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Ch. 16
Part 3: Mutations
Mutations
• Unpredictable change in the
genetic material
– Gene Mutation: change in
structure of a DNA molecule
that produces a different
allele of a gene
– Chromosomal mutation
(ABERRATION): changes in
the structure or number of
chromosomes in an organism
• Give rise to new alleles
• Causes:
– Random
– Environmental factors
(increase chances)
• Ionizing radiation
• UV Radiation
• Chemicals
MUTAGEN!
Gene Mutations
• 3 Main types
– Point Mutation
• Base Substitutions
– May lead to silent
mutation (mutation with
no apparent affect on
organism)
– Frameshift Mutation
(significant effect)
• Base addition
(insertion)
• Base deletion (deletion)
Base Substitution
 Replacement of one base
or nucleotide with
another
 Usually do not change
amino acid
 Sometimes causes a
change in the protein
made
 Silent Mutation
 When a substitution does
not cause a change in the
protein expressed by a
gene
 Remember some codons
represent the same
amino acid
 Example: GAA and GAG
both code for Glu
• Point Mutation
A point mutation is a simple change in one base of the
gene sequence. This is equivalent to changing one
letter in a sentence, such as this example, where we
change the 'c' in cat to an 'h':
Original:
The fat cat ate the wee rat.
Point Mutation: The fat hat ate the wee rat.
Insertion or Deletion
 Nucleotide is removed or added
 More disastrous
 mRNA is read as triplet codes
 Adding/removing bases changes these three letter
codes
 Codons downstream from insertion/deletion will be
regrouped and probably code for a non-working
protein
 Result: FRAMESHIFT MUTATION
 Shift the “reading” frame of the genetic message
•
•
Frameshift
mutation
The fat cat ate the wee rat.
Original:
Frame Shift: The fat caa tet hew eer at.
Sickle Cell Anemia
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Sickle cell anemia
1/500 African Americans have the disorder
Co-dominant allele
Causes blockages in blood vessels, preventing oxygen from
getting to other cells and tissues
• Beneficial in central and east Africa because it helped
destroy malaria
– If you had SCA, your body would destroy the sickle cells to
protect itself and in the process, destroy the malaria parasite as
well
DNA and Sickle Cell Anemia
• Review hemoglobin
– 2 alpha chains
– 2 beta chain
HbA allele: allele for normal B-globin polypeptide
HbS allele: allele for normal B-globin polypeptide
• Sickle Cell Anemia
– Inherited blood disorder
HbAHbA : Normal
HbAHbS : Normal but carrier
HbSHbS: sickle cell anemia
• BASE SUBSTITUTION Mutation to DNA sequence that codes for beta
chains
– One DNA nucleotide is replaced with a different nucleotide
• Normal amino acid sequence for beta chain:
– VAL-HIS-LEU-THR-PRO-GLU-GLU-LYS– HbA allele (normal hemoglobin allele)
– DNA triplet code for Glu is CTT
• Mutated amino acid sequence for beta chain:
– VAL-HIS-LEU-THR-PRO-VAL-GLU-LYS– HbS allele (sickle cell allele)
– DNA triplet code for CTT is changed to CAT, which no longer codes for Glu, but
instead Valine
Effects of Sickle Cell Mutation
• Glutamic acid
– Found on outside of hemoglobin
– Hydrophilic aa
– Interacts with water molecules, makes
hemoglobin soluble (good!)
• Valine
– Hydrophobic aa
– Does not interact with water, makes
hemoglobin less soluble (BAD!)
• When abnormal hemoglobin is in area
of LOW oxygen concentration, they
stick together because the outside is
now hydrophobic
• Abnormal hemoglobins form long
chains of insoluble fibers
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–
–
–
These pull the red blood cells that contain the abnormal
hemoglobin inwards and out of shape (become sickle
shaped instead of round)
Sickled RBC cannot move easily through blood
Get stuck in capillaries
Possibly fatal
Albinism
• Show relationship between gene, enzyme, and
phenotype
• Albinism melanin (dark pigment) totally or
partially missing from eyes, skin, and hair
– Causes:
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Pale blue/pink irises
Pale skin
Pale hair
Red pupils
Poor vision
Jerky movements
Inability to absorb light (protection)
• Genetic Cause:
– Mutation at several LOCI
– AUTOSOMAL RECESSIVE disorder
• Must get TWO recessive alleles to have disorder
• 1 in 17000 births
– SEX-LINKED version of disorder
• Affects only eyes, not skin
• TYROSINASE an oxidase enzyme
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2 copper atoms in active site that bind to oxygen
Transmembrane protein
In membranes of large organelles in melanocytes
called melanosomes
Most of protein, including active site in in
melanosome
Also found in plants
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Enzyme reacts with air (causes blackening of potato)
Enzyme TYROSINASE converts amino acid tyrosine
into DOPA
DOPA is the converted to dopaquinone which is
then converted into Melanin
Melanin:
– dark brown to black pigment occurring in the
hair, skin, and iris of the eye
– responsible for tanning of skin exposed to
sunlight
In Albinism:
– Mutation of gene results in inactive or absent
TYROSINASE
– Without TYROSINASE, first two steps of
conversion process cannot occur
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No DOPA
No dopaquinone
No melanin
Huntington’s Disease (HD)
• Autosomal Dominant
Disorder
– Most people with
disorder are
heterozygous
– 1 in 2 chance of
passing it off to
children
• Neurological disorder
• Causes involuntary
movements (chorea)
and mental
deterioration
• Age on onset is
variable
Huntington’s Disease (HD)
• Caused by mutation
– Unstable segment in a gene
on chromosome 4 that codes
for protein HUNTINGTIN
• Protein regularly interacts
with proteins found only in
the brain
• Altered huntingtin is most
disruptive to nerve cells,
even though it is found
throughout the body
– Normal gene made of
small number of repeats of
the triplet of bases CAG
– Mutated gene contain
larger number of repeats of
CAG triplet
• STUTTER repeats of triplet
• More stutters = earlier age
in which condition appears