Home reading part
How DNA as genetic materials was established
Basic properties of DNA,including structure and components
(also summarized in next slide)
DNA Replication
DNA transcription
RNA translation
How DNA recombination is achieved?
Gene Conversion,one allele is converted to
another
Mutations are the results of DNA changes
Hydrolysis
UV and other radiation caused backbone alteration
Oxidation
Repair of UV damage,excision repair
Defective excision
repair causes UV
sensitivity
Various kinds of mutations
Various causes of mutations
Spontaneous
Mutagen induced
Factors for Variation of mutation rates
Organisms
Gene size
Susceptibility of gene to
functional disruption
Gene sequence
Lauria-Debruck’s experiment shows
that mutations happen pre-selection by
chance and are genetic
(or genetic mutation is random,not selection
induced)
DNA replication generates low level of mutations
DNA replication is also an source of mutation
In vitro DNA replication mutation rate 10(-6),without
proofreading,10(-4)
In vivo polymerase complex helps 10 fold,repair
system helps another 100 fold and mutation rate
lowered to 10(-9),How does repair system recognize
parental and daughter strand?
Other causes of spontaneous mutation
Unequal crossing-over
Transposition
Variation to red-green perception is often the
cause of unequal crossing-over
Various kind of mutagens
Point mutations and how they affect proteins
TYPES OF POINT MUTATIONS
Transition,A:T base pair to G:C base pair and it’s
reverse
TAG TAC ACC CCA GCT
ATC ATG TGG GGT CGA
TAG TAC GCC CCA GCU
ATC ATG CGG GGT CGA
A purine:pyrimidine
pair replaces a
purine:pyrimidine
pair
Transversion,A:T pair to a C:G pair and it’s reverse
TAG TAC ACC CCA GCT
ATC ATG TGG GGT CGA
TAG TAC CCC CCA GCT
ATC ATG GGG GGT CGA
A purine:pyrimidine
pair replaces a
pyrimidine:purine
pair
Missense mutations,change one amino acid
to another amino acid
TAG TAC ACC CCA GCT
ATC ATG TGG GGT CGA
met-tyr-thr-pro-ala
TAG TAC GCC CCA GCT
ATC ATG CGG GGT CGA
met-tyr-ala-pro-ala
Both produce wild-type proteins products
Nonsense mutation,change of a codon for
an amino acid to a stop codon:
TAG TAC ACC CAA GCT
ATC ATG TGG GTT CGA
TAG TAC ACC TAA GCT
ATC ATG TGG ATT CGA
met-tyr-thr-gln-ala met-tyr-thr
Frameshift mutation,change the reading
frame so that all amino acids translated after
the mutation are different.
TCT CAA AAA TTT ACG
AGA GTT TTT AAA TGC
TCT CAA GAA ATT TAC G
AGA GTT CTT TAA ATG C
SER-GLN-LYS-PHE-THR SER-GLN-GLU-ILE-TYR
..Or it can also produce a termination
met ILE stop TRUNCATED* PROTEIN
Frameshift,deletion or insertion of 1 or 2 basesi 1 or 2 ba
AUG AUG AUG AUG AUG AUG etc
met met met met met met etc,WILD-TYPE PROTEIN
WILD-TYPE GENE
AUG AUA UGA UGA UGA UGA etc MUTANT GENE
remove this base
* consequence of mutation varies depending on actual mutation
Example of how a mutation can give a
frameshift
Suppressor mutations,a second site
mutation nullifies the first mutation
Example,using genetics to decode metabolic pathways
A special genetic example,human triple repeat diseases
Fragile X
Correlate genotype with phenotype
Phenotypic Terms describing genetic mutations
Null
Hypormorphic
Hypermorphic
Neomorphic
Dominant negative
Half of T locus protein is not enough to make
normal tail (haploinsufficient)
A multiple-subunit complex disrupted by one
mutation,dominant negative in kinky mice
Antennapedia,an example of neomorphic
How DNA as genetic materials was established
Basic properties of DNA,including structure and components
(also summarized in next slide)
DNA Replication
DNA transcription
RNA translation
How DNA recombination is achieved?
Gene Conversion,one allele is converted to
another
Mutations are the results of DNA changes
Hydrolysis
UV and other radiation caused backbone alteration
Oxidation
Repair of UV damage,excision repair
Defective excision
repair causes UV
sensitivity
Various kinds of mutations
Various causes of mutations
Spontaneous
Mutagen induced
Factors for Variation of mutation rates
Organisms
Gene size
Susceptibility of gene to
functional disruption
Gene sequence
Lauria-Debruck’s experiment shows
that mutations happen pre-selection by
chance and are genetic
(or genetic mutation is random,not selection
induced)
DNA replication generates low level of mutations
DNA replication is also an source of mutation
In vitro DNA replication mutation rate 10(-6),without
proofreading,10(-4)
In vivo polymerase complex helps 10 fold,repair
system helps another 100 fold and mutation rate
lowered to 10(-9),How does repair system recognize
parental and daughter strand?
Other causes of spontaneous mutation
Unequal crossing-over
Transposition
Variation to red-green perception is often the
cause of unequal crossing-over
Various kind of mutagens
Point mutations and how they affect proteins
TYPES OF POINT MUTATIONS
Transition,A:T base pair to G:C base pair and it’s
reverse
TAG TAC ACC CCA GCT
ATC ATG TGG GGT CGA
TAG TAC GCC CCA GCU
ATC ATG CGG GGT CGA
A purine:pyrimidine
pair replaces a
purine:pyrimidine
pair
Transversion,A:T pair to a C:G pair and it’s reverse
TAG TAC ACC CCA GCT
ATC ATG TGG GGT CGA
TAG TAC CCC CCA GCT
ATC ATG GGG GGT CGA
A purine:pyrimidine
pair replaces a
pyrimidine:purine
pair
Missense mutations,change one amino acid
to another amino acid
TAG TAC ACC CCA GCT
ATC ATG TGG GGT CGA
met-tyr-thr-pro-ala
TAG TAC GCC CCA GCT
ATC ATG CGG GGT CGA
met-tyr-ala-pro-ala
Both produce wild-type proteins products
Nonsense mutation,change of a codon for
an amino acid to a stop codon:
TAG TAC ACC CAA GCT
ATC ATG TGG GTT CGA
TAG TAC ACC TAA GCT
ATC ATG TGG ATT CGA
met-tyr-thr-gln-ala met-tyr-thr
Frameshift mutation,change the reading
frame so that all amino acids translated after
the mutation are different.
TCT CAA AAA TTT ACG
AGA GTT TTT AAA TGC
TCT CAA GAA ATT TAC G
AGA GTT CTT TAA ATG C
SER-GLN-LYS-PHE-THR SER-GLN-GLU-ILE-TYR
..Or it can also produce a termination
met ILE stop TRUNCATED* PROTEIN
Frameshift,deletion or insertion of 1 or 2 basesi 1 or 2 ba
AUG AUG AUG AUG AUG AUG etc
met met met met met met etc,WILD-TYPE PROTEIN
WILD-TYPE GENE
AUG AUA UGA UGA UGA UGA etc MUTANT GENE
remove this base
* consequence of mutation varies depending on actual mutation
Example of how a mutation can give a
frameshift
Suppressor mutations,a second site
mutation nullifies the first mutation
Example,using genetics to decode metabolic pathways
A special genetic example,human triple repeat diseases
Fragile X
Correlate genotype with phenotype
Phenotypic Terms describing genetic mutations
Null
Hypormorphic
Hypermorphic
Neomorphic
Dominant negative
Half of T locus protein is not enough to make
normal tail (haploinsufficient)
A multiple-subunit complex disrupted by one
mutation,dominant negative in kinky mice
Antennapedia,an example of neomorphic
