SlideShare a Scribd company logo
1 of 26
Download to read offline
Mutation
• A change in the DNA molecule
• Process which produces changes in the DNA
  that may be inherited.
Mutagenicity
• = mutagenic activity of a compound
• Mutagenic compound = a compound that
  causes mutation
• Mutations in certain genes could lead to
  malignant transformation of the cell.
• Many mutagens are supposed to be
  carcinogenic.
Mutations Defined


1. A mutation is a change in a DNA base-pair or a
   chromosome.
    a. Somatic mutations affect only the individual in which they arise.
    b. Germ-line mutations alter gametes, affecting the next generation.
2. Mutations are quantified in two different ways:
    a. Mutation rate is the probability of a particular kind of mutation
       as a function of time (e.g., number per gene per generation).
    b. Mutation frequency is number of times a particular mutation
       occurs in proportion to the number of cells or individuals in a
       population (e.g., number per 100,000 organisms).


台大農藝系 遺傳學 601 20000            Chapter 19 slide 3
Types of Point Mutations
1.   There are two general categories of point mutations: base-pair
     substitutions and base-pair deletions or insertions.

2.   A base-pair substitution replaces 1 base-pair with another. There are
     two types (Figure 19.3):
     a. Transitions convert a purine-pyrimidine pair to the other purine-
         pyrimidine pair (e.g., AT to GC or TA to CG).
     b. Transversions convert a purine-pyrimidine pair to a pyrimidine-purine
         pair (e.g., AT to TA, or AT to CG).


3.   Base-pair substitutions in ORFs are also defined by their effect on the
     protein sequence. Effects vary from none to severe.
     a. Nonsense mutations change a codon in the ORF to a stop (nonsense)
     codon, resulting in premature termination of translation, and a
     truncated (often nonfunctional) protein (Figure 19.4).
台大農藝系 遺傳學 601 20000               Chapter 19 slide 4
Fig. 19.3a-d Types of base-pair substitution mutations




 台大農藝系 遺傳學 601 20000                                                        Chapter 19 slide 5
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
Fig. 19.3e-g Types of base-pair substitution mutations




 台大農藝系 遺傳學 601 20000                                                        Chapter 19 slide 6
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
Fig. 19.4 A nonsense mutation and its effect on translation




 台大農藝系 遺傳學 601 20000                                                        Chapter 19 slide 7
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
b. Missense mutations have a base-pair change resulting in a different mRNA
        codon, and therefore a different amino acid in the protein.
     c. Phenotypic effects may or may not occur, depending on the specific amino acid
        change.
          i. Neutral mutations change a codon in the ORF, but the resulting amino acid
             substitution produces no detectable change in the function of the protein
             (e.g., AAA to AGA substitutes arginine for lysine. The amino acids have similar
             properties, so the protein’s function may not be altered).
          ii. Silent mutations occur when the mutant codon encodes the same amino acid as
              the wild-type gene, so that no change occurs in the protein produced (e.g., AAA
              and AAG both encode lysine, so this transition would be silent).
4.   Deletions and insertions can change the reading frame of the mRNA
     downstream of the mutation, resulting in a frameshift mutation.
     Frameshift mutations result from insertions or deletions when the number of
     affected base pairs is not divisible by three.
     a. When the reading frame is shifted, incorrect amino acids are usually incorporated.
     b. Frameshifts may bring stop codons into the reading frame, creating a shortened
        protein.
     c. Frameshifts may also result in read-through of stop codons, resulting in a longer
        protein.
                                        台大農藝系 遺傳學 601 20000                          Chapter 19 slide 8
Reverse Mutations
1. Point mutations are divided into two classes based on their effect on phenotype:
    a. Forward mutations change the genotype from wild type to mutant.
    b. Reverse mutations (reversions or back mutations) change the genotype from mutant
       to wild-type or partially wild-type.
         i. A reversion to the wild-type amino acid in the affected protein is a true
            reversion.
         ii. A reversion to some other amino acid that fully or partly restores protein
             function is a partial reversion.




台大農藝系 遺傳學 601 20000                     Chapter 19 slide 9
Spontaneous and Induced Mutations


1.Most mutations are spontaneous, rather than
  induced by a mutagen.




台大農藝系 遺傳學 601 20000    Chapter 19 slide 10
Spontaneous Mutations
1. All types of point mutations can occur spontaneously, during S, G1 and
   G2 phases of the cell cycle, or by the movement of transposons.
2. The spontaneous mutation rate in eukaryotes is between 10-4-to-10-6 per
   gene per generation, and in bacteria and phages 10-5-to-10-7/
   gene/generation.
    a. Genetic constitution of the organism affects its mutation rate.
         i. In Drosophila, males and females of the same strain have similar
            mutation rates.
         ii. Flies of different strains, however, may have different mutation
            rates.
    b. Many spontaneous errors are corrected by the cellular repair
       systems, and so do not become fixed in DNA.




台大農藝系 遺傳學 601 20000             Chapter 19 slide 11
DNA Replication Errors
1. DNA replication errors can be either point mutations, or small
   insertions or deletions.
2. Base-pair substitution mutations can result from “wobble” pairing. A
   normal form of the base-pairs with an incorrect partner due to different
   spatial positioning of the atoms involved in H-bonding (Figure 19.6).
   An example is a GC-to-AT transition (Figure 19.7):
    a. During DNA replication, G could wobble pair with T, producing a GT
       pair.
    b. In the next round of replication, G and A are likely to pair
       normally, producing one progeny DNA with a GC pair, and another
       with an AT pair.
    c. GT pairs are targets for correction by proofreading during
       replication, and by other repair systems. Only mismatches uncorrected
       before the next round of replication lead to mutations.

台大農藝系 遺傳學 601 20000             Chapter 19 slide 12
Fig. 19.7 Production of a mutation as a result of a mismatch caused by wobble base
                                              pairing




 台大農藝系 遺傳學 601 20000                                                       Chapter 19 slide 13
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
3. Additions and deletions can occur spontaneously during
   replication (Figure 19.8).
    a. DNA loops out from the template strand, generally in a run of the
       same base.
    b. DNA polymerase skips the looped out bases, creating a deletion
       mutation.
    c. If DNA polymerase adds untemplated base(s), new DNA looping
       occurs, resulting in additional mutation.
    d. Insertions and deletions in structural genes generate frameshift
       mutations (especially if they are not multiples of three).


台大農藝系 遺傳學 601 20000            Chapter 19 slide 14
Fig. 19.8 Spontaneous generation of addition and deletion mutants by DNA
                                 looping-out errors during replication




 台大農藝系 遺傳學 601 20000                                                       Chapter 19 slide 15
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
Fig. 19.9 Deamination of cytosine to uracil (a); deamination of 5-methylcytosine to
                                              thymine




 台大農藝系 遺傳學 601 20000                                                       Chapter 19 slide 16
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
Induced Mutations
1. Exposure to physical mutagens plays a role in genetic research, where they are used to
   increase mutation frequencies to provide mutant organisms for study.
2. Radiation (e.g., X rays and UV) induces mutations.
     a. X rays are an example of ionizing radiation, which penetrates tissue and collides with
        molecules, knocking electrons out of orbits and creating ions.
          i. Ions can break covalent bonds, including those in the DNA sugar-phosphate backbone.
          ii. Ionizing radiation is the leading cause of human gross chromosomal mutations.
          iii. Ionizing radiation kills cells at high doses, and lower doses produce point mutations.
          iv. Ionizing radiation has a cumulative effect. A particular dose of radiation results in the
              same number of mutations whether it is received over a short or a long period of time.
     b. Ultraviolet (UV) causes photochemical changes in the DNA.
          i. UV is not energetic enough to induce ionization.
          ii. UV has lower-energy wavelengths than X rays, and so has limited penetrating power.
          iii. However, UV in the 254–260 nm range is strongly absorbed by purines and
              pyrimidines, forming abnormal chemical bonds.
                (1)A common effect is dimer formation between adjacent pyrimidines, commonly
                   thymines (designated T^T) (Figure 19.11).
                (2)C^C, C^T and T^C dimers also occur, but at lower frequency. Any pyrimidine dimer
                   can cause problems during DNA replication.
           (3)Most pyrimidine dimers are repaired, because they produce a bulge in the DNA
台大農藝系 遺傳學 601 20000 If enough are unrepaired, cell death may result.
               helix.                Chapter 19 slide 17
Fig. 19.11 Production of thymine dimers by ultraviolet light irradiation




 台大農藝系 遺傳學 601 20000                                                       Chapter 19 slide 18
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
Chemical Mutagens
1. Chemical mutagens may be naturally occurring, or synthetic. They form
   different groups based on their mechanism of action:
    a. Base analogs depend upon replication, which incorpocates a base with
       alternate states (tautomers) that allow it to base pair in alternate
       ways, depending on its state.
         i. Analogs are similar to normal nitrogen bases, and so are incorporated
            into DNA readily.
         ii. Once in the DNA, a shift in the analog’s form will cause incorrect
            base pairing during replication, leading to mutation.
         iii. 5-bromouradil (5BU) is an example. 5BU has a bromine residue
            instead of the methyl group of thymine (Figure 19.12).
               (1) Normally 5BU resembles thymine, pairs with adenine and is
                 incorporated into DNA during replication.
               (2) In its rare state, 5BU pairs only with guanine, resulting in a TA-
                 to-CG transition mutation.
               (3) If 5BU is incorporated in its rare form, the switch to its normal
                 state results in a CG-to-TA transition. Thus 5BU- induced
                 mutations may be reverted by another exposure to 5BU.
         iv. Not all base analogs are mutagens, only those that cause base- pair
            changes (e.g, AZT is a stable analog that does not shift).
台大農藝系 遺傳學 601 20000                Chapter 19 slide 19
Fig. 19.12a, b Mutagenic effects of the base analog 5-bromouracil (5BU)




 台大農藝系 遺傳學 601 20000                                                       Chapter 19 slide 20
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
Fig. 19.12c Mutagenic effects of the base analog 5-bromouracil (5BU)




 台大農藝系 遺傳學 601 20000                                                       Chapter 19 slide 21
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
b. Base-modifying agents can induce mutations at any stage of the cell cycle. They work by modifying the
    chemical structure and properties of the bases. Three types are (Figure 19.13):
      i.   Deaminating agents remove amino groups. An example is nitrous acid (HNO 2 ), which
           deaminates G, C and A.


            (1) HNO2 deaminates guanine to produce xanthine, which has the same base pairing as G. No
               mutation results.
            (2) HNO2 deaminates cytosine to produce uradil, which produces a CG-to-TA transition.
            (3) HNO2 deaminates adenine to produce hypoxanthine, which pairs with cytosine, causing an
               AT-to-GC transition.


      ii. Hydroxylating agents include hydroxylamine (NH2OH).


            (1) NH2OH specifically modifies C with a hydroxyl group (OH), so that it pairs only with A
                instead of with G.


      iii. Alkylating agents are a diverse group that add alkyl groups to bases. Usually alkylation occurs at the
                   6-oxygen of G, producing O6-allcylguanine.


            (1) An example is methylmethane sulfonate (MMS), which methylates G to produce O6-alkyl G.
            (2) O6-aIkylG pairs with T rather than C, causing GC-to-AT transitions.

                                           台大農藝系 遺傳學 601 20000                                    Chapter 19 slide 22
Fig. 19.13a Action of three base-modifying agents




 台大農藝系 遺傳學 601 20000                                                       Chapter 19 slide 23
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
Fig. 19.13b, c Action of three base-modifying agents




 台大農藝系 遺傳學 601 20000                                                       Chapter 19 slide 24
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
c. Intercalating agents insert themselves between adjacent bases in dsDNA.
      They are generally thin, plate-like hydrophobic molecules.

        i. At replication, a template that contains an intercalated agent will cause
          insertion of a random extra base.

        ii. The base-pair addition is complete after another round of
          replication, during which the intercalating agent is lost.

        iii. If an intercalating agent inserts into new DNA in place of a normal
          base, the next round of replication will result in a deletion mutation.

        iv. Point deletions and insertions in ORFs result in frameshift mutations.




台大農藝系 遺傳學 601 20000                Chapter 19 slide 25
Fig. 19.14 Intercalating mutations




 台大農藝系 遺傳學 601 20000                                                       Chapter 19 slide 26
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.

More Related Content

What's hot (20)

Dna replication eukaryotes
Dna replication eukaryotesDna replication eukaryotes
Dna replication eukaryotes
 
mutagenesis
mutagenesismutagenesis
mutagenesis
 
Cloning vectors
Cloning vectorsCloning vectors
Cloning vectors
 
Mutagen
MutagenMutagen
Mutagen
 
transduction
transductiontransduction
transduction
 
Mutation
MutationMutation
Mutation
 
DNA reparing
DNA reparingDNA reparing
DNA reparing
 
Plasmid
PlasmidPlasmid
Plasmid
 
Restriction endonucleases
Restriction endonucleasesRestriction endonucleases
Restriction endonucleases
 
Protein engineering
Protein engineeringProtein engineering
Protein engineering
 
spontaneous and induced mutations
spontaneous and induced mutationsspontaneous and induced mutations
spontaneous and induced mutations
 
Genetic organization of eukaryotes and prokaryotes
Genetic organization of eukaryotes and prokaryotes Genetic organization of eukaryotes and prokaryotes
Genetic organization of eukaryotes and prokaryotes
 
Transcription regulatory elements
Transcription regulatory elementsTranscription regulatory elements
Transcription regulatory elements
 
Genetic code
Genetic codeGenetic code
Genetic code
 
Recombination
RecombinationRecombination
Recombination
 
TRANSPOSABLE ELEMENTS
TRANSPOSABLE ELEMENTSTRANSPOSABLE ELEMENTS
TRANSPOSABLE ELEMENTS
 
Mutations
MutationsMutations
Mutations
 
Mutations
MutationsMutations
Mutations
 
Mutagens
MutagensMutagens
Mutagens
 
Gene mapping
Gene mappingGene mapping
Gene mapping
 

Similar to Mutation (20)

Mutation 120401050204-phpapp02
Mutation 120401050204-phpapp02Mutation 120401050204-phpapp02
Mutation 120401050204-phpapp02
 
ch19 supplementary mutation.ppt
ch19 supplementary mutation.pptch19 supplementary mutation.ppt
ch19 supplementary mutation.ppt
 
Chapt 08
Chapt 08Chapt 08
Chapt 08
 
Chapt 08
Chapt 08Chapt 08
Chapt 08
 
Gene mutations spontaneous and induced
Gene mutations  spontaneous and inducedGene mutations  spontaneous and induced
Gene mutations spontaneous and induced
 
Transposable elements & Transposon mutagenesis
Transposable elements & Transposon mutagenesis Transposable elements & Transposon mutagenesis
Transposable elements & Transposon mutagenesis
 
Lesson 16 mutations
Lesson 16 mutationsLesson 16 mutations
Lesson 16 mutations
 
Science10_Q3_ver4_Mod5.pdf
Science10_Q3_ver4_Mod5.pdfScience10_Q3_ver4_Mod5.pdf
Science10_Q3_ver4_Mod5.pdf
 
Mutation
MutationMutation
Mutation
 
Molecular Basis of Mutation
Molecular Basis of MutationMolecular Basis of Mutation
Molecular Basis of Mutation
 
molecular-basis-of-mutation.pdf
molecular-basis-of-mutation.pdfmolecular-basis-of-mutation.pdf
molecular-basis-of-mutation.pdf
 
Final Version-Molecular Biology II -DNA damage.pptx
Final Version-Molecular Biology II -DNA damage.pptxFinal Version-Molecular Biology II -DNA damage.pptx
Final Version-Molecular Biology II -DNA damage.pptx
 
Mutation and DNA repair mechanism
Mutation and DNA repair mechanismMutation and DNA repair mechanism
Mutation and DNA repair mechanism
 
Mutation and DNA repair.pdf
Mutation and DNA repair.pdfMutation and DNA repair.pdf
Mutation and DNA repair.pdf
 
Dna mutation
Dna mutationDna mutation
Dna mutation
 
Mutation.pptx
Mutation.pptxMutation.pptx
Mutation.pptx
 
1 12-2013
1 12-20131 12-2013
1 12-2013
 
Silent mutation
Silent mutationSilent mutation
Silent mutation
 
MUTATION.pptx
MUTATION.pptxMUTATION.pptx
MUTATION.pptx
 
mutation ppt
 mutation ppt mutation ppt
mutation ppt
 

More from ankit

Ulcers
UlcersUlcers
Ulcersankit
 
Routes of drug administration
Routes of drug administrationRoutes of drug administration
Routes of drug administrationankit
 
POLYMERASE CHAIN REACTION
POLYMERASE CHAIN REACTIONPOLYMERASE CHAIN REACTION
POLYMERASE CHAIN REACTIONankit
 
Oral hypoglycemics
Oral hypoglycemicsOral hypoglycemics
Oral hypoglycemicsankit
 
Nuclear magnetic resonance partial lecture notes
Nuclear magnetic resonance   partial lecture notesNuclear magnetic resonance   partial lecture notes
Nuclear magnetic resonance partial lecture notesankit
 
Ipr case1
Ipr case1Ipr case1
Ipr case1ankit
 
Human retroviruses
Human retroviruses Human retroviruses
Human retroviruses ankit
 
Histamine & bradykinin
Histamine & bradykininHistamine & bradykinin
Histamine & bradykininankit
 
Expression systems
Expression systemsExpression systems
Expression systemsankit
 
Chrono pharmacokinetics
Chrono pharmacokineticsChrono pharmacokinetics
Chrono pharmacokineticsankit
 
Animal models of nociception (pain)
Animal models of nociception (pain)Animal models of nociception (pain)
Animal models of nociception (pain)ankit
 
radioligand binding studies
radioligand binding studiesradioligand binding studies
radioligand binding studiesankit
 
Participation of the gabaergic system on the glutamate
Participation of the gabaergic system on the glutamateParticipation of the gabaergic system on the glutamate
Participation of the gabaergic system on the glutamateankit
 
Lectin-functionalized carboxymethylated kappa-carrageenan microparticles for ...
Lectin-functionalized carboxymethylated kappa-carrageenan microparticles for ...Lectin-functionalized carboxymethylated kappa-carrageenan microparticles for ...
Lectin-functionalized carboxymethylated kappa-carrageenan microparticles for ...ankit
 
Oral contraceptives
Oral contraceptivesOral contraceptives
Oral contraceptivesankit
 
Anti inflammatory agents used in asthma and cough suppressants
Anti inflammatory agents used in asthma and cough suppressantsAnti inflammatory agents used in asthma and cough suppressants
Anti inflammatory agents used in asthma and cough suppressantsankit
 

More from ankit (16)

Ulcers
UlcersUlcers
Ulcers
 
Routes of drug administration
Routes of drug administrationRoutes of drug administration
Routes of drug administration
 
POLYMERASE CHAIN REACTION
POLYMERASE CHAIN REACTIONPOLYMERASE CHAIN REACTION
POLYMERASE CHAIN REACTION
 
Oral hypoglycemics
Oral hypoglycemicsOral hypoglycemics
Oral hypoglycemics
 
Nuclear magnetic resonance partial lecture notes
Nuclear magnetic resonance   partial lecture notesNuclear magnetic resonance   partial lecture notes
Nuclear magnetic resonance partial lecture notes
 
Ipr case1
Ipr case1Ipr case1
Ipr case1
 
Human retroviruses
Human retroviruses Human retroviruses
Human retroviruses
 
Histamine & bradykinin
Histamine & bradykininHistamine & bradykinin
Histamine & bradykinin
 
Expression systems
Expression systemsExpression systems
Expression systems
 
Chrono pharmacokinetics
Chrono pharmacokineticsChrono pharmacokinetics
Chrono pharmacokinetics
 
Animal models of nociception (pain)
Animal models of nociception (pain)Animal models of nociception (pain)
Animal models of nociception (pain)
 
radioligand binding studies
radioligand binding studiesradioligand binding studies
radioligand binding studies
 
Participation of the gabaergic system on the glutamate
Participation of the gabaergic system on the glutamateParticipation of the gabaergic system on the glutamate
Participation of the gabaergic system on the glutamate
 
Lectin-functionalized carboxymethylated kappa-carrageenan microparticles for ...
Lectin-functionalized carboxymethylated kappa-carrageenan microparticles for ...Lectin-functionalized carboxymethylated kappa-carrageenan microparticles for ...
Lectin-functionalized carboxymethylated kappa-carrageenan microparticles for ...
 
Oral contraceptives
Oral contraceptivesOral contraceptives
Oral contraceptives
 
Anti inflammatory agents used in asthma and cough suppressants
Anti inflammatory agents used in asthma and cough suppressantsAnti inflammatory agents used in asthma and cough suppressants
Anti inflammatory agents used in asthma and cough suppressants
 

Recently uploaded

Bird eye's view on Camunda open source ecosystem
Bird eye's view on Camunda open source ecosystemBird eye's view on Camunda open source ecosystem
Bird eye's view on Camunda open source ecosystemAsko Soukka
 
Artificial Intelligence & SEO Trends for 2024
Artificial Intelligence & SEO Trends for 2024Artificial Intelligence & SEO Trends for 2024
Artificial Intelligence & SEO Trends for 2024D Cloud Solutions
 
Linked Data in Production: Moving Beyond Ontologies
Linked Data in Production: Moving Beyond OntologiesLinked Data in Production: Moving Beyond Ontologies
Linked Data in Production: Moving Beyond OntologiesDavid Newbury
 
Empowering Africa's Next Generation: The AI Leadership Blueprint
Empowering Africa's Next Generation: The AI Leadership BlueprintEmpowering Africa's Next Generation: The AI Leadership Blueprint
Empowering Africa's Next Generation: The AI Leadership BlueprintMahmoud Rabie
 
Connector Corner: Extending LLM automation use cases with UiPath GenAI connec...
Connector Corner: Extending LLM automation use cases with UiPath GenAI connec...Connector Corner: Extending LLM automation use cases with UiPath GenAI connec...
Connector Corner: Extending LLM automation use cases with UiPath GenAI connec...DianaGray10
 
Secure your environment with UiPath and CyberArk technologies - Session 1
Secure your environment with UiPath and CyberArk technologies - Session 1Secure your environment with UiPath and CyberArk technologies - Session 1
Secure your environment with UiPath and CyberArk technologies - Session 1DianaGray10
 
OpenShift Commons Paris - Choose Your Own Observability Adventure
OpenShift Commons Paris - Choose Your Own Observability AdventureOpenShift Commons Paris - Choose Your Own Observability Adventure
OpenShift Commons Paris - Choose Your Own Observability AdventureEric D. Schabell
 
Anypoint Code Builder , Google Pub sub connector and MuleSoft RPA
Anypoint Code Builder , Google Pub sub connector and MuleSoft RPAAnypoint Code Builder , Google Pub sub connector and MuleSoft RPA
Anypoint Code Builder , Google Pub sub connector and MuleSoft RPAshyamraj55
 
Computer 10: Lesson 10 - Online Crimes and Hazards
Computer 10: Lesson 10 - Online Crimes and HazardsComputer 10: Lesson 10 - Online Crimes and Hazards
Computer 10: Lesson 10 - Online Crimes and HazardsSeth Reyes
 
9 Steps For Building Winning Founding Team
9 Steps For Building Winning Founding Team9 Steps For Building Winning Founding Team
9 Steps For Building Winning Founding TeamAdam Moalla
 
Comparing Sidecar-less Service Mesh from Cilium and Istio
Comparing Sidecar-less Service Mesh from Cilium and IstioComparing Sidecar-less Service Mesh from Cilium and Istio
Comparing Sidecar-less Service Mesh from Cilium and IstioChristian Posta
 
Using IESVE for Loads, Sizing and Heat Pump Modeling to Achieve Decarbonization
Using IESVE for Loads, Sizing and Heat Pump Modeling to Achieve DecarbonizationUsing IESVE for Loads, Sizing and Heat Pump Modeling to Achieve Decarbonization
Using IESVE for Loads, Sizing and Heat Pump Modeling to Achieve DecarbonizationIES VE
 
UWB Technology for Enhanced Indoor and Outdoor Positioning in Physiological M...
UWB Technology for Enhanced Indoor and Outdoor Positioning in Physiological M...UWB Technology for Enhanced Indoor and Outdoor Positioning in Physiological M...
UWB Technology for Enhanced Indoor and Outdoor Positioning in Physiological M...UbiTrack UK
 
VoIP Service and Marketing using Odoo and Asterisk PBX
VoIP Service and Marketing using Odoo and Asterisk PBXVoIP Service and Marketing using Odoo and Asterisk PBX
VoIP Service and Marketing using Odoo and Asterisk PBXTarek Kalaji
 
UiPath Studio Web workshop series - Day 6
UiPath Studio Web workshop series - Day 6UiPath Studio Web workshop series - Day 6
UiPath Studio Web workshop series - Day 6DianaGray10
 
AI Fame Rush Review – Virtual Influencer Creation In Just Minutes
AI Fame Rush Review – Virtual Influencer Creation In Just MinutesAI Fame Rush Review – Virtual Influencer Creation In Just Minutes
AI Fame Rush Review – Virtual Influencer Creation In Just MinutesMd Hossain Ali
 
Apres-Cyber - The Data Dilemma: Bridging Offensive Operations and Machine Lea...
Apres-Cyber - The Data Dilemma: Bridging Offensive Operations and Machine Lea...Apres-Cyber - The Data Dilemma: Bridging Offensive Operations and Machine Lea...
Apres-Cyber - The Data Dilemma: Bridging Offensive Operations and Machine Lea...Will Schroeder
 
UiPath Studio Web workshop series - Day 8
UiPath Studio Web workshop series - Day 8UiPath Studio Web workshop series - Day 8
UiPath Studio Web workshop series - Day 8DianaGray10
 
activity_diagram_combine_v4_20190827.pdfactivity_diagram_combine_v4_20190827.pdf
activity_diagram_combine_v4_20190827.pdfactivity_diagram_combine_v4_20190827.pdfactivity_diagram_combine_v4_20190827.pdfactivity_diagram_combine_v4_20190827.pdf
activity_diagram_combine_v4_20190827.pdfactivity_diagram_combine_v4_20190827.pdfJamie (Taka) Wang
 

Recently uploaded (20)

20230104 - machine vision
20230104 - machine vision20230104 - machine vision
20230104 - machine vision
 
Bird eye's view on Camunda open source ecosystem
Bird eye's view on Camunda open source ecosystemBird eye's view on Camunda open source ecosystem
Bird eye's view on Camunda open source ecosystem
 
Artificial Intelligence & SEO Trends for 2024
Artificial Intelligence & SEO Trends for 2024Artificial Intelligence & SEO Trends for 2024
Artificial Intelligence & SEO Trends for 2024
 
Linked Data in Production: Moving Beyond Ontologies
Linked Data in Production: Moving Beyond OntologiesLinked Data in Production: Moving Beyond Ontologies
Linked Data in Production: Moving Beyond Ontologies
 
Empowering Africa's Next Generation: The AI Leadership Blueprint
Empowering Africa's Next Generation: The AI Leadership BlueprintEmpowering Africa's Next Generation: The AI Leadership Blueprint
Empowering Africa's Next Generation: The AI Leadership Blueprint
 
Connector Corner: Extending LLM automation use cases with UiPath GenAI connec...
Connector Corner: Extending LLM automation use cases with UiPath GenAI connec...Connector Corner: Extending LLM automation use cases with UiPath GenAI connec...
Connector Corner: Extending LLM automation use cases with UiPath GenAI connec...
 
Secure your environment with UiPath and CyberArk technologies - Session 1
Secure your environment with UiPath and CyberArk technologies - Session 1Secure your environment with UiPath and CyberArk technologies - Session 1
Secure your environment with UiPath and CyberArk technologies - Session 1
 
OpenShift Commons Paris - Choose Your Own Observability Adventure
OpenShift Commons Paris - Choose Your Own Observability AdventureOpenShift Commons Paris - Choose Your Own Observability Adventure
OpenShift Commons Paris - Choose Your Own Observability Adventure
 
Anypoint Code Builder , Google Pub sub connector and MuleSoft RPA
Anypoint Code Builder , Google Pub sub connector and MuleSoft RPAAnypoint Code Builder , Google Pub sub connector and MuleSoft RPA
Anypoint Code Builder , Google Pub sub connector and MuleSoft RPA
 
Computer 10: Lesson 10 - Online Crimes and Hazards
Computer 10: Lesson 10 - Online Crimes and HazardsComputer 10: Lesson 10 - Online Crimes and Hazards
Computer 10: Lesson 10 - Online Crimes and Hazards
 
9 Steps For Building Winning Founding Team
9 Steps For Building Winning Founding Team9 Steps For Building Winning Founding Team
9 Steps For Building Winning Founding Team
 
Comparing Sidecar-less Service Mesh from Cilium and Istio
Comparing Sidecar-less Service Mesh from Cilium and IstioComparing Sidecar-less Service Mesh from Cilium and Istio
Comparing Sidecar-less Service Mesh from Cilium and Istio
 
Using IESVE for Loads, Sizing and Heat Pump Modeling to Achieve Decarbonization
Using IESVE for Loads, Sizing and Heat Pump Modeling to Achieve DecarbonizationUsing IESVE for Loads, Sizing and Heat Pump Modeling to Achieve Decarbonization
Using IESVE for Loads, Sizing and Heat Pump Modeling to Achieve Decarbonization
 
UWB Technology for Enhanced Indoor and Outdoor Positioning in Physiological M...
UWB Technology for Enhanced Indoor and Outdoor Positioning in Physiological M...UWB Technology for Enhanced Indoor and Outdoor Positioning in Physiological M...
UWB Technology for Enhanced Indoor and Outdoor Positioning in Physiological M...
 
VoIP Service and Marketing using Odoo and Asterisk PBX
VoIP Service and Marketing using Odoo and Asterisk PBXVoIP Service and Marketing using Odoo and Asterisk PBX
VoIP Service and Marketing using Odoo and Asterisk PBX
 
UiPath Studio Web workshop series - Day 6
UiPath Studio Web workshop series - Day 6UiPath Studio Web workshop series - Day 6
UiPath Studio Web workshop series - Day 6
 
AI Fame Rush Review – Virtual Influencer Creation In Just Minutes
AI Fame Rush Review – Virtual Influencer Creation In Just MinutesAI Fame Rush Review – Virtual Influencer Creation In Just Minutes
AI Fame Rush Review – Virtual Influencer Creation In Just Minutes
 
Apres-Cyber - The Data Dilemma: Bridging Offensive Operations and Machine Lea...
Apres-Cyber - The Data Dilemma: Bridging Offensive Operations and Machine Lea...Apres-Cyber - The Data Dilemma: Bridging Offensive Operations and Machine Lea...
Apres-Cyber - The Data Dilemma: Bridging Offensive Operations and Machine Lea...
 
UiPath Studio Web workshop series - Day 8
UiPath Studio Web workshop series - Day 8UiPath Studio Web workshop series - Day 8
UiPath Studio Web workshop series - Day 8
 
activity_diagram_combine_v4_20190827.pdfactivity_diagram_combine_v4_20190827.pdf
activity_diagram_combine_v4_20190827.pdfactivity_diagram_combine_v4_20190827.pdfactivity_diagram_combine_v4_20190827.pdfactivity_diagram_combine_v4_20190827.pdf
activity_diagram_combine_v4_20190827.pdfactivity_diagram_combine_v4_20190827.pdf
 

Mutation

  • 1. Mutation • A change in the DNA molecule • Process which produces changes in the DNA that may be inherited.
  • 2. Mutagenicity • = mutagenic activity of a compound • Mutagenic compound = a compound that causes mutation • Mutations in certain genes could lead to malignant transformation of the cell. • Many mutagens are supposed to be carcinogenic.
  • 3. Mutations Defined 1. A mutation is a change in a DNA base-pair or a chromosome. a. Somatic mutations affect only the individual in which they arise. b. Germ-line mutations alter gametes, affecting the next generation. 2. Mutations are quantified in two different ways: a. Mutation rate is the probability of a particular kind of mutation as a function of time (e.g., number per gene per generation). b. Mutation frequency is number of times a particular mutation occurs in proportion to the number of cells or individuals in a population (e.g., number per 100,000 organisms). 台大農藝系 遺傳學 601 20000 Chapter 19 slide 3
  • 4. Types of Point Mutations 1. There are two general categories of point mutations: base-pair substitutions and base-pair deletions or insertions. 2. A base-pair substitution replaces 1 base-pair with another. There are two types (Figure 19.3): a. Transitions convert a purine-pyrimidine pair to the other purine- pyrimidine pair (e.g., AT to GC or TA to CG). b. Transversions convert a purine-pyrimidine pair to a pyrimidine-purine pair (e.g., AT to TA, or AT to CG). 3. Base-pair substitutions in ORFs are also defined by their effect on the protein sequence. Effects vary from none to severe. a. Nonsense mutations change a codon in the ORF to a stop (nonsense) codon, resulting in premature termination of translation, and a truncated (often nonfunctional) protein (Figure 19.4). 台大農藝系 遺傳學 601 20000 Chapter 19 slide 4
  • 5. Fig. 19.3a-d Types of base-pair substitution mutations 台大農藝系 遺傳學 601 20000 Chapter 19 slide 5 Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
  • 6. Fig. 19.3e-g Types of base-pair substitution mutations 台大農藝系 遺傳學 601 20000 Chapter 19 slide 6 Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
  • 7. Fig. 19.4 A nonsense mutation and its effect on translation 台大農藝系 遺傳學 601 20000 Chapter 19 slide 7 Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
  • 8. b. Missense mutations have a base-pair change resulting in a different mRNA codon, and therefore a different amino acid in the protein. c. Phenotypic effects may or may not occur, depending on the specific amino acid change. i. Neutral mutations change a codon in the ORF, but the resulting amino acid substitution produces no detectable change in the function of the protein (e.g., AAA to AGA substitutes arginine for lysine. The amino acids have similar properties, so the protein’s function may not be altered). ii. Silent mutations occur when the mutant codon encodes the same amino acid as the wild-type gene, so that no change occurs in the protein produced (e.g., AAA and AAG both encode lysine, so this transition would be silent). 4. Deletions and insertions can change the reading frame of the mRNA downstream of the mutation, resulting in a frameshift mutation. Frameshift mutations result from insertions or deletions when the number of affected base pairs is not divisible by three. a. When the reading frame is shifted, incorrect amino acids are usually incorporated. b. Frameshifts may bring stop codons into the reading frame, creating a shortened protein. c. Frameshifts may also result in read-through of stop codons, resulting in a longer protein. 台大農藝系 遺傳學 601 20000 Chapter 19 slide 8
  • 9. Reverse Mutations 1. Point mutations are divided into two classes based on their effect on phenotype: a. Forward mutations change the genotype from wild type to mutant. b. Reverse mutations (reversions or back mutations) change the genotype from mutant to wild-type or partially wild-type. i. A reversion to the wild-type amino acid in the affected protein is a true reversion. ii. A reversion to some other amino acid that fully or partly restores protein function is a partial reversion. 台大農藝系 遺傳學 601 20000 Chapter 19 slide 9
  • 10. Spontaneous and Induced Mutations 1.Most mutations are spontaneous, rather than induced by a mutagen. 台大農藝系 遺傳學 601 20000 Chapter 19 slide 10
  • 11. Spontaneous Mutations 1. All types of point mutations can occur spontaneously, during S, G1 and G2 phases of the cell cycle, or by the movement of transposons. 2. The spontaneous mutation rate in eukaryotes is between 10-4-to-10-6 per gene per generation, and in bacteria and phages 10-5-to-10-7/ gene/generation. a. Genetic constitution of the organism affects its mutation rate. i. In Drosophila, males and females of the same strain have similar mutation rates. ii. Flies of different strains, however, may have different mutation rates. b. Many spontaneous errors are corrected by the cellular repair systems, and so do not become fixed in DNA. 台大農藝系 遺傳學 601 20000 Chapter 19 slide 11
  • 12. DNA Replication Errors 1. DNA replication errors can be either point mutations, or small insertions or deletions. 2. Base-pair substitution mutations can result from “wobble” pairing. A normal form of the base-pairs with an incorrect partner due to different spatial positioning of the atoms involved in H-bonding (Figure 19.6). An example is a GC-to-AT transition (Figure 19.7): a. During DNA replication, G could wobble pair with T, producing a GT pair. b. In the next round of replication, G and A are likely to pair normally, producing one progeny DNA with a GC pair, and another with an AT pair. c. GT pairs are targets for correction by proofreading during replication, and by other repair systems. Only mismatches uncorrected before the next round of replication lead to mutations. 台大農藝系 遺傳學 601 20000 Chapter 19 slide 12
  • 13. Fig. 19.7 Production of a mutation as a result of a mismatch caused by wobble base pairing 台大農藝系 遺傳學 601 20000 Chapter 19 slide 13 Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
  • 14. 3. Additions and deletions can occur spontaneously during replication (Figure 19.8). a. DNA loops out from the template strand, generally in a run of the same base. b. DNA polymerase skips the looped out bases, creating a deletion mutation. c. If DNA polymerase adds untemplated base(s), new DNA looping occurs, resulting in additional mutation. d. Insertions and deletions in structural genes generate frameshift mutations (especially if they are not multiples of three). 台大農藝系 遺傳學 601 20000 Chapter 19 slide 14
  • 15. Fig. 19.8 Spontaneous generation of addition and deletion mutants by DNA looping-out errors during replication 台大農藝系 遺傳學 601 20000 Chapter 19 slide 15 Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
  • 16. Fig. 19.9 Deamination of cytosine to uracil (a); deamination of 5-methylcytosine to thymine 台大農藝系 遺傳學 601 20000 Chapter 19 slide 16 Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
  • 17. Induced Mutations 1. Exposure to physical mutagens plays a role in genetic research, where they are used to increase mutation frequencies to provide mutant organisms for study. 2. Radiation (e.g., X rays and UV) induces mutations. a. X rays are an example of ionizing radiation, which penetrates tissue and collides with molecules, knocking electrons out of orbits and creating ions. i. Ions can break covalent bonds, including those in the DNA sugar-phosphate backbone. ii. Ionizing radiation is the leading cause of human gross chromosomal mutations. iii. Ionizing radiation kills cells at high doses, and lower doses produce point mutations. iv. Ionizing radiation has a cumulative effect. A particular dose of radiation results in the same number of mutations whether it is received over a short or a long period of time. b. Ultraviolet (UV) causes photochemical changes in the DNA. i. UV is not energetic enough to induce ionization. ii. UV has lower-energy wavelengths than X rays, and so has limited penetrating power. iii. However, UV in the 254–260 nm range is strongly absorbed by purines and pyrimidines, forming abnormal chemical bonds. (1)A common effect is dimer formation between adjacent pyrimidines, commonly thymines (designated T^T) (Figure 19.11). (2)C^C, C^T and T^C dimers also occur, but at lower frequency. Any pyrimidine dimer can cause problems during DNA replication. (3)Most pyrimidine dimers are repaired, because they produce a bulge in the DNA 台大農藝系 遺傳學 601 20000 If enough are unrepaired, cell death may result. helix. Chapter 19 slide 17
  • 18. Fig. 19.11 Production of thymine dimers by ultraviolet light irradiation 台大農藝系 遺傳學 601 20000 Chapter 19 slide 18 Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
  • 19. Chemical Mutagens 1. Chemical mutagens may be naturally occurring, or synthetic. They form different groups based on their mechanism of action: a. Base analogs depend upon replication, which incorpocates a base with alternate states (tautomers) that allow it to base pair in alternate ways, depending on its state. i. Analogs are similar to normal nitrogen bases, and so are incorporated into DNA readily. ii. Once in the DNA, a shift in the analog’s form will cause incorrect base pairing during replication, leading to mutation. iii. 5-bromouradil (5BU) is an example. 5BU has a bromine residue instead of the methyl group of thymine (Figure 19.12). (1) Normally 5BU resembles thymine, pairs with adenine and is incorporated into DNA during replication. (2) In its rare state, 5BU pairs only with guanine, resulting in a TA- to-CG transition mutation. (3) If 5BU is incorporated in its rare form, the switch to its normal state results in a CG-to-TA transition. Thus 5BU- induced mutations may be reverted by another exposure to 5BU. iv. Not all base analogs are mutagens, only those that cause base- pair changes (e.g, AZT is a stable analog that does not shift). 台大農藝系 遺傳學 601 20000 Chapter 19 slide 19
  • 20. Fig. 19.12a, b Mutagenic effects of the base analog 5-bromouracil (5BU) 台大農藝系 遺傳學 601 20000 Chapter 19 slide 20 Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
  • 21. Fig. 19.12c Mutagenic effects of the base analog 5-bromouracil (5BU) 台大農藝系 遺傳學 601 20000 Chapter 19 slide 21 Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
  • 22. b. Base-modifying agents can induce mutations at any stage of the cell cycle. They work by modifying the chemical structure and properties of the bases. Three types are (Figure 19.13): i. Deaminating agents remove amino groups. An example is nitrous acid (HNO 2 ), which deaminates G, C and A. (1) HNO2 deaminates guanine to produce xanthine, which has the same base pairing as G. No mutation results. (2) HNO2 deaminates cytosine to produce uradil, which produces a CG-to-TA transition. (3) HNO2 deaminates adenine to produce hypoxanthine, which pairs with cytosine, causing an AT-to-GC transition. ii. Hydroxylating agents include hydroxylamine (NH2OH). (1) NH2OH specifically modifies C with a hydroxyl group (OH), so that it pairs only with A instead of with G. iii. Alkylating agents are a diverse group that add alkyl groups to bases. Usually alkylation occurs at the 6-oxygen of G, producing O6-allcylguanine. (1) An example is methylmethane sulfonate (MMS), which methylates G to produce O6-alkyl G. (2) O6-aIkylG pairs with T rather than C, causing GC-to-AT transitions. 台大農藝系 遺傳學 601 20000 Chapter 19 slide 22
  • 23. Fig. 19.13a Action of three base-modifying agents 台大農藝系 遺傳學 601 20000 Chapter 19 slide 23 Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
  • 24. Fig. 19.13b, c Action of three base-modifying agents 台大農藝系 遺傳學 601 20000 Chapter 19 slide 24 Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
  • 25. c. Intercalating agents insert themselves between adjacent bases in dsDNA. They are generally thin, plate-like hydrophobic molecules. i. At replication, a template that contains an intercalated agent will cause insertion of a random extra base. ii. The base-pair addition is complete after another round of replication, during which the intercalating agent is lost. iii. If an intercalating agent inserts into new DNA in place of a normal base, the next round of replication will result in a deletion mutation. iv. Point deletions and insertions in ORFs result in frameshift mutations. 台大農藝系 遺傳學 601 20000 Chapter 19 slide 25
  • 26. Fig. 19.14 Intercalating mutations 台大農藝系 遺傳學 601 20000 Chapter 19 slide 26 Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.