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Download Gene 1 Gene 2 Gene 3 DNA template strand TRANSLATION mRNA
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DNA molecule Gene 2 Gene 1 Gene 3 DNA template strand TRANSCRIPTION mRNA Codon TRANSLATION Protein Amino acid 1 Third mRNA base (3ʹ′ end of codon) First mRNA base (5ʹ′ end of codon) Second mRNA base 2 Wild-type DNA template strand 3ʹ′ 5ʹ′ 5ʹ′ 3ʹ′ mRNA 5ʹ′ 3ʹ′ Protein Stop Amino end Carboxyl end A instead of G 3ʹ′ 5ʹ′ Extra A 5ʹ′ 3ʹ′ U instead of C 5ʹ′ 5ʹ′ 3ʹ′ 3ʹ′ 5ʹ′ Extra U 3ʹ′ 5ʹ′ 3ʹ′ Stop Stop Silent (no effect on amino acid sequence) Frameshift causing immediate nonsense (1 base-pair insertion) T instead of C missing 3ʹ′ 5ʹ′ 5ʹ′ 3ʹ′ 3ʹ′ 5ʹ′ 5ʹ′ 3ʹ′ A instead of G missing 3ʹ′ 5ʹ′ 5ʹ′ 3ʹ′ Stop Missense Frameshift causing extensive missense (1 base-pair deletion) missing A instead of T 3ʹ′ 5ʹ′ 5ʹ′ 3ʹ′ 3ʹ′ 5ʹ′ 3ʹ′ 5ʹ′ U instead of A 5ʹ′ 5ʹ′ 3ʹ′ missing Stop Stop Nonsense (a) Base-pair substitution 3ʹ′ No frameshift, but one amino acid missing (3 base-pair deletion) (b) Base-pair insertion or deletion 3 Wild-type hemoglobin DNA Mutant hemoglobin DNA C T T C A T 3ʹ′ 5ʹ′ 3ʹ′ 5ʹ′ G T A G A A 3ʹ′ 5ʹ′ mRNA 5ʹ′ 5ʹ′ 3ʹ′ mRNA G A A Normal hemoglobin Glu 3ʹ′ 5ʹ′ G U A 3ʹ′ Sickle-cell hemoglobin Val 4 Normal hemoglobin Primary structure 1 2 3 4 5 6 7 Secondary and tertiary structures β subunit Normal hemoglobin (top view) Val His Leu Thr Pro Val Glu 1 2 3 Normal red blood cells are full of individual hemoglobin moledules, each carrying oxygen. 6 7 β subunit β Sickle-cell hemoglobin α Function α Molecules interact with one another and crystallize into a fiber; capacity to carry oxygen is greatly reduced. 10 µm Red blood cell shape 5 Exposed hydrophobic region β Molecules do not associate with one another; each carries oxygen. 4 α Quaternary structure β Function Secondary and tertiary structures Sickle-cell hemoglobin β α Quaternary structure Primary structure Val His Leu Thr Pro Glu Glu 10 µm Red blood cell shape Fibers of abnormal hemoglobin deform red blood cell into sickle shape. 5
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