Figure 1: Genetic Mosaicism
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- Roderick Baldwin
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1 I. Gene Mutations a) Germinal Mutations: occur w/in the DNA of stem cells that ultimately form gametes. These are the only mutations that can be transmitted to future generations. b) Somatic Mutations: occur w/in the DNA of body cells over the lifetime of an individual via errors in DNA replication, exposure to environmental mutagens (radiation, chemicals, etc). Are eliminated from the gene pool with the death of the individual. Figure 1: Genetic Mosaicism A mutation during the early embryonic stage of development can be passed to all descendants of the cell in which the mutation originated. Consequently, different phenotypes for the same trait may be observed within a given cell type, a condition called Mosaicism. Figure 1a: Genetic Mosaicism: Heterochromia Early Embryonic Cell Line: Iris Adult Cells: Heterochromatic Iris An example of mosaicism is Heterochromia, a condition in which an individual exhibits two different colors within a body tissue. Affected tissues include the hair, eyes, & skin: a) During embryonic development, a mutation in a cell leads to the expression of a different color within the cell and all its descendants. b) The earlier in development the mutation occurs, the greater the percentage of cells will exhibit the alternate color for a given phenotype. 1
2 II. Base Substitutions/Point Mutations A Base Substitution or Point Mutation is the simplest & most common genetic mutation. These changes involve the replacement, addition, or elimination of a SINGLE nucleotide base within a gene. Base substitutions can be classified as either Transitions or Transversions: Figure 2: Base Substitutions: Transitions Transition Base Substitution: Figure 2a: Base Substitutions: Transversions Transversion Base Substitution: 2
3 Effects of Base Substitutions via Transitions/Transversions Figure 3: Nonsense Mutations Nonsense Mutation: base substitution creating a stop codon w/in mrna where none previously existed. Results in premature polypeptide chain termination during translation; the resulting polypeptide fragment is almost always nonfunctional. Figure 3a: Missense Mutations Missense Mutation: base substitution resulting in the alteration of mrna codons. For example, if an AGU is changed to an AGA, the protein will have an arginine where a serine was meant to go. This might alter the final 3-D shape &/or chemical properties of the resulting polypeptide/protein. 3
4 Figure 3b: Silent Mutations Silent Mutation: base substitution that changes the base sequence without changing the amino acid sequence of the resulting a protein. Usually involves point mutations affecting the 3 base of mrna codons that correspond to the wobble (5 ) base of trna anticodons. For example, if an AGU is changed to an AGC, the protein would still have the appropriate serine at that position. Effects of Nucleotide Deletions & Insertions Deletions or insertions of a number of nucleotide bases within a gene that is not divisible by 3 will result in a reorganization of the mrna reading frame or Frame Shift upon transcription. Figure 4: Frame Shift Mutation via Deletion 4
5 Figure 4a: Frame Shift Mutation via Insertion III. Mutagens Figure 5: Types of Mutagenic Agents Mutagen: 5
6 Figure 5: Chemical Mutagens: Intercalating Agents Intercalating Agents slide between nitrogenous bases of the helix, creating atypical spacing between base pairs. Thus during replication, DNA polymerase may either skip replicating several nucleotides (creating a deletion) or insert extra nucleotides (creating an insertion). Either outcome may lead to a frameshift mutation. Figure 5a: Chemical Mutagens: Base Analogs (5-Bromouracil) Chemicals called Base Analogs are structurally similar to normal nucleotides & can be incorporated into DNA during replication. These base analogs induce mutations because they often have different base-pairing rules than the bases they replace. Other chemical mutagens can modify normal DNA bases, resulting in different base-pairing rules. 6
7 Figure 5b: Physical Mutagens: Ionizing Radiation Strong ionizing radiation like X-rays & gamma rays can cause single & double-stranded breaks in the DNA backbone through the formation of hydroxyl radicals on radiation exposure. Ionizing radiation can also modify bases (deamination of cytosine to uracil, analogous to the action of nitrous acid). Figure 5c: Physical Mutagens: UV Radiation (Thymine Dimers) Pyrimidine Dimers form when adjacent pyrimidines (thymines) bind w/in the SAME polynucleotide strand. Results in a distortion of the DNA helix that may block replication or may result in point mutations or frameshifts. Such mutations frequently occur within skin cells due to their frequent exposure to UV rays from the sun (accumulation of such dimers can contribute to the development of skin cancers). Figure 5d: Dimer Excision Repair 7
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