06_20_cancer_age.jpg Gene Mutation: Origins and Repair Processes GAATTC GTATTC A a Skin cancers from Xeroderma pigmentosum, a recessive hereditary disease caused by a deficiency in a DNA repair enzyme Mutations DNA Gene Mutational event Mutated gene TranscriptionTranslation Normal protein gene product Normal Phenotype Abnormal protein gene product partially functional partially functional nonfunctional nonfunctional no gene product no gene product Altered PhenotypeGene: nucleotide sequence on a chromosome that encodes a specific protein DNA Mutations: An Overview Heritable changes in base sequences that modify the information content of DNA Forward mutation: a mutation that changes the wildtype allele of a gene to a different allele. The resultant allele can be either dominant or recessive to the original wildtype Mutations A+A+A+A+a a+a+a+a+ A Forward Recessive Forward Dominant Reverse mutation or reversion : a mutation that causes a mutant allele to revert back to wildtype. A+A+A+A+a a+a+a+a+ A Remember: Remember: wild alleles designated with a + La mayora de las mutaciones ocurre durante la replicacin del DNA o durante su reparacin Mistakes during DNA replication can also alter genetic information Replication errors are extremely rare, generally occurring once per 10 9 base pairs The rate of replication errors is kept low due to correction or proofreading activity, which reduces the error rate to one in 10 6 bases copied by DNA polymerase (in vitro) Both DNA polymerase I and II have proofreading ability. It is a 3 to 5 nuclease activity Classes of DNA mutations Substitution: base at certain position is substituted by one of other 3 bases by one of other 3 bases Transition* Transition* purine ( A/G ) for purine or pyrimidine ( C/T ) for pyrimidine Transversion G C Transversion purine ( A/G ) to pyrimidine (C/T) or visa versa Deletion Mutation: block of ONE or more nucleotide pairs is lost from a DNA molecule Insertional Mutation: block of ONE or more nucleotide pairs is added to a DNA molecule Inversion Mutations: 180 rotation of segment of DNA moleculeTranslocations: nonhomologous Parts of nonhomologous chromosomes change place Overview Hereditable change in DNA resulting from change in nucleotide sequence Mutation changes one allelic form to another and is the ultimate source of genetic variation. Mutational variation underlies the study of genetics. Mutations are produced by mutagens or occur spontaneously. Each base pair has a certain probability of undergoing change Point mutations include single base-pair substitutions, additions or deletions. Specialized forms of mutation include expansion of trinucleotide repeats and insertion of transposable elements. Many types of mutation can be repaired. Mutation Hereditable change in DNA resulting from change in nucleotide sequence Multiple causes DNA replication/repair errors Mutagens; spontaneous DNA damage Insertion of transposons Several categories of mutation Point mutations Swap one base for another; insert a base; delete a base Alter the number of copies of a short repeat Large insertions into a gene Point Mutations Single or few base pair changes Provide background rate of mutation critically important to evolution More likely to lead to loss of function than gain of function Origin of point mutation Induced, by geneticist for example action of mutagen; environmental agent that alters nucleotide sequence process of inducing mutations by mutagens called mutagenesis Spontaneous arise in absence of known mutagen may be caused by errors in DNA replication Types of point mutation Base substitution transition A G (purine purine) (AT GC) C T (pyrimidine pyrimidine) (CG TA) transversion purine pyrimidine (e.g., A C) (AT CG) Addition or deletion of nucleotide pairs (base-pair addition or deletion) also called indel mutations Molecular Consequences Terminacin Prematura por mutaciones sin sentido (non sense) Mutacines supresoras intragnicas Figure 27.27: How an intergenic suppression mutation can overcome a nonsense mutation. Efecto de mutaciones supresoras intergnicas Mutacin supresora Ambar Mutacin supresora Opalo