• Chapter 14 Homework is due on Sunday, January 25 at 11:59 pm

• The Chapter 13 and 14 test is on Monday.

Chapter 14Mutations

You Must Know

• How mutations can change the amino acid sequence of a protein and be able to predict how a mutation can result in changes in gene expression.

Mutagens

Concept 14.5: Mutations of one or a few nucleotides can affect protein structure and function

• Mutations are changes in the genetic material of a cell or virus.

• Point mutations are chemical changes in just one or a few nucleotide pairs of a gene.

• The change of a single nucleotide in a DNA template strand can lead to the production of an abnormal protein.

The molecular basis of sickle-cell disease

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 hemoglobin

ValGlu

• Hemoglobin is made up of four polypeptides. • Hemoglobin alleles are codominant. • What would the hemoglobin of someone who

was heterozygous for sickle cell anemia be like?

• People who are heterozygous for sickle cell anemia don’t have the disease and they are resistant to malaria!

Normal hemoglobin Sickle-cell hemoglobin

ValGlu

Normal polypeptide

Glu

Normal polypeptide

Glu

Sickle-cell polypeptide

Val

Sickle-cell polypeptide

Val

Types of Small-Scale Mutations

• Point mutations within a gene can be divided into two general categories.

–Nucleotide-pair substitutions.

–One or more nucleotide-pair insertions or deletions.

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

Protein

Amino endPhe GlyMet Lys

3 55 35 3

Wild type

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

What would the amino acid sequence be in a silent mutation?

Phe GlyMet Lys

3 55 3

5 3

Stop

A instead of G

Nucleotide-pair substitution: silent

U instead of C

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

• Missense mutations still code for an amino acid, but not the correct amino acid.– Is sickle cell anemia a missense mutation?– Yes.

• Substitution mutations are usually missense mutations.

• Nonsense mutations change an amino acid codon into a stop codon, nearly always leading to a nonfunctional protein.

DNA template strand

mRNA

StopCarboxyl end

Protein

Amino endPhe GlyMet Lys

3 55 35 3

Wild type

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

What would the amino acid sequence be if there were a nonsense mutation at the arrow?

Nucleotide-pair substitution: nonsense

3 55 3

5 3Met

Stop

A instead of T

U instead of A

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

TA T TT A AAT TG G G CG

UA U UU A AAU UG G G CG

Deletion

Insertions and Deletions

• Insertions and deletions are additions or losses of nucleotide pairs in a gene.

• These mutations have a disastrous effect on the resulting protein more often than substitutions do.

• Insertion or deletion of nucleotides may alter the reading frame of the genetic message, producing a frameshift mutation.

DNA template strand

mRNA

StopCarboxyl end

Protein

Amino endPhe GlyMet Lys

3 55 35 3

Wild type

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

What do you call it when there is a frameshift mutation that results in a stop codon at the start of a protein?

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 G

TA T TA A AAT TG G G CG

UA U UA A AAU UG G G CG

A

T

U

DNA template strand

mRNA

StopCarboxyl end

Protein

Amino endPhe GlyMet Lys

3 55 35 3

Wild type

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

What do you call it when there is a frameshift mutation that causes a long string of amino acids to change?

Nucleotide-pair deletion: frameshift causing extensive missense

Leu AlaMet Lys

3 5A

5 3

5 3U

missing

missing

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

Figure 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