genetic mutations good, bad or neutral?. mutations inheritable errors made in dna during replication...
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Genetic Mutations
Good, bad or neutral?
Mutations
Inheritable errors made in DNA during replication
3 broad groups:BeneficialDeleteriousNeutral
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 Mutations1) 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 replicationCan 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 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.
Cancer
Categories of Mutations
1. Point mutationsMutations at a specific base pair on the
genome
2. Chromosomal mutationsOne 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:SubstitutionInsertion or deletionInversionhttp://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: SubstitutionsSubstitution mutation
GGTCACCTCACGCCA
↓
CCAGUGGAGUGCGGU
↓
Pro-Arg-Glu-Cys-Gly
Substitutions will only affect a single codonTheir 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)
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
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 changeNormal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Substitution mutation
GGTCTTCTCACGCCA
↓
CCAGAAGAGUGCGGU
↓
Pro-Glu-Glu-Cys-Gly
© 2010 Paul Billiet ODWS
DisasterNormal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Substitution mutation
GGTCTCCTCACTCCA
↓
CCAGAAGAGUGAGGU
↓
Pro-Glu-Glu-STOP
© 2010 Paul Billiet ODWS
Addition:
TAG CAT GAG
becomes
TTA GCA TGA G
Mutations: Insertions
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
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Addition mutation
GGTGCTCCTCACGCCA
↓
CCACGAGGAGUGCGGU
↓
Pro-Arg-Gly-Val-Arg
A frame shift mutation
© 2010 Paul Billiet ODWS
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
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Deletion mutation
GGTC/CCTCACGCCA
↓
CCAGGGAGUGCGGU
↓
Pro-Gly-Ser-Ala-Val
A frame shift mutation
© 2010 Paul Billiet ODWS
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
Blood smear (normal)Image Credit: http://lifesci.rutgers.edu/~babiarz/
Sickle cell anemiaImage Credit: http://explore.ecb.org/
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
SubstitutionsFrame shift Mutations
Cross over Mutations
Missense Mutations
Nonsense Mutations
Deletion Insertion Inversion TranslocationSegment Deletion/
Segment Duplication