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the Genetic Code Shown as mRNA 5′ → 3′ 64 codons Redundant One “start” codon: AUG Three “stop” codons: UAG, UAA, UGA (don’t encode amino acids) the Genetic Code For each gene, one DNA strand is transcribed Template strand “read” mRNA complementary to template 5’ CTACGAGGAGGTGAAGCGATGCCCCGTAGCCGATAGTAGC 3’ DNA 3’ GATGCTCCTCCACTTCGCTACGGGGCATCGGCTATCATCG 5’ template strand 5’ CUACGAGGAGGUGAAGCGAUGCCCCGUAGCCGAUAGUAGC 3’ mRNA the Genetic Code Non-template strand looks like RNA (except T’s) also called the sense strand 5’ CTACGAGGAGGTGAAGCGATGCCCCGTAGCCGATAGTAGC 3’ DNA 3’ GATGCTCCTCCACTTCGCTACGGGGCATCGGCTATCATCG 5’ 5’ CUACGAGGAGGUGAAGCGAUGCCCCGUAGCCGAUAGUAGC 3’ non-template strand mRNA the Genetic Code Ribosome starts at 5’ end of mRNA (in eukaryotes) Protein synthesis begins at start codon, ends at stop codon codons 5’ CUACGAGGAGGUGAAGCGAUGCCCCGUAGCCGAUAGUAGC 3’ MetProArgSerArg startthis codon: stop codon stop codon: AUG UAG, UGA or UAA is not “in-frame” so it’s ignored! mRNA protein Mutation Change in nucleotide sequence of DNA Caused by: DNA polymerase mistake Chemical change within cell UV light or other radiation Mutagenic chemical Effects of mutations 5’ DNA ACGATCCTATGCCCCGCAGCCGATAGTCTCATT 3’ 3’ TGCTAGGATACGGGGCGTCGGCTATCAGAGTAA 5’ 5’ RNA ACGAUCCUAUGCCCCGCAGCCGAUAGUCUCAUU 3’ Effects of mutations DNA 5’ ACGATCCTATGCCCCGCAGCCGATAGTCTCATT 3’ 3’ TGCTAGGATACGGGGCGTCGGCTATCAGAGTAA 5’ 5’ RNA ACGAUCCUAUGCCCCGCAGCCGAUAGUCUCAUU MetProArgSerArg 3’ Effects of mutations Missense: single amino-acid change DNA 5’ ACGATCCTATGCCCCGCCGCCGATAGTCTCATT 3’ 3’ TGCTAGGATACGGGGCGGCGGCTATCAGAGTAA 5’ 5’ RNA ACGAUCCUAUGCCCCGCCGCCGAUAGUCUCAUU MetProArg???Arg Could this change have an effect on protein function? Could it affect the whole organism? 3’ Effects of mutations Missense: single amino-acid change DNA 5’ ACGATCCTATGCCCCGCCGCCGATAGTCTCATT 3’ 3’ TGCTAGGATACGGGGCGGCGGCTATCAGAGTAA 5’ 5’ RNA ACGAUCCUAUGCCCCGCCGCCGAUAGUCUCAUU MetProArgArgArg Could this change have an effect on protein function? Could it affect the whole organism? 3’ Effects of mutations Missense: single amino-acid change Wild-type RPE65: ATGTCTATCCAGGTTGAGCATCCTGCTGGTGGTTACAAGAAACTGTTTGAAACTGTGGAGGAACTGTCCT CGCCGCTCACAGCTCATGTAACAGGCAGGATCCCCCTCTGGCTCACCGGCAGTCTCCTTCGATGTGGGCC AGGACTCTTTGAAGTTGGATCTGAGCCATTTTACCACCTGTTTGATGGGCAAGCCCTCCTGCACAAGTT… MetSerIleGlnValGluHisProAlaGlyGlyTyrLysLysLeuPheGluThrValGluGluLeuSerSerPro LeuThrAlaHisValThrGlyArgIleProLeuTrpLeuThrGlySerLeuLeuArgCysGlyProGlyLeuPhe GluValGlySerGluProPheTyrHisLeuPheAspGlyGlnAlaLeuLeuHisLysPheAspPheLysGlu… Mutant RPE65: ATGTCTATCCAGGTTGAGCATCCTGCTGGTGGTTACAAGAAACTGTTTGAAACTGTGGAGGAACTGTCCT CGCCGCTCACAGCTCATGTAACAGGCAGGATCCCCCTCTGGCTCACCAGCAGTCTCCTTCGATGTGGGCC AGGACTCTTTGAAGTTGGATCTGAGCCATTTTACCACCTGTTTGATGGGCAAGCCCTCCTGCACAAGTT… MetSerIleGlnValGluHisProAlaGlyGlyTyrLysLysLeuPheGluThrValGluGluLeuSerSerPro LeuThrAlaHisValThrGlyArgIleProLeuTrpLeuThrSerSerLeuLeuArgCysGlyProGlyLeuPhe GluValGlySerGluProPheTyrHisLeuPheAspGlyGlnAlaLeuLeuHisLysPheAspPheLysGlu… Effects of mutations Missense: single amino-acid change Hemoglobin → sickle-cell anemia: ATGGTGCATCTGACTCCTGAGGAG… MetValHisLeuThrProGluGlu GTG Val Effects of mutations Nonsense: creates stop codon AUGCCCCGCAGCCGAUAG MetProArgSerArg AUGCCCCGCAGCUGAUAG MetProArgSerXXX Effects of mutations Deletion: creates frameshift, changes all following aa’s AUGCCCCGCAGCCGAUAG MetProArgSerArg AUGCCCGCAGCUGAUAG MetProAlaAlaAsp… Effects of mutations Insertion: creates frameshift, changes all following aa’s AUGCCCCGCAGCCGAUAG MetProArgSerArg AUGGCCCCGCAGCUGAUAG MetAlaProGlnProIle… Effects of mutations Silent: DNA changes, but protein doesn’t AUGCCCCGCAGCCGAUAG MetProArgSerArg AUGCCCCGCAGUCGAUAG MetProArgSerArg
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