Mutations

Mutations• changes in the

genetic material • Point mutations

changes in one or a few nucleotide pairs of a gene

• can lead to the production of an abnormal protein

Figure 14.25

AG G

Wild-type hemoglobin

mRNA

53

mRNA

Wild-type hemoglobin DNA

535

3TC C

TG GAC C 5

3

AG G5 53 UG G 3

Normal hemoglobin

Sickle-cell hemoglobin

Mutant hemoglobin DNA

Sickle-cell hemoglobinValGlu

Sickle Cell Anemia

Substitutions

• A nucleotide-pair substitution replaces one nucleotide and its partner with another pair of nucleotides

• Silent mutations have no effect on the amino acid produced by a codon because of redundancy in the genetic code

Figure 14.26a

DNA template strand

mRNA

StopCarboxyl end

ProteinAmino end

Phe GlyMet Lys

3 55 35 3

Wild type

Phe GlyMet Lys

3 55 3

5 3

Stop

A instead of GNucleotide-pair substitution: silent

U instead of C

T A T T A A A A T TC C C C GTA T TA A AAT TG G G CG

UA U UA A AAU UG G G CG

T A T T A A A A T TC C C C ATA T TA A AAT TG G G TG

UA U UA A AAU UG G G UG

Gene mutation: Substitution

Substitutions• Missense mutations still code for an amino acid, but not the

correct amino acid• Substitution mutations are usually missense mutationsFigure 14.26b

DNA template strand

mRNA

StopCarboxyl end

ProteinAmino end

Phe GlyMet Lys

3 55 35 3

Wild type

Phe SerMet Lys

3 55 3

5 3Stop

T instead of C

A instead of G

Nucleotide-pair substitution: missense

T A T T A A A A T TC C C C GTA T TA A AAT TG G G CG

UA U UA A AAU UG G G CG

T A T T A A A A T TC C T C GTA T TA A AAT TG A G CG

UA U UA A AAU UG A G CG

Substitutions

• Nonsense mutations change an amino acid codon into a stop codon, usu. a nonfunctional protein

Figure 14.26c

DNA template strand

mRNA

StopCarboxyl end

ProteinAmino end

Phe GlyMet Lys

3 55 35 3

Wild type

Nucleotide-pair substitution: nonsense

3 55 3

5 3Met Stop

A instead of T

U instead of A

T A T T A A A A T TC C C C GTA T TA A AAT TG G G CG

UA U UA A AAU UG G G CG

T A A T A A A A T TC C C C GTA T TT A AAT TG G G CG

UA U UU A AAU UG G G CG

Insertions and Deletions• Insertions and deletions are additions or losses of nucleotide pairs in a gene• disastrous effects on the resulting protein • may alter the reading frame, producing a frameshift mutation

Figure 14.26d

DNA template strand

mRNA

StopCarboxyl end

ProteinAmino end

Phe GlyMet Lys

3 55 35 3

Wild type

Nucleotide-pair insertion: frameshift causing immediate nonsense

Met

3 55 3

5 3

Stop

Extra A

Extra U

T A T T A A A A T TC C C C GTA T TA A AAT TG G G CG

UA U UA A AAU UG G G CG

T A T T A A A A T TC C C C GTA T TA A AAT TG G G CG

UA U UA A AAU UG G G CG

AT

U

Gene Mutation: Deletion or Insertion?

Gene Mutation:

Insertion

Deletion

w/FrameshiftFigure 14.26e

DNA template strand

mRNA

StopCarboxyl end

Protein

Amino endPhe GlyMet Lys

3 55 35 3

Wild type

Nucleotide-pair deletion: frameshift causing extensive missense

Leu AlaMet Lys

3 5A

5 3

5 3U

missing

missing

T A T T A A A A T TC C C C G

TA T TA A AAT TG G G CG

UA U UA A AAU UG G G CG

T A T T A AG

A T TC C C C G

TA T TA A AATG G CG

UA U UA A AAG UG G CG

w/no frameshiftFigure 14.26f

DNA template strand

mRNA

StopCarboxyl end

Protein

Amino endPhe GlyMet Lys

3 55 35 3

Wild type

3 nucleotide-pair deletion: no frameshift, but one amino acidmissing

GlyMet Phe

3 5T T C

5 3

5 3A GA

Stop

missing

missing

T A T T A A A A T TC C C C G

TA T TA A AAT TG G G CG

UA U UA A AAU UG G G CG

T A A A C C GC A A T T

TA G GT T CT T A AG

UA U U UG G G C U A A

Mutagens

• Spontaneous mutations can occur during DNA replication, recombination, or repair

• Mutagens are physical or chemical agents that can cause mutations

• Most carcinogens are mutagenic and visa versa