bHLH transcription factor — G-to-A substitution}}

    genetics alleles mutations
    • The Sequence for the Round Gene (R) encodes a protein that can make complex starches
    • The sequence for the Round gene (r) makes a protein that doesn't work.
    biology genetics peas
  • The amount of starch in the pea cells affects osmosis (more water rushes in stretching the size of the pea overall). As it is dehydrated for storage the pea wrinkles.

    biology genetics peas
  • Genotype RR: - Copy 1 Active enzyme - Copy 2 Active enzyme - Phenotype Branched starch

    genetics mendel
  • Genotype Rr: - Copy 1 Active enzyme - Copy 2 Inactive enzyme - Phenotype Branched starch

    genetics mendel
  • Genotype rr: - Copy 1 Inactive enzyme - Copy 2 Inactive enzyme - Phenotype Unbranched starch

    An illustration of unbranched starch

    genetics mendel
  • Cartoon caption: I WOULDN'T CALL THIS THE BUILDING BLOCK OF LIFE — IT'S MORE LIKE THE ROPE THAT TIES IT TOGETHER.

    cartoon dna quote
  • Non-repeated or single copy DNA (Genes)

    • Only ~1.5%

    A bar chart showing the percentage of DNA not coding for protein across different organisms.

    biology genetics
  • Easiest way to look at structure is by taking something apart and putting it back together.

    structure
  • DNA Renaturation: Cooling of DNA leads to reassembly of the double helix by binding of complementary sequences. Also called reannealing. Lead to the development of in situ hybridization.

    dna hybridization renaturation
    • {{c1::256 genes in Mycoplasma genitalium (Minimal Genome
    • 6,600 genes in yeast.
    • ~20,000 genes in humans.
    • ~57,000 genes in Apple}}
    genetics genes
  • Sometimes we find more than 2 copies of the gene!

    genetics
    • rRNA's
    • Histones
    molecular
  • Does everyone in this room have the same sequence of nucleotides for every gene?

    genetics
  • Does every cell in your body have the exact same genome?

    genome
  • If not, what might be sources of variability?

    variability
  • Genetic Polymorphism - Sites in the genome that vary among individuals. Occur >1% of the population.

    genetic polymorphism
  • Single Nucleotide Polymorphisms (SNPs) - Most common genetic variability between organisms.

    snps genetics
  • If comparing 2 individual genomes there maybe as many as 3 million SNPs that are different. ~1/1000 bp

    snps frequency
  • DNA is composed of a deoxyribose phosphate backbone that is assembled with a 5' to 3' directionality that is assembled as an anti-parallel helix

    dna structure
  • The Nitrogenous bases reside internally, and are held together in a complementary relationship by hydrogen bonds. 3 for GC and 2 for AT.

    dna bases
  • For most of the cell's life, DNA remains in a relaxed state called chromatin, and this resides in specific territories in the nucleus.

    chromatin nucleus
  • Each strand of DNA represents a chromatid. 2 chromatids held together at the centromere is a chromosome. 2 chromosomes (Maternal and Paternal Copies) are homologous chromosomes.

    chromosome chromatid homologous
  • A complete set of all the genes in the organism is the genome.

    genome
  • Genes can be identified by hybridization (complementary base pairing).

    genes hybridization
  • Cartoon of two DNA double helices. The taller one has a flower on top and asks, 'Do these genes make me look fat??'

    Cartoon of two DNA double helices with the taller one asking, 'Do these genes make me look fat??'.

    genetics cartoon
  • Can we determine how closely species are related to each other by their genes?

    biology genetics evolution
  • Gene sequences are conserved across multiple species.

    genes evolution
  • This might be due to an evolutionary relationship (homologous genes).

    homologous genes are defined as copies of the same gene separated by a speciation event.

    genes evolution
  • SHH, H. sapiens, SHH, P. troglodytes, sonic hedgehog, SHH, M. mulatta, sonic hedgehog, SHH, C. lupus, SHH, B. Taurus, sonic hedgehog, Shh, M. musculus, sonic hedgehog, SHH, R. norvegicus, shh, G. gallus, shh, X. tropicalis, sonic hedgehog, shha, D. rerio, sonic hedgehog a, shhb, D. rerio, sonic hedgehog b, hh, D. melanogaster, hedgehog, AgaP_AGAP001412, A. gambiae.

    homologous genes shh
  • Gene Trees are hypotheses on the evolutionary relationship between organisms based on their sequence identity.

    evolution genes
  • Most trees utilize amino acid sequence; however in some cases rRNA or other RNA sequences may be used.

    phylogeny sequences
  • Can we make a gene tree for SHH?

    shh genes
  • Gene Trees are a hypothesis, as they may vary from gene to gene.

    evolution genetree
  • Other data is often brought into determine Evolutionary arrangements.

    evolution genetree
  • Sometimes these changes can be very informative for determining what makes two species different.

    evolution comparative
  • Human or Chimp FoxP2 sequence and placed it into human cells.

    foxp2 experiment
  • Over 100 genes were altered in their expression (The ones made into RNA), specifically those involved with formation of the vocal centers of the brain and the voice box.

    gene_expression vocalization
  • Other genes that show this accelerated change between chimp and human often involve changes in the brain.

    brain evolution
  • Homologous genes are copies of genes that are separated by a speciations event.

    genetics evolution
  • For proper function, protein sequences do not change; therefore, we can measure gene conservation between species.

    molecular conservation
  • This can give us a hypothesis as to their evolutionary relationship; however other data maybe needed.

    evolution phylogeny
  • Some of the changes between genes is highly informative defining what amino acids are critical for function, and in some cases these alterations may have helped define the traits that led to speciation.

    protein evolution
  • Gene order (Synteny) can provide a useful secondary tool for determining evolutionary relationships.

    synteny genomics
  • Myoglobin Gene Tree showing evolutionary relationships of Myoglobin proteins from Human, Horse, Sperm Whale, Sea Turtle, and Tuna.

    biology evolution myoglobin
  • DNA in the nucleus undergoing transcription to mRNA, mRNA being translated in the cytoplasm to protein.

    centraldogma molecularbiology
  • Proteins then travel through ER and Golgi for secretion or signaling.

    protein trafficking
  • Includes labels for Nucleus, Cytoplasm, DNA of chromosome, Pre-mRNAs, Segment of DNA being transcribed, mRNAs, mRNA being translated, Protein, ER, Golgi, Cytoskeleton, Receptor for signal from other cell, and Cell Signal to other Cell.

    labels diagram
  • Cytoskeleton Alterations lead to communication.

    cytoskeleton signaling
  • The circular diagram illustrates the flow of information from DNA to RNA to Protein.

    centraldogma flow
  • The Flow of Information: a principle or set of principles laid down by an authority as incontrovertibly true.

    definition centraldogma
  • The Central Dogma: "Once information has got into a protein it can't get out again".

    biology centraldogma
  • Information here means the sequence of the amino acid residues, or other sequences related to it.

    biology centraldogma
  • Transcription: - DNA -> RNA - {{c1::Same language of nucleotides}}

    transcription genetics
  • JULIET: - O happy dagger, - This is thy sheath. - There rust and let me die.

    literature romeoandjuliet
  • Juliet says to someone: "Go, get thee hence, for I will not away."

    literature shakespeare romeojuliet
  • Observation about Romeo's death: "Poison, I see, hath been his timeless end."

    literature shakespeare romeojuliet
  • Juliet's plan before she kills herself: "O churl, drunk all, and left no friendly drop To help me after?"

    literature shakespeare romeojuliet
  • "O happy dagger, This is thy sheath." — Juliet's final words before she stabs herself.

    literature shakespeare romeojuliet
    • Genes make proteins
    genetics centraldogma
    • Genes are located on Chromosomes in the nucleus

    Diagram of three stylized figures, a red one in the center flanked by two white ones who shake his hand.

    genetics chromosomes nucleus
    • Proteins are made by Ribosomes in the cytoplasm.
    protein ribosome cytoplasm
    • 1950's - Each gene makes a specific ribosome which produces the protein.
    history genetics ribosome
  • Volken and Astrachan demonstrated that when phage infect bacteria, RNA is made that is a very small fraction of total cell RNA.

    volken astrachan phage rna
  • Belozersky and Spirin determine the base composition of ribosomes was similar in may species of bacteria while the base composition of their DNA was different.

    belozersky spirin ribosomes dna
  • Jacob, Monod, and Pardee collected data that led Jacob to suggest that maybe there is a short term intermediate that is mediating this rather than unique ribosomes being made.

    jacob monod pardee intermediate
  • Brenner and Crick realized that Volken and Astrachan's small fraction of RNA was the intermediate that could explain Jacob's data.

    brenner crick rna intermediate
  • Filter homogenate to remove clumps of unbroken cells, connective tissue, etc. -> Filtered homogenate

    centrifugation cellbiology
  • 600 gx 10 min -> Nuclei

    centrifugation cellbiology
  • 15,000 g x 5 min -> Mitochondria, chloroplasts, lysosomes, and peroxisomes

    centrifugation organelles
  • 100,000 g x 60 min -> Plasma membrane, microsomal fraction (fragments of endoplasmic reticulum), and large polyribosomes

    centrifugation organelles
  • 300,000 gx 2 h -> Ribosomal subunits, small polyribosomes

    Soluble portion of cytoplasm (cytosol) -> Soluble portion of cytoplasm (cytosol)

    Diagram outlining the Differential Centrifugation method.

    centrifugation cytosol organelles
  • Cellular components can be separated by {{c1::how fast they sediment}} in a thick solution during a {{c1::high speed centrifugation}}.

    centrifugation cellular_components
  • If these components are labeled they can easily observed as you {{c1::empty the centrifugation tube}}.

    observation lab_technique
  • Zonal centrifugation

    {{c1::Particles migrate according to S-value}}

    Sucrose density gradient

    zonal centrifugation
  • Isopycnic centrifugation

    {{c1::Particles distributed according to density}}

    CsCl density gradient

    isopycnic centrifugation
  • Grew E. coli in C14/S35 to make heavy (not radioactive)

    experiment e.coli labeling
  • Moved E. coli to C12/S32/P32 and injected with phage.

    experiment e.coli phage
  • Wait 1 hour then Homogenize cell components and separate with CsCl2 centrifugation.

    experiment protocol centrifugation
  • MODEL I (one-ribosome-one-protein)

    MODEL III (messenger RNA)

    models centraldogma geneexpression
  • Demonstrates that mRNA Is the molecule produced upon infection and is the intermediate!

    centraldogma
  • Experiment components: - mRNA Ribosome complex - C12/S32/P32 - Large Ribosome (Heavy) C14/S35 - Small Ribosome (Heavy) C14/S35 - mRNA - P32 labeled (Light) C12/S32

    Diagram showing a labeled diagram of test tubes representing different molecular components after centrifugation.

    experiment
  • Messenger RNA (mRNA): Transfers information from DNA in the nucleus to ribosomes in the cytoplasm.

    biology rna
  • Ribosomal RNA (rRNA): Structural component of the Ribosomes.

    biology rna
  • Transfer RNA (tRNA): {{c1::Translates the mRNA code into the amino acid code.}}

    biology rna
  • Other Types of RNA

    • small nuclear RNA (snRNA) - Catalyzes reactions for mRNA synthesis.
    • small nucleolar RNA (snoRNA) - Regulates rRNA synthesis
    • small interfering RNA (siRNA) -{{c3::Regulates Transcription and Translation.}}
    • micro RNA (miRNA) - Regulates Transcription and Translation.
    • long noncoding RNA (lncRNA) - Regulates Transcription
    • piwi Interacting (piRNA) - Regulates Transcription.
    rna molecular_biology
  • 1° Structure

    {{c1::Sugar phosphate backbone}}

    rna structure
    • Adenine
    • Cytosine
    • Uracil
    • Guanine
    rna bases
  • Garrod Hypothesized that genes encode enzymes.

    genetics history
  • Beadle and Tatum Proved Genes encode enzymes.

    genetics experiments
  • Crick proposed the Central Dogma for flow of information.

    DNA->RNA->Protien

    centraldogma molecularbiology
  • Brenner, Medelson, Jacob, and Monod Identified mRNA.

    rna history
  • RNA is a diverse set of molecules that can have many functions in regulating information flow and metabolism.

    RNA is a diverse set of molecules that can have many functions in regulating information flow and metabolism.

    rna function
  • Rapidly Expanding field related to RNA function.

    Rapidly Expanding field related to RNA function.

    rna field
  • Arthur, the mRNA, was at the end of his strand at work.

    mrna molecular-biology
  • I'm DONE being this guy's messenger boy.

    messenger phrase
    • Receptor for signal from other cell.
    signaling
  • Sequence of information (central dogma fragments): - {{c1::DNA of chromosome}} - Pre-mRNAs - mRNA being translated Protein

    centraldogma
    • Cytoplasm
    • Nucleus
    • Golgi
    • ER
    • Cytoskeleton
    organelles
  • {{c1::Alterations lead to communication}}

    communication
  • Based on what we learned previously (for example, glycolysis, cell signaling), What do you think will facilitate RNA transcription?

    biology transcription exam
  • The making of mRNA is Catalyzed by enzymes called the DNA-Dependent RNA polymerase

    biology molecular
  • Transcription (General Features): - Specifically Recognize the start of a gene. - Unwind the DNA. - Synthesize new RNA complementary to the DNA template. - Proofread to make sure it copied the sequence correctly - Completion - rewind DNA and release RNA.

    genetics biology transcription
  • The steps of transcription are: - Specifically Recognize the start of a gene. - Unwind the DNA. - Synthesize new RNA complementary to the DNA template. - Proofread to make sure it copied the sequence correctly - Completion - rewind DNA and release RNA.

    transcription centraldogma molecularbiology
  • Most genetic information is "read" from unwound DNA e.g. synthesis of DNA or RNA

    dna genetics
  • Some genetic information is accessible within double-stranded DNA e.g. DNA-binding proteins that regulate gene expression

    dna gene_expression
  • Purines: - A - Guanine (G)

    Pyrimidines: - Thymine (T) - Cytosine (C)

    dna bases
  • Promoter: Sequence of DNA that encodes for transcription to start.

    promoter transcription
    • Provides binding site for Proteins that can turn Transcription on or off (Sigma or Transcription Factors).
    • Help RNA polymerase bind to the template DNA.
    • Step 1 of Transcription is to bind to the DNA at the promoter site.
    promoter transcription
Study Notes

Cell signaling — overview

  • Major receptor classes: ligand-gated ion channels, G-protein coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), steroid (nuclear) receptors, and other protein-stability/signaling systems.
  • Common mechanisms: second messengers (e.g. cAMP, Ca2+), phosphorylation/dephosphorylation, GTP/GDP exchange, proteolytic activation, and regulated proteolysis.

Notch, protease signaling, and regulated cleavage

  • Notch signaling: direct cell–cell contact; ligand (Delta) binds Notch, proteolytic cleavages release Notch intracellular domain (NICD) that moves to nucleus and modulates transcription with CSL, MAML, co-repressors/co-activators.

Notch signaling diagram

  • Key idea: proteolysis can be the signaling event; both cleavage fragments sometimes carry information.

Proteolytic cascades and apoptosis

  • Procaspases → caspases: many proteases are made as inactive zymogens; cleavage activates them and can generate amplification cascades.

Procaspase activation diagram

  • Caspase cascade: one active caspase can activate many downstream caspases, leading to cleavage of cytosolic proteins and nuclear lamins and driving programmed cell death.

Caspase cascade

  • Initiation routes: extrinsic (death receptors, e.g. TRAIL–DR5 → FADD → caspase-8) and intrinsic (mitochondria/nucleus signals) converge on executioner caspases.

Apoptosis initiation (TRAIL-DR5)

WNT signalling (stabilization by inhibition of proteolysis)

  • Core idea: Wnt binds Frizzled/LRP6 → recruits Dishevelled/Axin/APC complex → prevents beta‑catenin proteolysis, allowing beta‑catenin to accumulate, enter nucleus, and activate TCF target genes.

WNT signaling diagram

Signaling takeaways

  • Signals travel by conformational change, covalent modification (phosphorylation), nucleotide exchange (GTP/GDP), or proteolysis.
  • Pathways interact extensively; outcomes depend on network context and amplification steps.

Mendel and foundations of classical genetics

Mendel's approach

  • Systematic record-keeping, counting individuals, making predictions from clear hypotheses.
  • Phenotype = observable trait; genotype = underlying allele composition.

Key definitions

  • Allele: variant form of a gene. Homozygote = same alleles (AA or aa), heterozygote = different (Aa).
  • Dominant: phenotype observed in F1 of two true-breeding parents; recessive: masked in F1.
  • Mutation: heritable change in DNA sequence (also called variant).

Mendel's results (single- and two-trait crosses)

  • Monohybrid F2 phenotypic ratio: \(3:1\) (dominant:recessive).
  • Dihybrid F2 phenotypic ratio: \(9:3:3:1\) when genes assort independently.

Mendel pea cross (P → F1 → F2)

Laws

  • Segregation: each parent carries two alleles but passes one allele to offspring.
  • Independent assortment: alleles of different genes segregate independently, explained by recombination when genes are on different chromosomes or sufficiently far apart.

Punnett squares & prediction

  • Punnett squares enumerate gamete combinations and show expected genotype/phenotype ratios in offspring.
  • Use genotype tables to distinguish AA, Aa, aa and predict phenotypes.

Chromosomes, recombination, and the physical basis of heredity

  • Chromosomal theory: chromosomes carry genes; homologous chromosomes (maternal + paternal) segregate in meiosis explaining Mendel's segregation.
  • Thomas Hunt Morgan: linked traits to chromosomes (X-linked white eye in Drosophila) showing gene location matters.
  • Genetic recombination (crossing over) occurs in meiosis between homologs; recombination frequency correlates with physical distance and creates new allele combinations that underlie independent assortment for linked genes.

Takeaway

  • Chromosomes are the physical substrate for Mendel's laws; recombination explains observed ratios for genes on the same chromosome.

DNA structure — essentials

  • Building blocks: deoxyribose sugar, phosphate, four bases A, G (purines) and C, T (pyrimidines); backbone has 5'→3' directionality.

DNA strand and bases

  • Chargaff rules: in double-stranded DNA, \([A]\\approx[T]\) and \([G]\\approx[C]\) (species-dependent A:G ratio).
  • Watson–Crick model: right-handed, antiparallel double helix with major/minor grooves, A–T (2 H‑bonds), G–C (3 H‑bonds); ~10 bp per turn.

DNA double helix model

  • Famous evidence: Rosalind Franklin’s Photo 51 (X-ray diffraction) supported the helical structure.

Photo 51 X-ray diffraction pattern

Genome facts

  • Genome = complete set of genetic information; human haploid genome ≈ \(\(3,381,944,086 ext{ bp}\)\).
  • Only ~1.5% of the human genome codes for proteins; gene counts vary (~20,000 protein-coding genes in humans).

Genes, alleles, and simple molecular examples

  • Alleles are sequence variants at the same locus; small insertions/substitutions can explain classic Mendel traits.
  • Example (pea seed shape): the dominant allele (R) encodes an active starch‑branching enzyme producing branched starch → round peas; recessive (r) lacks activity → wrinkled peas.

Round vs wrinkled pea mechanism


The Central Dogma & RNA

  • Central Dogma: information flows DNA → RNA → Protein.

Central Dogma diagram

  • Key RNAs: mRNA (messenger), rRNA (ribosomal), tRNA (transfer); many regulatory RNAs (miRNA, siRNA, lncRNA, snoRNA, snRNA, piRNA).

Evidence for mRNA as the intermediate (classic experiment)

  • Meselson/Steel/Brenner/Jacob type experiments (infected E. coli with phage) used differential labeling and centrifugation to show a short-lived RNA is produced upon infection and associates with ribosomes — that is mRNA as the transient intermediate.

mRNA–ribosome centrifugation result

Transcription — basic steps

  1. Promoter recognition by RNA polymerase + transcription factors.
  2. DNA unwinding locally to expose template strand.
  3. RNA synthesis 5'→3' complementary to the DNA template.
  4. Proofreading/error checking (limited compared to DNA polymerases).
  5. Termination, release of RNA, and DNA re‑annealing.

Quick study tips

  • Memorize Mendel ratios and what they indicate (segregation vs independent assortment).
  • Understand the physical relationship: gene ↔ chromosome ↔ DNA ↔ sequence variant (allele).
  • Practice translating simple genotypes to phenotypes (AA, Aa, aa) and drawing Punnett squares.
  • For signaling, focus on mechanism classes (phosphorylation, GTP switches, proteolysis) and examples (Notch, Wnt, caspase cascade).

Suggested quick review questions

  • Explain how recombination produces the 9:3:3:1 dihybrid ratio for unlinked genes.
  • Compare extrinsic vs intrinsic apoptosis initiation.
  • Describe the evidence (Photo 51 + Chargaff) that supported the double helix model.
  • Outline the five general steps of transcription.