Download Phenotypic Effects of Mutations

LECTURE
CONNECTIONS
18 | Gene Mutations and DNA Repair
© 2009 W. H. Freeman and Company
18.1 Mutations Are Inherited Alterations in the
DNA Sequence
•
A mutation is defined as an inherited change in
genetic information; the descendents may be cells or
organisms.
•
Mutation is the source of all genetic variation, which
further provides the raw material for evolution.
•
Mutation is the source of many diseases and
disorders.
•
Useful for probing fundamental biological processes.
Categories of Mutations
• Somatic mutations
- arise in somatic tissues, which do NOT produce gametes.
- the mutation is passed on to daughter cells by mitosis.
- mutations are numerous.
- many somatic mutations have no effect on the phenotype
of the organism.
- somatic mutation that stimlulates cell division can give
rise to cancer.
• Germ-line mutations
- arise in cells that produce gametes.
- germ-line mutation can be passed to future generations.
Types of Gene Mutations
(based on their molecular nature)
• Base substitutions: the alteration of a single nucleotide in
the DNA
• Transition
• Transversion: purine is replaced by pyrimidine or viceversa.
• Insertions and deletions
• Frameshift mutations: changes in the reading frame
• In-frame insertions and deletions: a trinucleotide is added
or removed from the DNA
Concept Check 1
Which of the following changes is a transition base
substitution?
a.
b.
c.
d.
Adenine is replaced by thymine.
Cytosine is replaced by adenine.
Guanine is replaced by adenine.
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: a base substitution that results in a
different aa in the protein
• Nonsense mutation: changes a sense codon into a non-sense
codon
• Silent mutation: specify the same aa
• Neutral mutation: alters the aa sequence but does not change
its function
Phenotypic Effects of Mutations
• Loss-of-function mutations: cause the complete or partial
absence of normal protein function
• Gain-of-function mutations: produces an entirely new trait or
it causes a trait to appear in an appropriate tissue or at an
inappropriate time in development.
• Conditional mutations: are expressed only under certain
conditions.
• Lethal mutations: cause premature death.
Phenotypic Effects of Mutations
• Suppressor mutation: a mutation that hides or suppresses
the effect of another mutation, so the individual is a double
mutant with a phenotype of an unmutated wild type.
• Intragenic: is in the same gene as that containing the
mutation being suppressed
• Intergenic: occurs in a gene other than the one bearing
the original mutation.
Phenotypic Effects of Mutations
• Mutation rate
- bacterial genes: 1 to 100 mutations per 10 billion
cells
- most eukaryotes genes: 1 to 10 mutations per
million gametes
- spontaneous rates of mutation vary among species,
and genes.
Table 18.3
18.2 Mutations Are Potentially Caused by a
Number of Different Natural and
Unnatural Factors
•
Mutations result from both internal and external
factors.
•
Those that are a result of natural changes in DNA
structure are termed spontaneous mutations,
whereas those that result from changes caused
by environmental chemicals or radiation are
induced mutations.
Spontaneous Replication Errors
• Caused by mispairing through wobble
The original incorporated error leads to a
replication error, which creates a
permanent mutation.
Spontaneous Replication Errors
• Strand slippage: occurs when one nucleotide forms a loop
Spontaneous Replication Errors
• Unequal crossing over: misaligned pairing can cause
unequal crossing over, which results in one DNA molecule
with an insertion and the other with a deletion.
Spontaneous Chemical Changes
• Depurination: loss of purine base
• Deamination: loss of an amino group (NH2) from a base
Chemically Induced Mutations
• Any environmental agent that significantly increases the
rate of mutation above the spontaneous rate is called a
mutagen.
• Base analogs: chemicals with structures similar to that
of any of the four standard bases of DNA.
- DNA polymerase cannot distinguish these analogs from
the standard bases; so, if base analogs are present during
replication, they may be incorporated into newly synthesized
DNA molecules.
Normally, 5-bromouracil pairs with adenine just as
thymine does, but it occasionally mispairs with
guanine.
Chemically Induced Mutations
• Alkylating agents: donate alkyl group such as methyl
(CH3) and ethyl (CH3-CH2) groups to nucleotide bases.
• Ehtylmethylsulfonate EMS
• Mustard gas
• Deamination: can be spontaneous or be induced by
chemical agents.
- nitrous acid deaminates cytosine creating uracil
Chemically Induced Mutations
• Hydroxylamine: add hydroxyl group to cytosine
• 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.
Radiation
• Pyrimidine dimer: two thymine bases block replication.
• SOS system in bacteria: SOS system allows bacteria
cells to by pass the replication block with a mutation-prone
pathway.