Post on 17-Jan-2016
• Chapter 14 Homework is due on Sunday, January 25 at 11:59 pm
• The Chapter 13 and 14 test is on Monday.
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