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Mutations of Many Kinds from Transposons

Mutations of Many Kinds from Transposons. Nov. 3, 2005. common. easy. difficult. ?. rare. Diversity of Mutagenecity. Blocks transcription. Nonfunctional active site. Nonfunctional active site. Partially active. Normal active site. Unremoved interon – stops translation of protein.

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Mutations of Many Kinds from Transposons

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  1. Mutations of Many KindsfromTransposons Nov. 3, 2005

  2. common easy difficult ? rare Diversity of Mutagenecity

  3. Blocks transcription Nonfunctional active site Nonfunctional active site Partially active Normal active site Unremoved interon – stops translation of protein Positions of Mutations

  4. Causes breastcancer Immunoglobulin-Oncogene Combination

  5. Ac/Ds system in Corn • First genetic indication of mutation-causing gene by Marcus Rhoades in 1938 • Analyzed by Barbara McClintock in 1950s • Ds requires presence of Ac • Ds causes chromatid breaks, one always at site of Ds, causingdeletions, insertions, excisions • Dsinactivates adjacent locus, but not always irreversibly • Deletions inAc converts it to Ds • Deletions inDs makes it stable

  6. McClintock’s Observations • Similar pattern found, where allele mutationDs+(normal) changes to Ds (mutant) and corresponded with a chromosome break • Depends on presence of another locus, Ac • Ac mapped to different locations, it “jumped” around • Ds also changed position on the chromosome when Ac is present • A particular cross produced an important kernel with spots of color on clear background, or vice versa, depending on “normal color”

  7. 4563bp TAGGGATGAAA TTTCATCCCTG 5' 3' Transposase Transcription 500bp Transposase mRNA,for a special DNAase Molecular Structure of Ac

  8. Transposase Cuts DNA Splicing ModelTransposon Excision

  9. Alternative Transposase Cuts DNA Splicing ModelTransposon Modification

  10. Ac+becomesDswhen Ac+ present DsbecomesDs2when Ac+ present when Ac+ present Ds2BecomesDs3 Formation of DsfromAc (=Ac+)(in corn)

  11. Phenotypic Expressions Nearby allele may be inactivated to recessive form by being “cut” by transposase. Inactivation of Ds reverts the allele to normal expression. Chromosome breaks before replication, causes bridges and fragments with sister strands.

  12. Hybrid Dysgenesis • Inbred females mated with wild males produce dysgenic offspring --- • High mutation rate • High chromosomal breakage rate • High sterility • High chromosome nondisjunction

  13. Formation of multiple alleles • an example: white-apricot (wa) allele in Drosophila eye color caused by insertion in pigment locus • loci and functions in retroposons may be similar to “normal” loci in eukaryote

  14. Examples of Transposon Activity: • Cause 50% of the spontaneous mutations in Drosophila • Cause red/green color blindness in humans; mutant is because of a 7.2Kbp transposon inserted in the middle of the rhodopsin gene.

  15. Discovery of Bacterial Transposons • 1950’s Shigella in Japanese hospitals found to be resistant to multiple drugs • Resistance genes transferable among different species of bacteria • Transfer was as a “packet”, not one at a time • A common structure was identified …

  16. Loci Common Among species

  17. Functions of transposable elements • Mutagenic by insertion, deletion, epistasis • Generate chromosome rearrangements • Change basic genetic maps among species • Transport genes and exons across species barriers (“lateral transmission” w/o sex) • Deactivate and activate normal genes haphazardly • Modify biochemical and regulatory relationships over time • Increase apparent “relatedness” of species

  18. Modern Genetic Engineering • Artificial chromosome segments with “desired loci” with increased gene activity from another promoter (e.g. viral origin) • Segment inserted at random with a “shotgun” of DNA-linked pellets • Few become inserted into chromosome, at uncontrolled sites, may move over time • These are “synthetic transposons” and have similar properties of “instability”

  19. Ponder these ideas: • Describe the ways that you can identify the differences in structural organization of the chromosomes caused by insertion of transposons affects the function (expression) of the genes when “creating” phenotypes. • Hint: trace the factors that affect the “flow” of information in any form, including “signals,” products formed, roles in molecular processes, development, disease, and integration with environmental factors (living and non-living).

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