Download Suppressor mutation

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
CHAPTER 13 OUTLINE
• 13.1 Mutations Are Inherited Alterations in the DNA
Sequence, 340
• 13.2 Mutations Are Potentially Caused by a Number of
Different Natural and Unnatural Factors, 348
• 13.3 Transposable Elements Are Mobile DNA Sequences
Capable of Inducing Mutations, 355
• 13.4 A Number of Pathways Repair Changes in DNA, 358
•tinman gene
•Nkx2.5
13.1 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
TYPES OF GENE MUTATIONS (BASED ON
THEIR MOLECULAR NATURE)
• Expanding nucleotide repeats
• Increase in the number of 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
13.2 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
• 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
SPONTANEOUS CHEMICAL CHANGES
• Deamination: loss of an amino group
CHEMICALLY INDUCED MUTATIONS
• Mutagen
• Base analogs
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.
13.3 TRANSPOSABLE ELEMENTS ARE MOBILE DNA
SEQUENCES CAPABLE OF INDUCING MUTATIONS
• General characteristics of transposable elements:
• Flanking direct repeats
• Terminal inverted repeats
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)
TRANSPOSITION
• The mutagenic effects of transposition:
18.4 A NUMBER OF PATHWAYS REPAIR
CHANGES IN DNA
• Mismatch Repair
• Direct Repair
• Base-excision Repair
• Nucleotide-excision Repair
18.4 A NUMBER OF PATHWAYS REPAIR
CHANGES IN DNA
• Mismatch Repair
18.4 A NUMBER OF PATHWAYS REPAIR
CHANGES IN DNA
• Direct Repair
18.4 A NUMBER OF PATHWAYS REPAIR
CHANGES IN DNA
• Base-excision Repair
•DNA glycosylases
•Uracil glycosylase
• Nucleotide-excision Repair
•Removes bulky DNA lesions (pyrimidine dimers)
18.4 A NUMBER OF PATHWAYS REPAIR
CHANGES IN DNA
• Genetics diseases and faulty DNA repair
•Xeroderma pigmentosum
•Hereditary non-polyposis colon cancer (HNPCC)