DNAmolecule

Gene 1

Gene 2

Gene 3

DNAtemplatestrand

TRANSCRIPTION

TRANSLATION

mRNA

Protein

Codon

Amino acid

1

Second mRNA base

Fir

st

mR

NA

ba

se

(5

en

d o

f c

od

on

)

Th

ird

mR

NA

ba

se

(3

en

d o

f c

od

on

)

2

Wild-type

3DNA template strand

5

5

53

3

Stop

Carboxyl endAmino end

Protein

mRNA

33

3

55

5

A instead of G

U instead of C

Silent (no effect on amino acid sequence)

Stop

T instead of C

33

3

55

5

A instead of G

Stop

Missense

A instead of T

U instead of A

33

3

5

5

5

Stop

Nonsense No frameshift, but one amino acid missing (3 base-pair deletion)

Frameshift causing extensive missense (1 base-pair deletion)

Frameshift causing immediate nonsense (1 base-pair insertion)

5

5

533

3

Stop

missing

missing

3

3

3

5

55

missing

missing

Stop

5

5533

3

Extra U

Extra A

(a) Base-pair substitution (b) Base-pair insertion or deletion

3

Wild-type hemoglobin DNA

mRNA

Mutant hemoglobin DNA

mRNA

33

3

3

3

3

55

5

55

5

C CT T TTG GA A AA

A A AGG U

Normal hemoglobin Sickle-cell hemoglobin

Glu Val

4

5

Primarystructure

Secondaryand tertiarystructures

Quaternarystructure

Normalhemoglobin(top view)

Primarystructure

Secondaryand tertiarystructures

Quaternarystructure

Function Function

subunit

Molecules donot associatewith oneanother; eachcarries oxygen.

Red bloodcell shape

Normal red bloodcells are full ofindividualhemoglobinmoledules, eachcarrying oxygen.

10 µm

Normal hemoglobin

1 2 3 4 5 6 7

Val His Leu Thr Pro Glu Glu

Red bloodcell shape

subunit

Exposedhydrophobicregion

Sickle-cellhemoglobin

Moleculesinteract withone another andcrystallize intoa fiber; capacityto carry oxygenis greatly reduced.

Fibers of abnormalhemoglobin deformred blood cell intosickle shape.

10 µm

Sickle-cell hemoglobin

GluProThrLeuHisVal Val

1 2 3 4 5 6 7