PCB3063 Exam 4 Chapter 14 Gene Mutation DNA Repair and Transposition 14 1 Mutations occur in regions that code for a protein or within noncoding regions like introns or regulatory sequences May or may not affect phenotype Somatic or germ cells those in germ cells are heritable Spontaneous and Induced Mutations Spontaneous changes in nucleotide sequence that have no known cause assumed to be accidental o Often occur during enzymatic process of DNA replication o Rate of spontaneous mutation is low for all organisms o Rate varied between different organisms o Even within same species spontaneous mutation rate varies between genes Induced Mutations result of natural or artificial agents o 1927 Hermann Muller showed that x rays caused mutations in Drosophila o 1928 Lewis Stadler reported same thing for barley Mutation rate likelihood that a gene will undergo a mutation in a single generation of in forming a single gamete Classification based on location of Mutation Somatic Mutations not occurring in germ cells o Not transmitted to future generations o Not detected in phenotype if recessive Germ line Mutations occurring in gametes Autosomal Mutations within genes on autosomes X linked Mutations on x chromosomes o Somatic mutation have greater effect in males if they re x linked Dominant mutations that occur in adults are often masked by other nonmutant cells in the same tissue that perform the same function Mutations in gametes are of greater significance because they are transmitted as part of the germ line and have potential of being expressed in all cells Inherited autosomal dominant mutations will be expressed phenotypically in first generation Homogametic female may pass x linked recessive mutations in hemizygous male Classification Based on Type of Molecular Change Point mutation or base substitution change of one base pair to another Missense change of one nucleotide of a triplet in a protein coding portion can result in new triplet and new protein Nonsense if triplet is changed to stop codon Silent mutation point mutation alters codon but does not change amino acid Transition if pyrimidine replaces pyrimidine or purine replaces purine Transversion purine replaces pyrimidine or vice versa PCB3063 Exam 4 Frameshift loss or addition of single nucleotide changes how the rest of sequence is read Classification Based on Phenotypic Effects Loss of function reduces or eliminates function of gene product can be dominant or recessive any mutation can cause this effect Null complete loss of function Gain of function gene product with enhanced or new functions most are dominant Visible affect morphological trait alter normal phenotype Nutritional loss of ability to synthesis amino acid or vitamin in bacteria Biochemical sickle cell anemic and hemophilia do not always affect morphological characters effect well being and survival Behavioral difficult to analyze affects behavior patterns Regulatory affects regulation of gene expression inappropriately activate or inactivate expression of a gene Lethal interrupts process essential to survival Tay Sachs and Huntington Conditional expression depends on environment Temperature sensitive at a permissive temperature the mutant gene functions normally but loses function at restrictive temperature Neutral can occur in protein coding region or any part of genome and whose effect on genetic fitness of an organism is negligible 14 2 DNA Replication Errors and Slippage DNA polymerases insert incorrect nucleotides during replication DNA polymerases can usually correct these errors in exonuclease proofreading Replication errors due to mispairing lead to point mutations Tautomers the different forms that bases can take from a single proton shift Insertions or deletions occur when one strand of DNA template loops out polymerase misses looped out nucleotides or when DNA polymerase slips Replication Slippage can occur anywhere common in regions with repeated sequences Tautomeric Shifts Keto enol forms of thymine and guanine and amino imino forms of cytosine and adenine are biologically important Tautomeric shifts can lead to permanent base pair changes and mutations End result is point mutation Depurination and Deamination usually a purine Depurination loss of one of nitrogenous bases in an intact double helical molecule Apurinic State glycosidic bond linking 1 C of deoxyribose and number 9 position of purine ring is broken if not repaired DNA polymerase may insert nucleotide a random at that site PCB3063 Exam 4 Deamination amino group in C or A is converted to a keto group C to U and A to hypoxanthine alteration in base pairing specifies of these two bases in DA replication Oxidative Damage DNA can suffer from byproducts of normal cellular processes Reactive oxygen species generated in normal aerobic respiration Reactive oxidants hydroxyl radicals superoxides and hydrogen peroxide can produce over 100 modifications n DNA 14 3 Mutagens have potential to damage DNA and cause mutations Fungal toxins cosmic rays UV light industrial pollutants X rays Base Analogs biosynthesis will occur Base analogs mutagen that can substitute for purines or pyrimidines during nucleic acid 5 BU 5 bromouracil behaves like thymine halogenated at 5 position of pyrimidine ring if linked to deoxyribose BrdU is formed Presence of bromine atom in place of methyl increases possibility that Tautomeric shift 5 BU also increases UV light sensitivity 2 amino purine 2 AP acts as analog of adenine base pairs with thymine and cytosine Alkylating Intercalating and Adduct Forming Agents Alkylating agent donate alkyl groups to amino or keto groups in nucleotides o Alters base paring leading to mutations o EMS alkylates keto groups in 6 position of guanine and 4 position in thymine Intercalating agents chemicals that have dimensions and shapes that allow them to wedge between base pairs of DNA o Cause base pairs to distorts and DNA unwinds Adduct Forming Agents covalently binds to DNA altering conformation and interfering with replication and repair o Acetaldehyde in cigarette smoke o Heterocyclic amines HCAs cancer causing chemicals created during cooking of meats UV Light Ionizing Radiation Electromagnetic spectrum range of wavelengths Visible waves and longer are benign Shorter wavelengths are more energetic and have potential to do damage Purines a pyrimidines absorb most at 260nm Pyrimidine Dimers chemical species with two identical pyrimidines distort DNA conformation and inhibit
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