18 BIO 326R mutations - BIO 326R Mutations Mutations A...

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BIO 326R Mutations
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Mutations A change in the genetic structure (DNA) of an organism Rarity – in E. coli, ~1/107 to 1/1011 cfu will be mutants Primarily reflects fidelity of DNA replication process (i.e. DNA polymerase usually works pretty well) The mutation rate can be increased by mutagens. In a lab environment, this can be helpful. Common mutagens used include alkylating agents, UV radiation, base analogs. Spontaneous or Induced Spontaneous: error in replication, DNA base chemistry Induced: radiation, chemical and DNA (transposons, viral/phage insertions), other Five or more types Point mutations – single base change Deletions – portion of sequence is lost Insertions – DNA acts as a mutagen Duplications – makes two or more copies of a sequence Transpositions – DNA sequence moves from one place to another
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Spontaneous mutations –  base tautomerization Adoption of the enol tautomer can lead to inappropriate (G:T) base pairing Guanine may also tautomerize to an enol form Cytosine and Adenine can tautomerize to an imino form lead to C:A base pairs N N O O CH 3 H N N O O CH 3 H Keto (normal) form Enol (can base pair with Guanine) Enol tautomerization of Thymine
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Tautomerization Leads to transition mutation (purine for purine or pyrimidine for pyrimidine) Transversion mutations are rarer, due to steric constraints Tautomerization doesn’t cause transversions GAATCC CTTAGG GAA T CC CTT G GG GAATCC CTTAGG T adopts enol form before or during, replication and base pairs with G. May not be repaired since First generation GAATCC CTTAGG GAA C CC CTT G GG GAATCC CTTAGG GAATCC CTTAGG Mutant Second generation
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Mutagens Any agent which causes a mutation is a mutagen Radiation UV: Thymine dimers Gamma, X-rays: formation of radicals and ds breaks Subatomic particles: Alpha radiation, beta radiation, other particles (neutrons etc): radical formation and ds breaks Chemical agents Base analogs – incorporated into DNA during replication Alkylating agents Viruses, phages, transposons DNA insertion into genome
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Base analogs
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This note was uploaded on 04/09/2009 for the course BIO 326R taught by Professor Whiteley during the Spring '08 term at University of Texas at Austin.

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18 BIO 326R mutations - BIO 326R Mutations Mutations A...

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