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Exam 2 Content, Nucleotides: monomer of DNA - Coggle Diagram

- - - - 1) DNA should have 1:1 ratio of purines/pyrimidines
      - 2) %A=%T; %C=%G
  - - - This discovery refers to B-DNA
        
        10 base pairs per rotation
        
        right-handed
        
        other (rarer) forms of DNA also exist
        
        A-DNA: shorter/wider, caused by presence of less water
        
        Z-DNA: left-handed
        
        H-DNA: three-stranded (triplex) formed when DNA unwinds and one strand pairs with another double-stranded DNA
        
        often occurs in long sequences of only purines or only pyrimidines
        
        exists when plenty of water surrounds the molecule and there are no unusual base sequences
  - - - because only DNase destroyed transforming substance
  - - - helps to explain
      - repeated in tandem
      - clustered in certain regions of chromosome, especially centromeres/telomeres
    - - includes most sequences that encode proteins
      - seen 1-2% in genome
    - - Tandem Repeats: appear one after the other, tend to bee clustered at particular locations on the chromosome
      - Interspersed Repeats: scattered throughout genome
        
        Short Interspersed Elements (SINEs)
        
        Long Interspersed Elements (LINEs)
  - - - Eukaryotic Chromosomes
        
        have several
        
        both contain DNA
        
        Bacterial Chromosomes
        
        most consist of a singular circular DNA molecule
        
        DNA appears as distinct clump, called the nucleoid, which is confined to a definite region of the cytoplasm
        
        packing of eukaryotic DNA (tertiary structure) changes regularly in response to cell cycle
        
        linear DNA
        
        contains centromere
        
        Centromere Structure: constricted region of chromosome (heterochromatin) where spindle fibers attach
        
        loss of centromere means chromosome will not segregate into nucleus in mitosis and is usually lost
        
        has telomeres
        
        Telomere Structure: ends of chromosome, stabilize and provide means to replicate the ends of linear chromosomes
        
        sequences with a series of A or T nucleotides followed by several G nucleotides
        
        very repetitive - don't code for anything
        
        always oriented so that the string of Gs and Cs is toward end of chromosome
        
        Chromosomes made up of chromatin (complex of DNA and proteins)
        
        Euchromatin: undergoes normal process of condensation and decondensation in cell cycle
        
        Heterochromatin: remains in highly condensed state throughout the cell cycle
        
        major protein component of chromatin
        
        Histones: small, positively charged proteins (due to abundance of + charge amino acids)
        
        Five Major Types: H1, H2A, H2B, H3, H4
        
        Levels of Organization for Chromatin Structure
        
        Simple Level: DNA double helix
        
        Complex Level: DNA closely associated with proteins, highly folded to produce chromosome
        
        High-Order Chromatin Structure
        
        300nm loops
        
        30nm fiber
        
        250nm-wide fiber
        
        Nucleosome: fundamental repeating unit of chromatin
        
        consists of DNA wrapped about two times (200 bp) around an octamer of 8 histones
        
        two copies each of H2A, H2B, H3, H4
        
        H1 histone is not part of nucleosome structure, instead binds to where DNA joins octamer, acting as a clamp to hold it in place
        
        each histone has a positively charged amino acid tail that interacts with the negative phosphate of DNA to keep it in place
        
        electrostatic attraction
        
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        located at regular intervals along DNA, separated by linker DNA
        
        changes in chromatin structure allows for replication/transcription
        
        Polytene Chromosome (Chromosomal Puffs): localized swelling caused by regions of chromatin with relaxed structure, regions of active transcription
        
        chromatin is more exposed during active transcription
        
        leads to
        
        DNase I Sensitivity
        
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  - - - Positive Supercoiling: overrotated
      - Negative Supercoiling: underrotated
        
        most DNA found in cells is negatively supercoiled
        
        can be packed into smaller space than relaxed DNA
        
        makes separation of two DNA strands easier during replication/transcription
  - - - melting temp: more H-bonds, higher melting temp
        
        more energy needed to separate C&G (3 H-bonds) than A&T (2 H-bonds)
- - - - in division of heteroplasmic cells, organelles separate randomly (replicative segregation)
    - - occurs by chance
  - - - slow growth, defective ATP production
      - can't carry out aerobic respiration
  - - - encodes 2 rRNAs, 22 tRNAs, 13 proteins
      - highly economical in organization
        
        few noncoding regions between genes
        
        almost all mRNA codes for proteins
    - - accelerated rate of evolution in vertebrate mtDNA due to high mutation rates
        
        in spite of this, number of genes and organization remains relatively consistent
      - mtDNA is ideal for reconstructing evolution patterns in humans and other organisms
        
        small size and abundance
        
        maternal inheritance makes it possible to trace female lines of descent
        
        abundance of mtDNA, thousands of copies per cell
    - - many human genetic diseases associated with mtDNA appear in middle age or later
      - oxidative phosphorylation capacity (ATP synthesis) declines with age
        
        those with mtDNA mutation start with limited capacity
  - - - more stable as nuclear DNA, fewer mutations
- - - - one error/ million bp leads to 6400 mistakes every time a cell divides, which would be catastrophic
    - - E. Coli replicates its DNA at a rate of 1000 nucleotides/second
  - - - one round yields two 50/50 molecules
      - two rounds yields two 50/50 molecules and two entirely new molecules
    - - used two types of nitrogen (because nucleotides have nitrogenous bases)
        
        14N: common form, 15N: rare heavy form
      - culture E. Coli were subjected to equilibrium density gradient centrifugation
        
        after one round, one intermediately weighted band
        
        after additional rounds, two bands: on lighter, one intermediate
  - - - each replicon contains an origin of replication
    - - usually bidirectional replication (can be unidirectional)
      - origin of replication forms replication fork
      - occurs in circular DNA
      - no breakage of nucleotide strand
      - the products are two circular DNA molecules
      - one replicon
    - - viruses and F factor of E. Coli
      - single origin of replication
      - unidirectional
      - products are one circular molecule and one linear molecule that may circularize
      - breakage of nucleotide strand
      - one replicon
    - - occurs in eukaryotic cells
      - many replicons
      - bidirectional
      - two linear molecules
      - products are two linear molecules
  - - - DNA Polymerase I: primarily for RNA primer removal and replacement
        
        5'--->3' polymerase activity to add new nucleotides
        
        3' ---> 5' exonuclease activity used to correct errors
        
        5'--->3' exonuclease activity used to remove primers laid down by primase
      - DNA Polymerase III: large multiprotein complex that acts as the workhorse of replication
        
        5'--->3' polymerase activity adds new nucleotides
        
        3'---->5' exonuclease activity to correct errors
    - - Leading strand used as template for continuous synthesis in 5'--->3' direction
      - Lagging strand used as template for discontinuous replication
        
        short lengths of DNA on the lagging stands are called Okazaki fragments
        
        DNA Ligase seals the lagging strand by catalyzing formation of phosphodiester bonds
    - - Initiation
        
        Initiator Proteins: bind to the OriC and cause a short section of DNA to unwind
        
        this unwinding allows helicase and other single-stranded binding proteins to attach to the polynucleotide strand
      - Unwinding: DNA must be unwound to display single-stranded replication templates
        
        DNA Helicase
        
        breaks H-bonds that exist between bases of two nucleotide strands
        
        cannot initiate unwinding in bacteria (initiator protein does this)
        
        moves in 5'--->3' along replication fork
        
        Single-Strand Binding Proteins (SSBs)
        
        After DNA has been unwound by helicase, SSBs attach to exposed single-stranded DNA
        
        protect single-stranded nucleotide chains and prevent formation of secondary structures (such as hairpins) that would interfere with replication
        
        indifferent to base sequence, will bind to any single-stranded DNA
        
        DNA Gyrase
        
        type II topoisomerase
        
        in replication, it reduces the torsional strain builds up ahead of the replication fork as a result of unwinding - DNA Gyrase relieves the strain
        
        makes double-strand break, passes another segment of helix through the break, then reseals it
        
        this action requires ATP
      - DNA Synthesis
      - Termination: occurs when two replication forks meet, or at occurrence of termination sequences
        
        Fidelity of DNA Replication: error rate extremely low
        
        Proofreading: the 3'--->5' exonuclease
        
        Mismatch Repair: corrects errors (secondary structure deformities) after replication is complete
        
        requires ability to distinguish between new and old DNA
  - - - ORC (origin replication complex) binds to ARS to initiate DNA replication
    - - MCM (minichromosome maintenance): binds DNA and initiates replication as helicase on all origins
    - - Alpha
        
        Initiation of nuclear DNA synthesis and DNA repair
        
        5'-->3' polymerase activity
      - Delta
        
        5'---->3' polymerase activity
        
        3'--->5' exonuclease activity
        
        Lagging-strand synthesis of nuclear, DNA repair, DNA synthesis
      - Epsilon
        
        5'--->3' polymerase activity
        
        3'--->5' exonuclease activity
        
        leading-strand synthesis
    - - occurs in 3 steps
        
        disruption of original nucleosomes on the parental DNA
        
        Redistribution of existing histones on the new DNA molecules
        
        addition of newly synthesized histones to complete the formation of new nucleosomes
- - - - loss of one chromosome
        
        Monosomy
      - Gain of one chromosome
        
        Trisomy
      - loss of homologous pair
        
        Nullisomy
      - gain of homologous pair
        
        Tetrasomy
      - Effects of Aneuploidy
        
        Sex-Chromosome Aneuploids
        
        Turner Syndrome: XO
        
        Klinefelter Syndrome: XXY
        
        Uniparental Disomy: both chromosomes inherited from one parent, none from the other
        
        can result in recessive traits coming through when only one parent is a has them
        
        Trisomy 21: most common human aneuploid
        
        Primary Down Syndrome: 75% nondisjunction in egg formation
        
        Familial Down Syndrome: Robertsonian translocation between chromosomes 14 and 21
      - Causes of Aneuploidy
        
        robertsonian translocation (lose chromosome)
        
        nondisjunction during meiosis/mitosis (loss and gain of chromosomes)
        
        deletion of centromere during meiosis/mitosis (lose chromosome)
  - - - sets from more than one species
        
        Allopolyploidy
        
        allotetraploids: functionally diploid
      - all sets from one species
        
        Autopolyploidy
        
        autotriploids: sterile
        
        caused by nondisjunction
  - - - deletion of chromosome segment
        
        Deletion
        
        Large deletions easily detected (normal chromosome loops out)
        
        Effects of Deletions
        
        Pseudodominance: expression of a normally recessive gene if dominant gene is deleted in heterozygote
        
        Imbalances in gene product (loss of protein product)
        
        Haploinsufficiency: a single gene is not sufficient to produce WT phenotype, so even with one WT gene present the mutant phenotype is expressed
      - Duplication of chromosome segment
        
        Duplication
        
        Tandem Duplication: duplicated segment adjacent to original segment
        
        Displaced Duplication: duplicated segment is some distance away from the original segment (can be on same chromosome or different chromosome)
        
        Arises from unequal crossing over
        
        Reverse Duplication: sequence of duplicated segment is inverted relative to the sequence of the original segment
        
        Effects of Duplication
        
        In meiosis (for heterozygotes) duplicated region must loop out
        
        reasons for chromosomes looping out
        
        unbalanced gene dosage
        
        Effects phenotype (Ex. barr mutation in fruit flies, incomplete dominant x-linked mutation)
      - inversion of chromosome segment
        
        Inversion
        
        Paracentric Inversion: does not include centromere
        
        Pericentric Inversion: includes centromere
        
        Inversions in Meiosis
        
        Heterozygous Individuals: homologous sequences only align if the two chromosomes form an inversion loop
        
        Paracentric Inversion: has dicentric chromatic
        
        Two nonviable recombinant genes, one normal nonrecombinant, one nonrecombinant with inversion
        
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        Pericentric Inversion: no dicentric chromatid
        
        Homozygous Individuals: no problems arise during meiosis (can still have phenotypic consequences)
      - movement of chromosome segment
        
        Translocation
        
        Reciprocal Translocation: with reciprocal exchange
        
        Nonreciprocal Translocation: without reciprocal exchange
        
        Robertsonian Translocation: translocation of acrocentric chromosomes
        
        long arms of two acrocentric chromosomes become joined to a common centromere, short arms are lost
        
        Results in overall reduction of chromosome number (deletion)
        
        Translocations in Meiosis
        
        Alternate Segregation: viable
        
        Adjacent 1/2: nonviable
- - - - Competent Cells: have ability to take up DNA from environment
      - Transformants: cells that receive genetic material
      - Cotransformed: cells that are transformed by two or more genes
      - can occur with virtually any type of DNA
      - Gene Mapping with Transformation
        
        Gene Mapping
        
        Requires two strands of bacteria that differ in several genetic traits (Ex. a-b-c- X a+b+c+)
        
        Bacterial genes can be mapped by observing the rate at which they are cotransformed
        
        Genes that are closer together are more likely to be transferred together
  - - - usually occurs between bacteria of same or closely related species
      - Generalized Transduction: any gene may be transferred
      - Specialized Transduction: only a few genes are transferred
      - Gene Mapping with Transduction
        
        only genes located close to each other on the bacterial chromosome will be cotransduced
    - - Retrovirus: RNA viruses that have been integrated into host genome
        
        Reverse Transcriptase: synthesizing DNA from RNA template
        
        HIV has very error-prone reverse transcriptase which results in high mutation rates (this is why vaccines are not effective)
    - - Two Life Cycles
        
        Lytic Cycle: kills host cell
        
        Influenza: high mutation rates via recombination; three main strains A/B/C
        
        Lysogenic Cycle: the viral DNA gets integrated into the host's DNA but viral genes are not expressed.
        
        After some time, the prophage leaves the bacterial DNA and goes through the lytic cycle, creating more viruses
        
        The prophage is passed on to daughter cells during every cell division.
      - Virulent Phage: Reproduce through lytic cycle
      - Temperate Phage: inactive prophage; phage DNA integrates into bacterial chromosome
      - Gene Mapping in Phages: recombination frequency
  - - - Nonreciprocal
      - Requires an episome (F Factor)
        
        F Factor contains its own Ori and other genes for conjugation such as sex pili
        
        Types of F Factor Cells
        
        F+ Cells: donor cells that contain F factor
        
        F+ x F- cross results in two F+
        
        Hfr (high frequency strain): donor cells with F factor integrated into bacterial genome
        
        Hfr x F- cross results in one Hfr and one F-
        
        F factor nicked in the middle of initiation and can't transfer as a whole
        
        Interrupted Conjugation
        
        Hfr x F- cross used to map bacterial genes
        
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        F' Cells: donor cells with an F factor that contains parts of the genome
        
        F' x F- cross results in two F'
        
        F- Cells: recipient cells that do not contain F factor
        
        Conjugation can take place between a cell that possesses and a cell that lacks F