MutatioMutationsns

Introduction• Every normal cell carries a

full complement of genetic material

• A mutation can occur in: – a somatic (body) cell (aren’t passed to

offspring)

– a germinal/gametes(reproductive) cell – can be transmitted to offspring

Introduction• 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 another T at the beginning?T hes unw ash otb utt heo ldm and idn otg eth ish

at.

Mutations...not all are bad!• mutations are random changes in

genetic material• rare events• most mutations that are detectable

are detrimental• some mutations provide variation,

allowing for adaptation to the environment (can be favorable)

• some mutations cannot be detected

Types of Mutations

Silent mutation: – does not result in a change in the amino

acid sequence of the protein, – due to the redundancy of the genetic

code – or a change in the code on the introns.

Eg: The A.A. Phe is coded for by UUU and UUC… if U gets swapped for C on the mRNA strand the mutation will have no effect. Phe will still be coded for!

Missense mutation: – a mutation that results in the single

substitution of one amino acid in the protein.

– E g. sickle cell anemia.– Only affects one base pair on the DNA

or one codon of mRNA. – Can be called a base pair substitution

in this case.

Sickle Cell Anemia

Blood smear (normal)Image Credit: http://lifesci.rutgers.edu/~babiarz/

Sickle cell anemiaImage Credit: http://explore.ecb.org/

Nonsense mutation: – a mutation that converts a codon for an

amino acid into a stop codon (usually lethal to the cell).

– Also called a chain termination mutation.

– AAC – Codes for Asn but if changed to UAA it is now a stop codon

– UGA, UAA and UAG are the stop codons!

Frame shift mutation: – occurs when the reading frame is

changed.– Base pair deletion (one is missing) or

base pair insertion (one is added). – Changes the remainder of the code.

Point Mutation: • The previous examples are point

mutations.• They involve one base pair! • http://www.youtube.com/watch?

v=kp0esidDr-c&feature=related

Chromosomal mutation:

– shape change or missing piece of chromosome;

– can result in inactivation of the entire gene

Translocation mutation: – occurs when groups of base

pairs are relocated from one area of the genome to another,

– usually between two nonhomologous chromosomes.

– Results in a fusion protein (two unrelated gene sequences being transcribed together)

Inversion: – chromosomal segment

reverses its orientation. – Gene control is affected.

• AUG UUU UUG CCU

• UCC UUG UUU GUA

Some examples!!!

DNA

mRNA

Polypeptide

Normal geneGGTCTCCTCACGCCA

↓CCAGAGGAGUGCGGU

Codons ↓

Pro-Glu-Glu-Cys-GlyAmino acids

Addition:TAG CAT GAG

becomesTTA GCA TGA G

Mutations: Additions

Mutations: Additions

Normal geneGGTCTCCTCACGCCA

↓CCAGAGGAGUGCGGU

Codons ↓

Pro-Glu-Glu-Cys-GlyAmino acids

Addition mutationGGTGCTCCTCACGCCA

↓CCACGAGGAGUGCGGU

↓

Pro-Arg-Gly-Val-Arg

A frame shift mutation

© 2010 Paul Billiet ODWS

Mutations: Deletions

Deletion:

TAG CAT GAGBecomes

TGC ATG AG

A

Mutations: Deletions

Normal geneGGTCTCCTCACGCCA

↓CCAGAGGAGUGCGGU

Codons ↓

Pro-Glu-Glu-Cys-GlyAmino acids

Deletion mutationGGTC/CCTCACGCCA

↓CCAGGGAGUGCGGU

↓

Pro-Gly-Ser-Ala-Val

A frame shift mutation

Mutations: Substitutions

Substitution: TAG CAT GAG

BecomesTCG CAT GAG

Similar Pro with one different A.A

Mutations: Substitutions

Substitution mutationGGTCACCTCACGCCA

↓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 geneGGTCTCCTCACGCCA

↓CCAGAGGAGUGCGGU

Codons ↓

Pro-Glu-Glu-Cys-GlyAmino acids

The genetic code is degenerate/redundantA mutation can have no effect on the phenotype

Only when:Mutation/change is in the third base of a codon

often have no effect.

No changeNormal gene

GGTCTCCTCACGCCA↓

CCAGAGGAGUGCGGU Codons

↓Pro-Glu-Glu-Cys-Gly

Amino acids

Substitution mutationGGTCTTCTCACGCCA

↓CCAGAAGAGUGCGGU

↓Pro-Glu-Glu-Cys-Gly

DisasterNormal gene

GGTCTCCTCACGCCA↓

CCAGAGGAGUGCGGU Codons

↓Pro-Glu-Glu-Cys-Gly

Amino acids

Substitution mutationGGTCTCCTCACTCCA

↓CCAGAAGAGUGAGGU

↓Pro-Glu-Glu-STOP

What Causes Mutations?• Spontaneous mutations

– occur under normal conditions. – May involve mispairing during replication

• Induced mutation– caused by mutagenic agents – chemical

agent or radiation– Examples: (X-rays, formaldehyde,

toluene, UV…)

Mistakes in DNA Replication

• DNA polymerase: 1 mistake per every 100,000 nucleotides

• With 6 billion base pairs → 120,000 mistakes in every cell division

Fixing Mistakes• DNA repair (DNA

polymerase)→ Proofreading (during

replication – fixes 99% of the errors)

→ Mismatch repair (after replication)

Fixing Mistakes• UV damage fixed by:→ Photorepair (removal of

thymine dimers)→ Nucleotide excision repair

( removal of damaged or incorrect base)

The End !!!

• p266 #12 & 13• A great site for review!• http://

learn.genetics.utah.edu