GENETICS A Conceptual Approach FIFTH EDITION GENETICS A Conceptual Approach FIFTH EDITION Benjamin A. Pierce CHAPTER 18 Gene Mutations and DNA Repair © 2014 W. H. Freeman and Company

18.1 Mutations Are Inherited Alterations in the DNA Sequence The Importance of Mutations Categories of Mutations Types of Genetic Mutations Phenotypic Effects of Mutations Suppressor Mutations

The Importance of Mutations Mutations: sustainer of life and cause of great suffering Source of all genetic variation, which further provides the raw material for evolution Source of many diseases and disorders Useful for probing fundamental biological processes

Categories of Mutations Somatic mutations Germ-line mutations Gene vs. chromosomal mutations

Types of Gene Mutations (based on their molecular nature) Base substitutions Transition Transversion Insertions and deletions Frameshift mutations In-frame insertions and deletions Expanding nucleotide repeats Increase in the number of a copies of a set of nucleotides

Concept Check 1 Which of the following changes is a transition base substitution? a.Adenine is replaced by thymine. b.Cytosine is replaced by adenine. c.Guanine is replaced by adenine. d.Three nucleotide pairs are inserted into DNA.

Concept Check 1 Which of the following changes is a transition base substitution? a.Adenine is replaced by thymine. b.Cytosine is replaced by adenine. c.Guanine is replaced by adenine. d.Three nucleotide pairs are inserted into DNA.

Phenotypic Effects of Mutations Forward mutation: wild type  mutant type Reverse mutation: mutant type  wild type Missense mutation: amino acid  different amino acid Nonsense mutation: sense codon  nonsense codon Silent mutation: codon  synonymous codon Neutral mutation: no change in function

Phenotypic Effects of Mutations Loss-of-function mutations Gain-of-function mutations Conditional mutation Lethal mutation

Suppressor Mutations Suppressor mutation: a mutation that hides or suppresses the effect of another mutation Intragenic Intergenic

Mutation Rates Factors affecting mutation rates Variation in mutation rates Adaptive mutations

Factors Affecting Mutation Rates Frequency with which a change takes place in DNA The probability that when a change takes place, that change will be repaired The probability that a mutation will be detected

Adaptive Mutation Genetic variation critical for evolutionary change that brings about adaptation to new environments Stressful conditions, where adaptation might be necessary to survive, induces increased mutation in bacteria

18.2 Mutations Are Potentially Caused by a Number of Different Factors Spontaneous replication errors Spontaneous chemical changes Chemically induced mutations Radiation

Spontaneous Replication Errors Tautomeric shifts Mispairing due to other structures Incorporation errors and replication errors Causes of deletion and insertions Strand slippage Unequal crossing over

Spontaneous Chemical Changes Depurination: loss of purine Deamination: loss of an amino group

Chemically Induced Mutations Mutagen Base analogs

Chemically Induced Mutations Alkylating agents: donate alkyl group Ethylmethylsulfonate EMS Mustard gas Deamination: nitrous acid Hydroxylamine: add hydroxyl group

Chemically Induced Mutations Oxidative reaction: superoxide radicals Hydrogen peroxide Intercalating agents: proflavin, acridine orange, and ethidium bromide

Concept Check 2 Base analogs are mutagenic because of which characteristic? a.They produce changes in DNA polymerase that cause it to malfunction. b.They distort the structure of DNA. c.They are similar in structure to the normal bases. d.They chemically modify the normal bases.

Concept Check 2 Base analogs are mutagenic because of which characteristic? a.They produce changes in DNA polymerase that cause it to malfunction. b.They distort the structure of DNA. c.They are similar in structure to the normal bases. d.They chemically modify the normal bases.

Radiation Radiation greatly increases mutation rates in all organisms Pyrimidine dimer: two thymine bases block replication. SOS system in bacteria: SOS system allows bacteria cells to bypass the replication block with a mutation-prone pathway.

18.3 Mutations Are the Focus of Intense Study by Geneticists Detecting Mutations with the Ames Test Radiation Exposure in Humans

18.4 Transposable Elements Cause Mutations Transposable elements: sequences that can move about the genome Transposition: movement of the transposons Features: Flanking direct repeats Terminal inverted repeats

18.4 Transposable Elements Cause Mutations Transposons cause mutations by: Inserting into another gene Promoting DNA rearrangements Examples: Approximately half of spontaneous mutations in Drosophila Human genetic diseases The color of grapes

Transposable Elements in Bacteria DNA transposons constitute two major groups: Insertion sequences Composite transposons

Transposable Elements in Eukaryotes Two primary groups: −Similar to transposable elements in bacteria short inverted repeats −P elements in Drosophila −Ac and Ds elements −Retrotransposons Ty elements in yeast Copia elements in Drosophila Alu sequences in humans

18.5 A Number of Pathways Repair Changes in DNA Mismatch Repair Direct Repair Base-Excision Repair Nucleotide-Excision Repair

Concept Check 3 Mismatch repair in bacteria distinguishes between old and new strands of DNA on the basis of __________. a.differences in base composition of the two strands b.modification of histone proteins c.base analogs on the new strand d.methyl groups on the old strand

Concept Check 3 Mismatch repair in bacteria distinguishes between old and new strands of DNA on the basis of __________. a.differences in base composition of the two strands b.modification of histone proteins c.base analogs on the new strand d.methyl groups on the old strand

18.5 A Number of Pathways Repair Changes in DNA Repair of Double-Strand Breaks Translesion DNA Polymerases Genetics Diseases and Faulty DNA Repair