MutationsMutations

MutationMutation

Permanent changes Permanent changes or errors in a DNA or errors in a DNA sequencesequence

Copied during DNA Copied during DNA replicationreplication Therefore heritableTherefore heritable

OR may occur OR may occur during transcription during transcription to mRNA sequence to mRNA sequence

Germ Cell MutationGerm Cell Mutation

Occur in reproductive cells of an Occur in reproductive cells of an organismorganism

Will be passed on to offspringWill be passed on to offspring

Somatic Cell MutationSomatic Cell Mutation

Occurs in body cells Occurs in body cells

Side effects may be:Side effects may be: NegativeNegative PositivePositive There may be noneThere may be none

Normal hemoglobin Sickle-cell hemoglobin

Glu Val

Normal hemoglobin DNA Mutant hemoglobin DNA

mRNA mRNA

Sickle Cell Anemia Sickle Cell Anemia

CausesCauses

Exposure to mutagenic agentsExposure to mutagenic agents UV (ultraviolet) radiationUV (ultraviolet) radiation Cosmic raysCosmic rays Chemicals – e.g. pesticidesChemicals – e.g. pesticides X raysX rays

Types of MutationsTypes of Mutations

Point MutationPoint Mutation

a.k.a – Gene Mutationa.k.a – Gene Mutation Only one or a few Only one or a few

nucleotides are nucleotides are affectedaffected

ChromosomalChromosomal Affects multiple genesAffects multiple genes May affect genes on May affect genes on

separate separate chromosomeschromosomes

mRNA

Protein Met Lys Phe Gly Ala

Base substitution

Met Lys Phe Ser Ala

Replacement Replacement of one base of one base by anotherby another

AAG CCC GGC AAAAAG CCC GGC AAA AAG AAG AACC GGC AAACC GGC AAA

SubstitutionSubstitution

Possible ResultsPossible Results

Missense mutationMissense mutation Only one amino acid is changedOnly one amino acid is changed

DNADNA RNARNA Amino AcidAmino Acid

CCCCCC = = GGGGGG = = GlyGly

AACCCC = = UGGUGG = = TrpTrp

Possible ResultsPossible Results

Nonsense MutationNonsense Mutation Amino acid in middle of protein is Amino acid in middle of protein is

changed to a stop codonchanged to a stop codon Protein not complete & inactiveProtein not complete & inactive

DNADNA Amino AcidAmino AcidGTA AGT CGGGTA AGT CGG == His – Ser - AlaHis – Ser - AlaGTA AGTA ACCT CGGT CGG = = His – His – STOPSTOP - Ala - Ala

Possible ResultsPossible Results

Silent MutationSilent Mutation Amino acid is not changedAmino acid is not changed

DNADNA RNARNA Amino AcidAmino Acid

CTACTA = = GAUGAU = = AspAsp

CTCTGG = = GACGAC = = AspAsp

DeletionDeletion

Elimination of one or more base pairsElimination of one or more base pairs

AAAAGG CCC GGC AAA CCC GGC AAA

AA CCC GGC AAA AA CCC GGC AAA ← shift over← shift over

AAC CCG GCA AAAAC CCG GCA AA

Addition/InsertionAddition/Insertion

Placement of one or more base pairsPlacement of one or more base pairs

AAG CCC GGC AAAAAG CCC GGC AAA

AAG AAG AACC CGG CAA ACC CGG CAA A

Reading Frame Reading Frame

The sun was hot but the old man The sun was hot but the old man did not get his hat.did not get his hat.

Letters = base pairs (3 letters = codon)Letters = base pairs (3 letters = codon) Words = amino acidWords = amino acid Sentence = proteinSentence = protein

T hes unw ash otb utt heo ldm and T hes unw ash otb utt heo ldm and idn otg eth ish at.idn otg eth ish at.

Th esu nwa sho tbu tth eol dma ndi Th esu nwa sho tbu tth eol dma ndi dno tge thi sha t.dno tge thi sha t.

Possible ResultsPossible Results

Frameshift mutationFrameshift mutation Moves ‘reading frame’Moves ‘reading frame’

Codon = 3 basesCodon = 3 bases

Changes many amino acidsChanges many amino acids

Note:Note: May also result in a nonsense mutationMay also result in a nonsense mutation

Met Lys Leu Ala His

Nucleotide deletion

mRNA

Protein Met Lys Phe Gly Ala

Deletion MutationDeletion Mutation

Result:Result: FrameshiftFrameshift

mRNA = mRNA = GCU ACU CAA UUC

1. Translate the mRNA above.

2. Translate each mutated mRNA below.a) GCU ACU CGA UUC b) GCU ACG CAA UUCc) GCU ACU UCA AUU C

3. What was the result of each mutation?4. Which would be most harmful?

TaskTask

Page 263Page 263 Answer #2 to 7Answer #2 to 7

Omit #6(e)Omit #6(e)

For #5: list a For #5: list a maximum of 10 maximum of 10

#2 – Additions more harmful #2 – Additions more harmful than substitutions?than substitutions?

Substitution May be silent May change only one amino acid Result: minor protein change

Addition Changes reading frame Result: completely new protein

Exception If substitution resulted in a nonsense mutation

#3 – #3 – Nonsense vs. MissenseNonsense vs. Missense

Nonsense:Nonsense: Translation ends before protein is completeTranslation ends before protein is complete Protein = inactiveProtein = inactive

Missense:Missense: One amino acid changedOne amino acid changed Protein = may/may not function properlyProtein = may/may not function properly

Which is more harmful?Which is more harmful?

#4 – Causes #4 – Causes

UV radiationUV radiation Cosmic raysCosmic rays X raysX rays Chemicals – e.g. pesticidesChemicals – e.g. pesticides

#5 – Create Stop Codon#5 – Create Stop Codon

Stop codons: Stop codons: UGA, UAA, UAG UGA, UAA, UAG

Change one base to become stop codon: Change one base to become stop codon: UAU, UAC, UGU, UGC, UGG, UUA, UCA, UAU, UAC, UGU, UGC, UGG, UUA, UCA,

UUG, UCG, CGA, AGA, GGA, CAA, CAG, UUG, UCG, CGA, AGA, GGA, CAA, CAG, AAA, AAG, GAA, GAGAAA, AAG, GAA, GAG

#6(a) – Harmful?#6(a) – Harmful?

Original strand: Original strand: AUG–UUU–UUG–CCU–UAAUG–UUU–UUG–CCU–UAUU–CAU–CGU –CAU–CGU met–phe–leu–pro–met–phe–leu–pro–tyrtyr–his–arg–his–arg

Change to: UAChange to: UACC New protein: New protein:

met–phe–leu–pro–met–phe–leu–pro–tyrtyr–his–arg–his–arg

Silent = not harmfulSilent = not harmful Protein unchangedProtein unchanged

#6(b) – Harmful?#6(b) – Harmful?

Original strand: Original strand: AUG–UUU–UUG–CCU–UAAUG–UUU–UUG–CCU–UAUU–CAU–CGU –CAU–CGU met–phe–leu–pro–met–phe–leu–pro–tyrtyr–his–arg–his–arg

Change to: UAChange to: UAAA New protein:New protein:

met–phe–leu–pro–met–phe–leu–pro–STOPSTOP

Nonsense = harmfulNonsense = harmful Nonfunctioning proteinNonfunctioning protein

#6(c) – Harmful? #6(c) – Harmful?

Original strand: Original strand: AUG–UUU–UUG–CCU–UAU–CAU–CGU AUG–UUU–UUG–CCU–UAU–CAU–CGU met–phe–met–phe–leuleu––propro––tyrtyr––hishis––argarg

New protein: New protein: met–phe–leu–met–phe–leu–alaala––leuleu––leuleu––leu leu

Frameshift mutation = harmful Frameshift mutation = harmful Different amino acids (new protein)Different amino acids (new protein)

insert a C and shift over

#6(d) – Harmful?#6(d) – Harmful?

Original strand: Original strand: AUG–UUU–UUG–CCU–AUG–UUU–UUG–CCU–UUAU–CAU–CGU AU–CAU–CGU met–phe–leu–pro–met–phe–leu–pro–tyrtyr––hishis––argarg

New protein: New protein: met–phe–leu–pro–met–phe–leu–pro–ileile––ileile

Frameshift mutation = harmful Frameshift mutation = harmful Different amino acids (new protein)Different amino acids (new protein)

Delete and shift overand shift over

#7(a) – Single #7(a) – Single SubstitutionSubstitution

Arginine Arginine →→ Leucine Leucine With the following substitutions: With the following substitutions:

CGU CGU →→ CUU CUU CGC CGC →→ CUC CUC CGA CGA →→ CUA CUA CGG CGG →→ CUG CUG

#7(b) – Single #7(b) – Single SubstitutionSubstitution

Cysteine Cysteine →→ Glutamic acid Glutamic acid Cannot be done with one base pair Cannot be done with one base pair

substitutionsubstitution

#7(c) – Single #7(c) – Single SubstitutionSubstitution

Serine Serine →→ Threonine Threonine With the following substitutions: With the following substitutions:

AGU AGU →→ ACU ACU AGC AGC →→ ACC ACC UCU UCU → ACU→ ACU UCC UCC → ACC→ ACC UCA UCA → ACA→ ACA UCG UCG → ACG→ ACG

#7(d) – Single #7(d) – Single SubstitutionSubstitution

Isoleucine Isoleucine →→ Serine Serine With the following substitutions: With the following substitutions:

AUU AUU →→ AGU AGU AUC AUC →→ AGC AGC