Protein Synthesis and Mutation
•
Gene Regulation in Prokaryotes
•
Mutation(Permanent, heritable DNA changes)
•
•
Point mutation (base substitutions)
•
Missense mutation
•
Nonsense mutation (premature stop)
•
Silent mutation
Insertions/deletions
•
•
Frameshift mutation
•
Dramatic change in amino acids
•
Run-ons, premature stops (nonsense mut.)
The Creation of Mutation (mutagenesis)
•
Spontaneous mutation
•
•
•
Occurs in DNA replication (1 in 109 bp)
Chemical mutagens
•
Base pair changers (nitrous acid)
•
Base analogues (e.g.. 5 bromouracil)
•
Frameshift mutagens (aflatoxin, benzpyrene)
Radiation
•
X rays, gamma rays break DNA, bases
•
UV light causes knots in DNA strand
Proteins are made by translation of genetic instructions by a ribosome. Mutations in the genetic instructions usually
changes the resultant protein with deleterious effects.
Genes in Prokaryotes Are Grouped Together and Regulated Together
Inducible operon of genes (normally “off”)
Used in “rainy day” gene sets like for
lactose utilization
Repressible operon of genes (normally “on”)
Used to regulate genes that are used all the time,
like amino acid making genes
Mutation: Some Definitions
• A heritable change in the genetic material
• Mutations may be neutral, beneficial, or harmful
• Mutagen: Agent that causes mutations
• Spontaneous mutations: Occur in the absence of a
mutagen
Mutation: Base Substitution (Point Mutations)
G
G
C
C
Glu
(a) Silent mutation
(d) Run-on mutation
Regulation of Bacterial Gene Expression
•
Steps in Translation of mRNA
•
•
Initiation, Elongation, Termination
Mutation(Permanent, heritable DNA changes)
•
•
Point mutation (base substitutions)
•
Missense mutation
•
Nonsense mutation (premature stop)
•
Silent mutation
Insertions/deletions
•
•
Frameshift mutation
•
Dramatic change in amino acids
•
Run-ons, premature stops (nonsense mut.)
The Creation of Mutation (mutagenesis)
•
Spontaneous mutation
•
•
•
Occurs in DNA replication (1 in 109 bp)
Chemical mutagens
•
Base pair changers (nitrous acid)
•
Base analogues (e.g.. 5 bromouracil)
•
Frameshift mutagens (aflatoxin, benzpyrene)
Radiation
•
X rays, gamma rays break DNA, bases
•
UV light causes knots in DNA strand
Proteins are made by translation of genetic instructions by a ribosome. Mutations in the genetic instructions usually
changes the resultant protein with deleterious effects.
Mutation: Insertions and Deletions
THEBIGCATATETHERAT
THEBIGCBATATETHERAT
Figure 8.17a, d
Summary of Mutation Types
Run-on mutation
Stop codon lost so
protein is extra long
(can also produce
nonsense and run-ons)
Protein Synthesis and Mutation
•
Steps in Translation of mRNA
•
•
Initiation, Elongation, Termination
Mutation(Permanent, heritable DNA changes)
•
•
Point mutation (base substitutions)
•
Missense mutation
•
Nonsense mutation (premature stop)
•
Silent mutation
Insertions/deletions
•
•
Frameshift mutation
•
Dramatic change in amino acids
•
Run-ons, premature stops (nonsense mut.)
The Creation of Mutation (mutagenesis)
•
Spontaneous mutation
•
•
•
Occurs in DNA replication (1 in 109 bp)
Chemical mutagens
•
Base pair changers (nitrous acid)
•
Base analogues (e.g.. 5 bromouracil)
•
Frameshift mutagens (aflatoxin, benzpyrene)
Radiation
•
X rays, gamma rays break DNA, bases
•
UV light causes knots in DNA strand
Proteins are made by translation of genetic instructions by a ribosome. Mutations in the genetic instructions usually
changes the resultant protein with deleterious effects.
Spontaneous and Induced Mutation
• Spontaneous mutation rate = 1 in 109 (a billion)
replicated base pairs or 1 in 106 ( a million) replicated
genes. Mistakes occur during DNA Replication just
before cell division. This is natural error rate of DNA
polymerase.
• Mutagens increase mistakes to to 10–5 (100
thousand) or 10–3 ( a thousand) per replicated gene
Chemical Mutagens
Base pair altering chemicals
(base modifiers) deaminators
like nitrous acid,
nitrosoguanidine, or alkylating
agents like cytoxan
cytoxan
Nitrous acid
Base analogues “mimic”
certain bases but pair with
others - E.g. 5-fluorouracil,
cytarabine
Incorporated as a “T”
cytarabine
Acts like a “C”
Chemical Frameshift Mutagens Intercalate into DNA
Carboplatin
(anti-cancer drug)
Benzpyrene in
cigarette smoke
Aflatoxin from
Aspergillus fungus
growing on corn
AT
GC
TA
GC
CG
AT
GC
TA
GC
CG
AT
GC
CG
TA
GC
CG
Daunarubicin
(anti-cancer drug)
Bleomycin (anti-cancer
drug produced by
Streptomyces)
Protein Synthesis and Mutation
•
Steps in Translation of mRNA
•
•
Initiation, Elongation, Termination
Mutation(Permanent, heritable DNA changes)
•
•
Point mutation (base substitutions)
•
Missense mutation
•
Nonsense mutation (premature stop)
•
Silent mutation
Insertions/deletions
•
•
Frameshift mutation
•
Dramatic change in amino acids
•
Run-ons, premature stops (nonsense mut.)
The Creation of Mutation (mutagenesis)
•
Spontaneous mutation
•
•
•
Occurs in DNA replication (1 in 109 bp)
Chemical mutagens
•
Base pair changers (nitrous acid)
•
Base analogues (e.g.. 5 bromouracil)
•
Frameshift mutagens (aflatoxin, benzpyrene)
Radiation
•
X rays, gamma rays break DNA, bases
•
UV light causes knots in DNA strand
Proteins are made by translation of genetic instructions by a ribosome. Mutations in the genetic instructions usually
changes the resultant protein with deleterious effects.
Mutation: Ionizing Radiation
• Ionizing radiation (X rays, gamma rays, UV light)
causes the formation of ions that can react with
nucleotides and the deoxyribose-phosphate backbone.
• Nucleotide excision repairs mutations
X-rays and Gamma Rays Cause Breaks in DNA
Ionizing Radiation: UV
• UV radiation
causes thymine
dimers, which block
replication.
• Light-repair
separates thymine
dimers
• Sometimes the
“repair job”
introduces the
wrong nucleotide,
leading to a point
mutation.
Figure 8.20
Mismatch and SOS/”Light” Repair: Error Prone
RecA
Protein Synthesis and Mutation
•
Steps in Translation of mRNA
•
•
Initiation, Elongation, Termination
Mutation(Permanent, heritable DNA changes)
•
•
Point mutation (base substitutions)
•
Missense mutation
•
Nonsense mutation (premature stop)
•
Silent mutation
Insertions/deletions
•
•
Frameshift mutation
•
Dramatic change in amino acids
•
Run-ons, premature stops (nonsense mut.)
The Creation of Mutation (mutagenesis)
•
Spontaneous mutation
•
•
•
Occurs in DNA replication (1 in 109 bp)
Chemical mutagens
•
Base pair changers (nitrous acid)
•
Base analogues (e.g.. 5 bromouracil)
•
Frameshift mutagens (aflatoxin, benzpyrene)
Radiation
•
X rays, gamma rays break DNA, bases
•
UV light causes knots in DNA strand
Proteins are made by translation of genetic instructions by a ribosome. Mutations in the genetic instructions usually
changes the resultant protein with deleterious effects.