Mutation

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Mutation Rapair
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Mutation

• ?????????????????????? Genes
• ????????? genes ?????????? (Alternative forms)
• ?????????????????????????? genes
  ?????????????????
• ?? - ??????? Phenotype ??????????????
• - ???? Biodiversity
• - ???????? ??????????????????

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Types of Mutation ?? Molecular Genetics

• I. Mutation ????? DNA sequence
• II. Mutation ????? Gene
• III. Reversion Effect ??? Mutation

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• I. Mutation ????? DNA sequence
• 1. Point Mutation
• 2. Insertion
• 3. Deletion
• 4. Inversion

• II. Mutation ????? Gene
• 1. Silent mutation
• 2. Missense
• mutation
• 3. Nonsense mutation
• 4. Frameshift mutation

III. Reversion Effect ??? Mutation 1
Back mutation 2. Second site reversion 3.
Suppression
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I. Mutation ??????????DNA(DNA sequence)
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Bases ?? Nucleic Acids
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CH3
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1. Point Mutations

• mutation ????????? 1 nucleotide ???????
  nucleotide
• ??????????????
• Transition ??? ????????????? base ?????????????
• purine to purine (A --gt G) ????
• pyrimidine to pyrimidine (T--gt C)
• Transversion ??? ????????????? base ?????????
• purine to pyrimidine (A --gt T)
• pyrimidine to purine (G --gt C)

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Point mutation
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2. Insertion

• Insertion ??? ????????? base pair ?? DNA

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3. Deletion

• Deletion ??? ?????? base pair ?????? DNA

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4. Inversion

• ????????????????? DNA duplex ?????????????????????
  ??????????????????????????????

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• Mutation ??????????????????? DNA sequence
• Point mutation
• Insertion / Deletion
• Inversion

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II. Mutation ????? Gene

• Mutation ?????? Intergenic region ??????? effect
• Mutation ?????? Coding region ???? effect

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1. Silent mutation

• ????????? point mutation ???????????? 3 ??? codon
  ????????????????????? (wobble) ??? genetic code
  ??????????????????? amino acid sequence ??? gene
  product --gt ?????? mutant phenotype
• Mutation ????? intron

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Silent Mutation
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2. Missense mutation

• ???? Point mutation 1 base ????????????????????
  codon --gt ??????? amino acid
• ?????????????? ?????????? 2 ???? 3 ??? cocdon
• ???????????????????????????? 3 (wobble)
• ???????????????? mutant phenotype ??????? amino
  acid sequence

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Missense Mutation
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3. Nonsense mutation

• Point mutation ?????????? codon ??????????? stop
  codon
• ????? gene ??? (truncated gene) --gt polypepttide
  ??????????????? carboxyl ????????????????????????
  protein ?????
• ????????????? mutant phenotype

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Nonsense Mutation
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4. Frameshift mutation

• ???? Insertion ???? deletion ???? base pairs ????
  ??????????? codon (reading frame)
• ??????????? mutation ????????????????
• ????????????? mutant phenotype

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Frameshift Mutation
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III. Reversion Effect ??? Mutation
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III. Reversion Effect ??? Mutation

• Mutant ??? ?????????? wild-type phenotype ?????
  Second mutation
• Second mutation ????? restore nucleotide sequence
  ???????? ??? DNA
• Back mutation ??? point, insertion ???
• deletion mutation
• Second site mutation (Forward mutation)
• Suppression mutation

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1. Back mutation
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2. Second site mutation

• Mutation ?????? 2 ?? gene ??????? restore
  original phenotype ?????? restore original DNA
  sequence
• ????
• Mutation ??????1 ???? missense mutation ??? DNA
• Mutation ?????? 2 ??????? codon ???????? missense
  mutation ??? mRNA --gt ??? gene product ??????
  origin ??? DNA sequence ?????????????

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3. Suppression mutation

• Mutation ?????? 2 ?????? gene
• ??????? anticodon ??????? reverse ????
• suppress stop codon mutant (nonsenese mutation)

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Suppression mutation
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????????? mutation
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Causes of Mutations

• 1. Spontaneous Mutations
• 2. Chemical Mutations
• 3. Radiation-induced Mutations
• Mutagens ??? chemical agents ????
• physical agents ???????????? mutation
• Mutagenesis ??? ??????? mutation

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1. Spontaneous Mutation
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1. Spontaneous Mutation

• mutation ??????? ??????? replication
• ?? bacterial cell ??????? ? 1 cell ?? 108 cell
  divisions
• ???? rate ??????????? ???????????? random
• ????????????????????? DNA replication ??????????
  proofreading function ??? replicating enzymes
• Spontaneous mutation ?????????????????
• Replication mechinary
• Tautomeric shift ??? Base
• Frameshift ??????? replication

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1.1 Replication machinery

• E.coli mutant strains ?? unfaithful replication
  ???????? Mutators
• Gene ??? DNA Polymerase encode ??? mutant
  subunits --gt mismatch repair ??? proofreading
  ???????? replication
• Rate mutation ??? mutator ?????????????? mutator
  ?????????? environment ?????

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1.2 Tautomeric shift ??? base

• Base ??????????????????? DNA ????? 2
  form/Tautomer
• Tautomers ??? structural isomer ?????
  ?????????????????????? ??? ???????????????????????
  
• ??????? ?? DNA ????? base ?? form ?????
• ?????????? form ??? base ???????? Tautomerization
  ???? Tautomeric shift
• Purine Pyrimidine
• A amino --gt imino T keto --gt enol
• G keto --gt enol C amino --gt imino

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Common Rare
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Tautomers ??? Base ?? DNA

• Base pairing Base pairing
• ???? ???????
• T keto A amino T enol G keto
• T keto G enol
• C amino G keto C imino A
  amino
• C amino A imino

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??????????? mutation ??? tautomers
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1.3 Frameshift mutation

• ??????? DNA replication ?? insertion/deletion
• ????? reading frame ??? codons
  ????????????????????? mutation
• ??? mutant protein

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Frameshift mutation
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2. Chemical - Induced Mutation
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2. Chemical Mutagenesis

• Mutation ??? chemicals ??? radiation
  ???????????? spontaneous mutation
• Chemicals ????????????????? mutation ???? induced
  mutation
• Chemicals ???????????? Mutagens
• Chemical mutagens 2 ?????????
• Mutagenic ??? replicating DNA
• Mutagenic ??? replicating ??? nonreplicating DNA
• Chemical mutagens ???????????????? (potent) 5
  ?????

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• Chemical Name Common Name
• I. Alkylating agents
• Di-(2-chloroethyl) sulfide Mustard gas or
  sulfur mustard
• Di-(2-chloroethyl) methylamine Nitrogen mustard
• Ethylmethane sulfonate EMS
• Ethylethane sulfonate EES
• II. Base analogs
• 5-Bromouracil 5-BU
• 2-Aminopurine 2-AP
• III. Acridines
• 2,8-Diamino acrdine Proflavin
• IV. Deaminating agents
• Nitrous acid -
• V. Hydroxylating agent
• Hydroxylamine HA

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I. Alkylation

• ?????? Methyl CH3 ???? Ethyl CH2 groups
  ??????? base ??? DNA
• ???????????? base pairing
• Alkylation ??????????????
• Adenine ?????? alkyl group ??? N3 ??? base
• Guanine ?????? alkyl group ??? N7 ??? base

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Alkylation
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II. Base Analog

• Base analog ?? ??????????????
• normal base ??? ??????? DNA ??? ????
• 5-bromouracil BU ???
• 2-aminopurine AP
• ????? mispairing ??? ???? mutation ???????
  replication

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Base analog
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III. Intercalation

• Positively charged molecules ?????????????????????
  ?????? DNA ?????????????? base pairs ??? DNA
• Proflavin, Acridine orange, Ethidium bromide ???
  related compounds
• ????? DNA ????, ????????????? (conformation)
  ?????
• Acridine-induced mutation ??????? replication ???
  insertion ???? deletion 1 - 3 base pairs --gt
  frameshift --gt gene product ?????? function

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IV. Hydroxylation

• Hydroxylamine (NH2OH) ????????? transition
• G C --gt A T
• Amino group ??? Cytosine C
• ??? hydroxylated --gt ??? Hydroxylamine-C ?? base
  pair ??? Adenine A
• ????????? transition ??? G C --gt A T
• Revert mutation ?????????? Nitrous acid ???? base
  analog

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Hydroxylation
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3. Radiation - Induced Mutation
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3. Radiation-induced Mutation

• ????? ????????????????????????????????????
  visible light
• Radiation ????????
• Inonizing radiation X-ray, gamma ray, cosmic
  ray
• Nonionizing radiation ultraviolet light

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Spectrum ??????
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Ionizing radiation

• High energy ??????????????????????????????
• ?????????????????????? ???????? ??? nuclear
  reactor
• high energy ????? atoms ???? H2O ????? atoms
  ????? electrons ??? -gt atom ???????? positively
  charged free radicals ???? ions
• ionize H2O ??? ? DNA ??? free radicals
• ???????? free radical ????? O- ?? reactive ???
• Ions ?????????????????????? --gt ????? electrons
  ????????? --gt ions ?????????

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• ???????????????????????????? ?????????
• ????????? --gt point mutation ??????????
  chromosome structure
• base change
• single strand break
• double stand break ??? chromosome break
  ???????????????? repair ???
• ionizing radiation ??????????? mutagen ???????
  clastogen
• X rays, alpha rays, beta rays, gamma rays, ???
  cosmic rays

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Nonionizing radiation

• Low energy ???? ionizing radiation ????
  ultraviolet rays
• ???????????????????? ???? ??????? --gt skin cancer
• UV ????????????? electrons ??? ??????? --gt
  electron excitation --gt atom ?????????????? --gt
  ????? DNA
• UV ????? pyrimidine bases ??????????????? DNA
  strand ???????? ???????????? ??? dimers ??? 2
  bases
• ?????????????????? T ??? T ??? T-T dimer

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DNA pol. Enzyme ??? base ?????? TT ??????
??????? base ????? random ????????????? mutation
???? replication
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????????? DNA mutation ??? UV ??????????????
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4. Heat

• ???? environmental mutagen ??????????????
• Heat ??? bond ???????
• purine ??? sugar ???
• apurinic site??????
• 10,000 sites ??? 1 cell ?????? ????

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• DNA Repair