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Lec 09 Origins of Variation II.docx
Lec 09 Origins of Variation II.docx

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School
Western University
Department
Biology
Course
Biology 1001A
Professor
Dr.Mike
Semester
Fall

Description
Lecture 09: Origins of Variation II Characteristics of STR loci that make them useful for forensic DNA analysis (DNA fingerprinting) - DNA fingerprinting: unique combinations and variations of the DNA sequence - Short tandem repeat (STR) sequence: loci in noncoding region of genome; short sequence of DNA repeated in series, with each repeat about 3 to 5 bp - Each locus has different repeated sequence and the number of repeats varies among individuals in a population Mechanism of DNA recombination 1. Two molecules of DNA with similar sequence are brought into close proximity - Homologous sequence of bases, allowing DNA molecules to line up and recombine precisely 2. Enzymes nick the DNA backbones, exchange the ends, and reattach them - Covalent bond in each of the four sugar-phosphate backbones broken - Backbones are reattached to another DNA molecule 3. Final result is two recombined DNA molecules - Cutting and pasting four DNA backbones results in one recombination event Stage of meiosis when recombination occurs - Figure 9.10 (Volume 1 page 194) - Figure 9.11 (Volume 1 page 196) - Figure 9.13 (Volume 1 page 199) - Recombination occurs during prophase I - Chromatids of homologous chromosomes undergo recombination by exchanging segments while paired - These chromosomes separate at first meiotic division Incorrect tautomers of bases are not recognized as mismatches - This pairing does not distort the helix (not detectable) - Removed by excision repair instead o Segment of DNA is cut out and replaced with the help of DNA polymerase Mutagenic mechanism of action of base analogues; e.g., 5-bromouracil - Difference between T and U: thymine has a CH on its 3C while uracil has a H on its 5C - If bromine replaces the H in uracil, 5-bromouracil results - Looks very similar to thymine and DNA polymerase has a very hard time distinguishing 5- bromouracil and thymine - Thus 5-bromouracil is a base analogue: gets incorporated into DNA by mistake - Problem: 5-bromouracil is very tautomerically unstable relative to thymine - Powerful mutagen that can happen naturally! Mutagenic mechanism of action of UV radiation - Physical mutagen: UV radiation causes thymine dimers that distort the helix (by reorganizing electrons and bonding in pyrimidine bases) - Ts are hooked; dimer is formed when the bases themselves are hooked together (TT to T^T) - Causes major helix distortion; extremely difficult to replicate through a dimer o DNA polymerase relaxes its pairing rules to get through the dimer (distortion doesn’t properly display hydrogen bonds so polymerase just puts in any base) o Fidelity of replication is relaxed, causing even more damage Mechanisms of repair of UV photodamage - Photolyase (not in mammals) + white light breaks the bonds forming dimers: T^T back to TT
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