Download 5.6 Mutations

Genetic Mutations

Good, bad or neutral?
Mutations
Inheritable errors made in DNA during
replication
 3 broad groups:

 Beneficial
 Deleterious
 Neutral

Most mutations are neutral, either because
they occur in introns, or because of the
redundancy inherent in our genome
Mutations


Mistakes in the DNA sequence can alter the
function of proteins produced
Diploid organisms have two copies of each gene
so error may be masked in the phenotype
Causes of Mutations
1) Spontaneous mutations (copying errors)
2) Induced mutations (exposure to mutagens)
Spontaneous Mutations
 Occur
under normal conditions.
 Caused by errors during DNA replication that
are go uncorrected
 May involve mispairing during replication
 Can also be caused by errors made during
crossover in meiosis
Induced Mutations:

2 kinds of mutagens:
 Physical
mutagens physically damage DNA
strands (X-rays, UV light)
 Chemical mutagens alter the molecular
structure of DNA without damaging it physically
(carbon monoxide, ethidium bromide)

Note: mutagens that also cause cancer are
called carcinogens
Environmental Causes of
Mutation
Physical Mutagens

For example, radiation
Causes of Genetic Mutations
Cancer
 Cancer is a genetic disease because it is
always a result of a mutation in the genetic
sequence.
 Mutations result in oncogenes - genes that
control cell growth and division.
Categories of Mutations
1. Point mutations
 Mutations
at a specific base pair on the
genome
2. Chromosomal mutations
 One
DNA fragment is moved from one site on
the genome to another
Types of DNA Replication
Errors:
Small scale, point mutations effect only a
small group of base pairs:
 Substitution
 Insertion or deletion
 Inversion

http://www.youtube.com/watch?v=kp0esidDr-c
Analogy:
Split this sentence into codons!
Thesunwashotbuttheoldmandidnotgethishat.
 It should look like this...
The sun was hot but the old man did not get
his hat.
 What if we substituted one of the letters?
Substitution Analogy:

The sun was hot but the old man did not get
his hat.

The son was hot but the old man did not get
his hat.

The bun was hot but the old man did not get
his hat.
Mutations: Substitutions
Substitution:
TAG CAT GAG
Becomes
TCG CAT GAG
= Similar protein with one different A.A
Mutations: Substitutions
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Substitution mutation
GGTCACCTCACGCCA
↓
CCAGUGGAGUGCGGU
↓
Pro-Arg-Glu-Cys-Gly
Substitutions will only affect a single codon
Their effects may not be serious unless they affect an amino acid that is
essential for the structure and function of the finished protein molecule (e.g.
sickle cell anaemia)
The genetic code is degenerate
A mutation to have no effect on the phenotype
Changes in the third base of a codon often have
no effect.
(The wobble hypothesis)
© 2010 Paul Billiet ODWS
No change
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
© 2010 Paul Billiet ODWS
Substitution mutation
GGTCTTCTCACGCCA
↓
CCAGAAGAGUGCGGU
↓
Pro-Glu-Glu-Cys-Gly
Disaster
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
© 2010 Paul Billiet ODWS
Substitution mutation
GGTCTCCTCACTCCA
↓
CCAGAAGAGUGAGGU
↓
Pro-Glu-Glu-STOP
Mutations: Insertions
Addition:
TAG CAT GAG
becomes
TTA GCA TGA G
Analogy:
Split this into codons!
Thesunwashotbuttheoldmandidnotgethishat.
 It should look like this...
The sun was hot but the old man did not get
his hat.


What if we added an extra letter?
Analogy: Insertion
Split this sentence into codons:
Thesunwashotbuttheoldmandidnotgethishatt.
Does this sentence still make sense?
 The sun was hot but the old man did not get
his hat t.

Analogy: Insertion
Split this sentence into codons:
Theesunwashotbuttheoldmandidnotgethishat.
Does this sentence still make sense?
The esu nwa sho tbu tth eol dma ndi dno tge
thi sha t.

Mutations: Additions
A frame shift mutation
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
© 2010 Paul Billiet ODWS
Addition mutation
GGTGCTCCTCACGCCA
↓
CCACGAGGAGUGCGGU
↓
Pro-Arg-Gly-Val-Arg
Mutations: Deletions
Deletion:
TAG CAT GAG
Becomes
TGC ATG AG
A
Analogy:
Split this into codons!
Thesunwashotbuttheoldmandidnotgethishat.
 It should look like this...
The sun was hot but the old man did not get
his hat.


What if we removed a random letter?
Analogy: Insertion
Split this sentence into codons:
Thesunwashotbuttheoldmandidnotgethisht.
Does this sentence still make sense?
 The sun was hot but the old man did not get
his ht.

Analogy: Insertion
Split this sentence into codons:
Heesunwashotbuttheoldmandidnotgethishat.
Does this sentence still make sense?
Hes unw ash otb utt heo ldm and idn otg eth
ish at.

Mutations: Deletions
A frame shift mutation
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
© 2010 Paul Billiet ODWS
Deletion mutation
GGTC/CCTCACGCCA
↓
CCAGGGAGUGCGGU
↓
Pro-Gly-Ser-Ala-Val
Inversion:
 Two
adjoining base
pairs or entire
chromosomal segment
reverses its
orientation.
 Gene control is
affected.

AUG UUU UUG CCU

UCC UUG UUU GUA
Inversion
The reversal of a segment of DNA within a
chromosome.
 No gain or loss
of genetic information.
 A gene may be
disrupted.

Translocation
Characterized by relocation of groups of
base pairs from one place in the genome
to another.
 “Jumping genes” are called Transposable
elements.

Translocation



The transfer of a
fragment of DNA from
one site in the genome
to another location.
Usually occurs
between two
nonhomologous
chromosomes.
Result is a fusion
protein with an altered
function
Transposable Elements
Also known as “jumping genes”.
 Certain fragments of DNA consistently
move from one location to another.
 If they are added to a coding region of a
gene, it will leave it inactive.

Effects of DNA Mutations
Single point mutations in the population
cause genetic variations in individuals
called SNPs (single nucleotide
polymorphisms)
 They are very common and variable in
non-coding portions of the genome
 Why?

Effects of DNA Mutations
As you can see, the type of error can have
very different effects on protein production.
Mutations can be categorized into 4 groups:
1. Silent mutations
2. Missense mutations
3. Nonsense mutations
4. Frame shift mutations
Examples: Regular DNA Strand

Genetic code as inherited from parents:
1) Silent Mutations

Due to the wobble effect, this base pair
change has no effect on the amino acid
produced
Silent Mutation
Does not result in a phenotypic change.
 Primarily occurs in the introns.
 Could be due to redundancy of genetic
code e.g. phenylalanine coded for by UUU
and UUC…a change in the 3rd base does
not change the amino acid.

2) Missense Mutations
Point mutation produces a different amino
acid in the polypeptide chain
 Can be neutral, harmful or beneficial

Substitutions:
Missense Mutation
A single substitution of one base in a
codon, resulting in a different amino acid.
 E.g., Sickle cell anemia.

Sickle Cell Anaemia
Sickle cell anemia
Image Credit: http://explore.ecb.org/
Blood smear (normal)
Image Credit: http://lifesci.rutgers.edu/~babiarz/
3) Nonsense Mutations
Point mutation produces a premature
STOP codon rather an amino acid
 Protein produced is usually non-functional

4) Frameshift Mutations
Insertion or deletion shifts the entire reading
frame of the codons, usually resulting in
different amino acids being incorporated
from that point onwards.
 Eg. Tay sachs

Frameshift Mutation
Causes changes in the reading frame.
 Caused by an insertion:



Addition of one or more base pairs in a DNA
sequence.
Caused by a deletion:

Removal of one or more base pairs in a DNA
sequence.
Question:
Why would the deletion
of 3 nucleotides be
better then 2?
Review of Mutation Effects:
Mutations
Substitutions
Missense
Mutations
Nonsense
Mutations
Frame shift
Mutations
Deletion
Insertion
Cross over
Mutations
Inversion
Segment Deletion/
TranslocationSegment Duplication