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Lecture 9

Biology 1001A Lecture 9.pdf

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Biology 1001A
Beth Mac Dougall- Shackleton

Biology 1001A | 2012 LECTURE NOTES Lecture 9: Origin of Variation II –––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– - things move around in your genome, as though your genome was an ecosystem - A-T and G-C is most stable configuration therefore equilibrium favours one tautomer over another Tautomeric Shifts - chemical mutagens - some mutagens are tautomerically unstable base analogues - thymine and uracil differ only in the presence of a methyl group - 5-bromouracil looks a lot like thymine to DNA polymerase - 5-bromouracil is therefore considered a base analogue - this compound can be incorporated into DNA by mistake - this compound is tautomerically unstable, which would cause increased tautomeric shifts and therefore increase the frequency of mutations - this is one mechanism by which chemicals can increase mutation frequency - non-chemical mutagens - tautomeric shifts can occur without chemicals using physical mutagens - UV radiation has enough energy to be absorbed by pyrimidine bases and rearrange parts of the atoms - one such rearrangement is the formation of thymine dimers which are two thymine molecules linked together - thymine dimers distort the helix, which makes it very difficult for polymerases to replicate through a dimer - in some organism, DNA polymerase relaxes its pairing rules to get through the dimer by allowing polymerase to use any nucleotide to fill the gap and continue - this can results in more damage due to the incorrect nucleotides - but without this relaxation of the rules, the cell would die anyway - dimers can be repaired by photolyase or excision - single celled organisms would need to repair, multicellular organisms might let the cell die - the photolyase enzyme uses a photon of blue light to power the repair - plants, archaea, other animals have it, but mammals don’t have photolyase, too bad - mammals can repair the damage using excision repair, which removes the damaged piece via nuclease and replaces it with nucleotides via DNA polymerase, the ends are then resealed using DNA ligase ▯ ▯ Mechanisms of Diversity - variance in ability to repair damage can contribute to differences among organisms of the same species Biology 1001A | 2012 Insertion/Deletion Mechanism - many errors arise during DNA replication - long stretches of DNA can loop and the strand will have too many Ts - this can generate small in/del mutations - triplet repeat mutations are an example of genetic anticipation, where the disease gets worse
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