Ro_Lecture12

Ro_Lecture12 - 1 Mutations and the code Frameshift...

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Unformatted text preview: 1 Mutations and the code Frameshift mutations A single base-pair deletion or insertion results in a change in the reading frame AUG UUU AG C UUU AGC UUU AGC Met Phe Ser Phe Ser Phe Ser Delete C Insert C 2 Silent Mutations Silent mutations do not alter the amino acid sequence! AUG UUU AGC UUU AGC UUU AGC Met Phe Ser Phe Ser Phe Ser AUG UU C AGC UUU AGC UUU AGC Met Phe Ser Phe Ser Phe Ser Mutations that occur in introns are also silent 3 Missense mutations Missense mutations alters ONE codon so that it encodes a different amino acid UUU UUU UG C UUU UUU Phe Phe Cys Phe Phe 4 Consequences of Missense Mutations Missense mutations alter one of the many amino acids that make a protein Its consequences depend on which amino acid is altered 1 2 3 4 5 Conservative: K to R Nonconservative Surface Vs buried 5 Nonsense mutations Nonsense mutations alter one codon so that it now encodes for a STOP codon UUU UUU UGA UUU UUU Phe Phe STOP Nonsense mutations insert a stop codon which results in premature termination Truncated polypeptide usually results in loss of function for polypeptide 6 Mutations in non-protein coding regions Mutations in the promoter or ribosome binding site are also mutagenic Reduced expression of mRNA might result in reduced levels of proteins Mutations in splicing junctions may also be mutagenic Improperly spliced mRNA will result in the intron being Translated Mutations in tRNA or aminoacyl-tRNA synthase are mutagenic 7 Nonsense suppressor mutations! These are the result of a mutation in the anti-codon loop of a specific tRNA It allows the tRNA to recognize a nonsense codon and base pair with it. DNA Gene encoding tRNA TRP Point mutation occurs in the anticodon loop This allows this tRNA to base pair with a stop codon and ? AUG Trp---UAC--- AUC Trp---UAG--- 8--- UUU UUU UAG UUU UUU -------- Phe Phe STOP 5--- UUU UUU UAG UUU UUU -----3 AUC Trp AAA Met Ala Phe Phe--- Phe Phe Trp Phe Phe ----> A mutant protein that is larger than normal will be synthesized!! 9 Nonsense suppressor--- UUU UUU CAG UUU UUU -------- Phe Phe Gln Phe Phe ------ UUU UUU UAG UUU UUU -------- Phe Phe STOP Nonsense mutation What will happen if an individual carries both a nonsense mutation and a mutation in the anticodon loop of one of the trp-tRNA genes. AUC Trp---UAG--- 5--- UUU UUU UAG UUU UUU -----3 AUC Trp AAA Met Ala Phe Phe 10 Generation of mutations Spontaneous mutations Replication induced mutations of DNA Most spontaneous errors are corrected Usually base substitutions Sometimes small additions and deletions Chemical induced changes Exposure to physical mutagens like radioactivity or chemicals Depurination (removal of adenine or guanine) substitution during replication Deamination (removal of amino group of base) nitrous acid Cytosine--uracil--bp adenine--replication-- Oxidation (oxoG) guanine--oxoguanine--bp adenine--replication -- Base analog incorporation during replication BU-T Intercalating agents X-rays- 11 Recombinant DNA technology When genes are mutated - proteins are mutated-...
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Ro_Lecture12 - 1 Mutations and the code Frameshift...

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