Anda di halaman 1dari 58

Benjamin A.

Pierce

GENETICS ESSENTIALS
Concepts and Connections
SECOND EDITION

CHAPTER 13
Gene Mutations, Transposable
Elements, and DNA Repair
© 2013 W. H. Freeman and Company
OUTLINE

• Mutations Are Inherited Alterations in the DNA Sequence

• Mutations Are Potentially Caused by a Number of Different


Natural and Unnatural Factors

• Transposable Elements Are Mobile DNA Sequences


Capable of Inducing Mutations

• A Number of Pathways Repair Changes in DNA.


•tinman gene
•Nkx2.5
MUTATIONS ARE INHERITED
ALTERATIONS IN THE DNA SEQUENCE
• The Importance of Mutations

• Categories of Mutations

• Types of Gene Mutations

• Phenotypic Effects of Mutations

• Suppressor Mutations
THE IMPORTANCE OF MUTATIONS

• 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
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
• Usually recessive

• Gain-of-function mutations
• Usually dominant

• Conditional mutations
• Require specific conditions

• Lethal mutations
SUPPRESSOR MUTATIONS

• Suppressor mutation: a mutation that hides or


suppresses the effect of another mutation
•Intragenic
•Intergenic
SUPPRESSOR MUTATIONS

• Intragenic
SUPPRESSOR MUTATIONS

• 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
MUTATIONS ARE POTENTIALLY CAUSED BY A NUMBER
OF DIFFERENT NATURAL AND UNNATURAL FACTORS

Spontaneous and Induced

• 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 REPLICATION ERRORS

• Tautomeric shifts

• Mispairing due
to other
structures
• Wobble pairing
SPONTANEOUS REPLICATION ERRORS

• Incorporation errors and replication errors


SPONTANEOUS REPLICATION ERRORS

• Causes of deletion and insertions


• Strand slippage
SPONTANEOUS REPLICATION ERRORS

• Causes of deletion and insertions


• Unequal crossing over
SPONTANEOUS CHEMICAL CHANGES

• Depurination: loss of purine

• Deamination: loss of an amino group


Depurination: loss of purine
SPONTANEOUS CHEMICAL CHANGES

• 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
CHEMICALLY INDUCED MUTATIONS

• Intercalating agents: proflavin, acridine


orange, ethidium bromide, and dioxin
RADIATION

• 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.
MUTATIONS ARE THE FOCUS OF INTENSE
STUDY BY GENETICISTS

•Detecting Mutations with the Ames Test

•Radiation Exposure in Humans


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
TRANSPOSABLE ELEMENTS ARE MOBILE DNA
SEQUENCES CAPABLE OF INDUCING MUTATIONS

• General characteristics of transposable elements:


• Flanking direct repeats
• Terminal inverted repeats
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
TRANSPOSITION

The mutagenic effects of transposition:


TRANSPOSITION

Movement of transposon from one location to


another
• DNA transposons

• Retrotransposons

• Replicative transposons
• New copy is introduced on the new site, old copy remains on the
original site

• Nonreplicative Transposons
• Excises from old site and inserts in a new one (no copy increase)
A NUMBER OF PATHWAYS REPAIR
CHANGES IN DNA

• Mismatch Repair

• Direct Repair

• Base-excision Repair

• Nucleotide-excision Repair
A NUMBER OF PATHWAYS REPAIR
CHANGES IN DNA

Mismatch
Repair
A NUMBER OF PATHWAYS REPAIR
CHANGES IN DNA

• Direct Repair
A NUMBER OF PATHWAYS REPAIR
CHANGES IN DNA

• Base-excision Repair
DNA glycosylases
Uracil glycosylase

• Nucleotide-excision Repair
Removes bulky DNA lesions (pyrimidine dimers)
A NUMBER OF PATHWAYS REPAIR
CHANGES IN DNA

Genetics diseases and faulty DNA repair


•Xeroderma pigmentosum

•Hereditary non-polyposis colon cancer (HNPCC)

Anda mungkin juga menyukai