SBI 4U
Protein Synthesis
Mutations
 A mutation results when the genetic message of DNA is altered.
Effects of Mutations
Mutations
Positive (useful)
Large size of the human brain
Negative (harmful)
No Effect (neutral)
Cystic fibrosis
Causes of Mutations
Mutagenic Agents
 Agents that cause mutations.
 These include:
 Radiation (UV, X-rays)
 Temperature extremes
 Exposure to chemicals (pesticides)
Types of Mutations:
1. Point Mutations
2. Chromosomal Mutations
Point Mutations:
 May occur at a certain point in the base sequence and only involve one base pair
 Point mutations include the following…
1. Substitution Mutations
SBI 4U
Protein Synthesis
2. Frameshift Mutations
 Occurs when one or more base pairs are deleted or added, thus all of the codons from that
point will code for a different amino acid.
 Insertion of Nucleotides
o One nucleotide is inserted in the
DNA sequence
Ex. Deletion of Nucleotides
o One or two nucleotides are removed from the
DNA sequence
E.g. One strand of DNA:
TACCGAAAGTGGATG
mRNA:
amino acid sequence:
altered mRNA:
new amino acid sequence:
Point mutations can lead to the following outcomes:
Silent Mutations
 Have no effect on the operation of the cell (do not change the amino acid sequence)
 Usually occurs in the noncoding regions of DNA
SBI 4U
Protein Synthesis
 Why are they silent?
o Introns are cut out of the mRNA transcript during transcription, thus mutations never
surfaces.
o Genetic code has a redundancy in nature (Ex. UUU and UUC both code for
phenylalanine
Missense Mutations
 Occurs when a change in the base sequence of DNA alters a codon, therefore a different
amino acid is placed in the protein sequence.
 E.g. sickle cell anemia
Nonsense Mutations
 Arises when a change in the DNA sequence causes a stop codon to replace a codon
specifying an amino acid
 Causes translation to stop short of the end of the full mRNA.
 Therefore, only the part of the protein that precedes the stop codon is produced (the
fragment may be digested by cell proteases)
 Are often lethal to the cell
Chromosomal Mutations
Translocation
 Part of one chromosome is transferred to a nonhomologous chromosome.
 Some fragments of DNA are constantly on the move. These
fragments are called transposable elements or “jumping
genes” and can move from one location to another in the
genome.
 Cancer (Part of chromosome 14 exchanges places with a
Inversion
part of chromosome 8)
Leukemia
is associated
with translocation
 o
Alters
the position
and sequence
of the
genes so that gene order is reversed
 This can alter gene activity
Deletion
 Loss of a chromosome part
 These pieces are actually genes, and with them go
the information required to make vital proteins.
 Cri-du-chat (The loss of a portion of chromosome
5 causes an abnormally developed larynx; makes
the affected infant’s cry sound like the meowing
of a cat)
Duplication
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Protein Synthesis
 When a gene sequence is in excess of the normal
amount
 Fragile X syndrome (Form of mental retardation,
resulting from repeats that may block expression
of a gene on the X chromosome)
MUTATION REPAIR MECHANISMS
DIRECT REPAIR / PROOFREADING DURING REPLICATION
 During DNA replication occurs, an incorrect base may be added to the growing
polynucleotide chain. DNA Polymerase I performs a proofreading function.
 When a mispairing of bases occur during the replication process, then the enzyme will
remove the improperly placed base and try again. (Helicase, DNA ligase and other
proteins also play a role in this mechanism
MISMATCH REPAIR
 If a mispairing of bases occurred during DNA replication and ‘Proofreading’ wasn’t
effective at correcting this error, then mismatch repair will take place.
 Proteins will excise the mismatched base and DNA polymerase will add the correct
bases.
EXCISION REPAIR
 During the life of a cell, DNA may become damaged due to hazards such as high-energy
radiation, chemicals that induce mutations, and random spontaneous chemical reactions.
 Therefore, the cell will rely on excision repair, where certain enzymes will ‘inspect’ the
cell’s DNA.
 When they find mispaired bases, chemically modified bases or points at which one strand
has more bases than the other, these enzymes cut the defective strand.
 Other enzymes will cut away at the adjacent bases and DNA polymerase and DNA ligase
synthesize and seal up a new piece to replace the excised one.
Homework:
p. 263 #1-9