William S. Klug Michael R. Cummings Charlotte A. Spencer Concepts of Genetics Eighth Edition Chapter 15 Gene Mutation, DNA Repair, and Transposition Copyright © 2006 Pearson Prentice Hall, Inc. What’s a mutation? Mutations Are Classified in Various Ways Spontaneous, Induced, and Adaptive Mutations Table 15-1 Copyright © 2006 Pearson Prentice Hall, Inc. Classifcation as somatic, germline, autosomal, X-linked, recessive, dominant “haploinsufficiency” Classification Based on Phenotypic Effects Loss-of-function Gain-of-function Morphological Nutritional Behavioral Lethal Conditional The Spontaneous Mutation Rate Varies Greatly among Organisms Deleterious Mutations in Humans Table 15-2 Copyright © 2006 Pearson Prentice Hall, Inc. Molecular nature of mutations base substitution transition transversion Figure 15-1 Copyright © 2006 Pearson Prentice Hall, Inc. Spontaneous (and induced) Mutations Arise from Replication Errors and Base Modifications DNA Replication Errors Replication Slippage Tautomeric Shifts Figure 15-2 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 15-2a Copyright © 2006 Pearson Prentice Hall, Inc. Figure 15-2b Copyright © 2006 Pearson Prentice Hall, Inc. Figure 15-3 Copyright © 2006 Pearson Prentice Hall, Inc. Damage versus mutation Depurination and Deamination Figure 15-4 Copyright © 2006 Pearson Prentice Hall, Inc. Oxidative Damage Induced Mutations Arise from DNA Damage Caused by Chemicals and Radiation Base Analogs Figure 15-5 Copyright © 2006 Pearson Prentice Hall, Inc. Alkylating Agents Figure 15-6 Copyright © 2006 Pearson Prentice Hall, Inc. crosslinks Table 15-3 Copyright © 2006 Pearson Prentice Hall, Inc. Acridine Dyes and Frameshift Mutations Intercalating agents Figure 15-7 Copyright © 2006 Pearson Prentice Hall, Inc. Radiation can induce mutations Figure 15-8 Copyright © 2006 Pearson Prentice Hall, Inc. Ultraviolet Light and Thymine Dimers Figure 15-9 Copyright © 2006 Pearson Prentice Hall, Inc. Ionizing Radiation Figure 15-10 Copyright © 2006 Pearson Prentice Hall, Inc. Trinucleotide Repeats in Fragile X Syndrome, Myotonic Dystrophy, and Huntington Disease “Dynamic mutations” Genetic anticipation Table 15-4 Copyright © 2006 Pearson Prentice Hall, Inc. Cleary and Pearson (2005) Trends in Genetics 21:272-280 Genetic Techniques, Cell Cultures, and Pedigree Analysis Are All Used to Detect Mutations Detection in Bacteria and Fungi Detection in Plants Detection in Humans Figure 15-11 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 15-12 Copyright © 2006 Pearson Prentice Hall, Inc. The Ames Test Is Used to Assess the Mutagenicity of Compounds Figure 15-13 Copyright © 2006 Pearson Prentice Hall, Inc. Organisms Use DNA Repair Systems to Counteract Mutations Proofreading and Mismatch Repair Postreplication Repair SOS Response This is not repair! It is an example of damage tolerance. Figure 15-14 Copyright © 2006 Pearson Prentice Hall, Inc. SOS Response Pol V is induced and is error-prone. http://www.science.siu.edu/microbiology/micr460/460%20Pages/SOS.html Photoreactivation Repair: Reversal of UV Damage in Prokaryotes Figure 15-15 Copyright © 2006 Pearson Prentice Hall, Inc. Base and Nucleotide Excision Repair Note: the sugar-phosphate residue must be removed. This is believed to be accomplished by DNA pol β. Figure 15-16 Copyright © 2006 Pearson Prentice Hall, Inc. β Figure 15-17 Copyright © 2006 Pearson Prentice Hall, Inc. Xeroderma Pigmentosum and Nucleotide Excision Repair in Humans Also—defects in pol (eta) Figure 15-18 Copyright © 2006 Pearson Prentice Hall, Inc. Double-Strand Break Repair in Eukaryotes Homologous recombinational repair (HR, HDR) (particularly active in S/G2) Nonhomologous endjoining (NHEJ) (particularly active in G1) Transposable Elements Move within the Genome and May Disrupt Genetic Function Insertion Sequences Figure 15-19 Copyright © 2006 Pearson Prentice Hall, Inc. Bacterial Transposons Often carry genes encoding antibiotic resistance. Figure 15-20 Copyright © 2006 Pearson Prentice Hall, Inc. The Ac–Ds System in Maize Figure 15-22 Copyright © 2006 Pearson Prentice Hall, Inc. Figure 15-22a Copyright © 2006 Pearson Prentice Hall, Inc. Figure 15-22b Copyright © 2006 Pearson Prentice Hall, Inc. Figure 15-22c Copyright © 2006 Pearson Prentice Hall, Inc. Figure 15-23 Copyright © 2006 Pearson Prentice Hall, Inc. Breakage-fusion-bridge cycle www.biologie.uni-hamburg.de/b-online/ge21/18.jpg Mobile Genetic Elements and Wrinkled Peas: Mendel Revisited Copia Elements in Drosophila Figure 15-24 Copyright © 2006 Pearson Prentice Hall, Inc. P Element Transposons in Drosophila (transpose in germ line) Transposable Elements in Humans LINES and SINES 50% of genome is comprised of transposons