Parasites in Your DNA         Sarah Rosencrans   Zoology Capstone Presentation            May 5, 2010
“For Dawkins, parasitism is not what some                  particular flea or thorny-headed worm does.                 Par...
Objectives• Definition of parasitism• Mobile Genetic Elements   – Short History   – Transposons• Selfish DNA• Transposons ...
Defining Parasitism• What is a parasite?  “Parasitism is any arrangement in which one set of DNA is    replicated with the...
History of Mobile Genetic Elements • Barbara McClintock   – 1948: discovered     jumping genes in     corn   – Genes appea...
Mobile Genetic Elements• 3 types that may be parasitic   – Repeated sequences   – Pseudogenes   – Transposable Elements• S...
Transposable Elements• Transposons  –Excise and    reinsert at new    location  –Replicate and    reinsert at new    locat...
Transposable Elements• Retrotransposons  – Replicate with    RNA intermediate  – Transcribe to    DNA with reverse    tran...
Selfish DNA• A piece of DNA that “spreads by forming additional  copies of itself within the genome” and has no direct  be...
Transposons in Sexual andAsexual organisms• Self-replication not enough, must have  host replication• If TE is not benefic...
Transposons in Sexual Populations• Ability to colonize new  genomes during zygote  formation (Hickey, D.A. 1982.  Genetics...
Transposons in Sexual Populations        • If TE reduces fitness, how do they spread?           – Initial rate of spread m...
Transmission of TE by Sexual Reproduction       (Wright, S. and D. Finnegan. 2001. Curr. Bio. 11:       297)
Transposons in SexualPopulations• If TE depends on sex to spread, do they  cause sex? Or is sex a defense against  TE?• Al...
Transposable Elements and Sex• Hickey’s hypothesis requires:   – Transposable element that favors sex   – Evidence of tran...
α3, TE that favors sex• Recent study: not all TE are “junk DNA”• TE favors sexual reproduction in yeast   – Kluyveromyces ...
Model for Mating-type Switch in K. lactis                    (Barsoum et al. 2010. Genes Dev. 24: 41)
Transposons in SexualPopulations• Transposable elements occur in higher  levels in sexual organisms than asexual   – Human...
• Modern asexuals                             Asexuality  evolved from sexual  organisms• Have few TE   – TE are deleterio...
Transmission of TE in Asexual Population        (Wright, S. and D. Finnegan. 2001. Curr. Bio. 11: 297)
Signs of Sex(Schurko et al. 2008. Trendsin Ecology and Evolution.24(4): 213)
Evolution of sex and transposons• Cytosine Methlyation   – Sexual organisms’ defense     against TE• Sexual reproduction  ...
Parasitic DNA: Some Conclusions• TE makes sexual reproduction  competitive with asexual  reproduction• TE gives insight in...
“Ethical stem cells                                  stripped of cancer                                  genes” March 2009...
In Conclusion…• “Although the beneficent genome  model currently prevails, it should be  recognized that the structure of ...
Questions?http://1.bp.blogspot.com/_DZH2cmCoois/RgQ6JBFexlI/AAAAAAAABmo/o1KTzWltOYw/s400/genome_project_cartoon.png
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  • Transposons have terminal inverted repeats and encode a single protein, transposase, for transpositions. (Wright, S. and D. Finnegan. 2001. Curr. Bio. 11: R296)
  • Retrotransposons. LTR retrotransposons have long direct repeats, LTRs, at their termini and coding sequences similar to the gag and pol genes of a retrovirus; some, like the gypsy element of Drosophila, have an env like gene as well. Non-LTR retrotransposons have no terminal repeats and usually have two coding sequences. The first, NAB, codes for a nucleic acid binding protein and the second, RT, a protein with reverse transcriptase activity. (Wright, S. and D. Finnegan. 2001. Curr. Bio. 11: 296)
  • Natural selection within the context of the genome as opposed to the whole organismTrait being passed on without any perceived benefitCause disease and mutation, but host survives—comparable to a not too harmful parasite within its host (Orgel and Crick 1980)Transposon is selfish DNA
  • Figure 8. Model for mating-type switch in K. lactis. (A) In MATacells, binding of Mts1 to two sites close to the L repeat is importantto induce switching. The a3 transposase-like proteinpresumably acts at sites flanking the MATa3 gene, resulting inexcision of an a3 gene circle. The circles are lost in subsequentcell cycles, as they lack an origin of replication. The resultingDNA lesions are channeled into a gene conversion pathway, inwhich the repetitive L and R sequences, present also at the HMRalocus, act as blocks of homology to resolve the recombinationintermediates. (B) In MATa cells, binding of Mts1 to several sitesin the MATa1– MATa2 intergenic region induces switching. Anunknown protein generates a hairpin-capped DSB. The hairpin isopened in an Mre11-dependent manner, and the DSB inducesa gene conversion using the HMLa locus as donor sequence.
  • Transposons may be why sexuality has an advantage over asexuality
  • Figure 1. Transposon dispersal in out-crossing sexual hosts. Transposons are black; when an infected genome (red) is brought together with an uninfected genome (orange), replicative transposition causes an increase in the number of infected genomes. Under conditions optimal for the transposon and in a host undergoing preplacement reproduction the number of infected genomes will double in each generation; a transposon that always infects a previously uninfected genome in the zygote or germ line will therefore go to fixtation if it reduces fitness by anything less than 2x. In other words, an efficient transposon will spread through a pouplation if it kills less than half of the offspring in each generation. In an asexual host population that isogenic apart from the transposon, a transposon that decreases fitness by any increment will go to extinction (Bestor 2003)
  • Parasites in Your DNA

    1. 1. Parasites in Your DNA Sarah Rosencrans Zoology Capstone Presentation May 5, 2010
    2. 2. “For Dawkins, parasitism is not what some particular flea or thorny-headed worm does. Parasitism is any arrangement in which one set of DNA is replicated with the help of – and at the expense of – another set of DNA.” (Zimmer, C. 2000. Parasite Rex, 126)http://www.amazon.com/Parasite-Rex-Bizarre-Dangerous-Creatures/dp/074320011X
    3. 3. Objectives• Definition of parasitism• Mobile Genetic Elements – Short History – Transposons• Selfish DNA• Transposons in sexual and asexual organisms – Transposable element that favors sex – Asexuality and transposable elements – Transposons, sexuality, and evolution• Conclusions and research
    4. 4. Defining Parasitism• What is a parasite? “Parasitism is any arrangement in which one set of DNA is replicated with the help of – and at the expense of– another set of DNA.” Richard Dawkins in Parasite Rex – Earliest parasites were bits of DNA that replicated themselves faster than other DNA – Evolution driven by parasitic DNA (Zimmer, C. 2000. Parasite Rex.)
    5. 5. History of Mobile Genetic Elements • Barbara McClintock – 1948: discovered jumping genes in corn – Genes appeared to relocate to different areas of the genome http://commons.wikimedia.org/wiki/File:Barbar a_McClintock_at_C.S.H._1947.jpg
    6. 6. Mobile Genetic Elements• 3 types that may be parasitic – Repeated sequences – Pseudogenes – Transposable Elements• Strong evidence for transposable elements (TE) being parasitic – Self-replicating – Spread through host DNA (Combes, C. 2001. Parasitism)
    7. 7. Transposable Elements• Transposons –Excise and reinsert at new location –Replicate and reinsert at new location (Combes, C. 2001. Parasitism) http://www.anselm.edu/homepage/jpitocch/ genbio/transposons.JPG
    8. 8. Transposable Elements• Retrotransposons – Replicate with RNA intermediate – Transcribe to DNA with reverse transcriptase – Reinsert in new location (Wright, S. and D. Finnegan. 2001. Curr. Bio. 11: 296) (Combes, C. 2001. Parasitism)
    9. 9. Selfish DNA• A piece of DNA that “spreads by forming additional copies of itself within the genome” and has no direct benefit to the host.• Large sections of DNA in organisms have non-specific functions – Ought to disappear with natural selection• Persist because self-replicating – “after a sufficient time, only the most efficient replicators survive” (Orgel, L.E. and F.H.C. Crick. 1980. Nature. 284: 604.)
    10. 10. Transposons in Sexual andAsexual organisms• Self-replication not enough, must have host replication• If TE is not beneficial, how does it evolve? – Host sexual reproduction • Selective advantage • Genetic recombination – Host asexual reproduction • No selective advantage • No genetic recombination- thus mobile elements overwhelm host DNA
    11. 11. Transposons in Sexual Populations• Ability to colonize new genomes during zygote formation (Hickey, D.A. 1982. Genetics. 101) – Transposition occurs between homologous chromosomes – Even heterozygote for TE will have almost all gametes containing element • Mendelian heterozygote: only half of the gametes have a gene Schurko et al. 2008. Trends in Ecology and Evolution. 24(4): 211
    12. 12. Transposons in Sexual Populations • If TE reduces fitness, how do they spread? – Initial rate of spread must be about twice the reproductive rate of its host genome (Hickey, D.A. 1982. Genetics. 101:519-531) – Can spread within a sexual population as long as fitness is reduced by no more than half (Bestor, T.H. 1999. Genetica. 107:289-295) – Spread depends on bi-parental genome reproduction • Does not require sex
    13. 13. Transmission of TE by Sexual Reproduction (Wright, S. and D. Finnegan. 2001. Curr. Bio. 11: 297)
    14. 14. Transposons in SexualPopulations• If TE depends on sex to spread, do they cause sex? Or is sex a defense against TE?• Alternative explanation for sex – “molecular symbionts” that promote sex would account for the evolution of sex (Hickey, D.A. 1993. J. Hered. 84:410-414) – Short term explanation • Select for sex for sake of own propagation • Long term advantages of genetic recombination a consequence not a reason• Thus, sex is an evolutionary response to parasitic DNA.
    15. 15. Transposable Elements and Sex• Hickey’s hypothesis requires: – Transposable element that favors sex – Evidence of transposable elements in sexual organisms – No transposable elements in asexual organisms TE TE (jakst.wordpress.com) (Arkhipova, I. and M. Meselson. 2005. BioEssays 27:76-85)
    16. 16. α3, TE that favors sex• Recent study: not all TE are “junk DNA”• TE favors sexual reproduction in yeast – Kluyveromyces lactis • Normally produces haploid gametes • Addition of transposase-like protein α3 causes mating-type switch • Yeast now produces diploid gametes • Progeny will produce diploid gametes – Evidence that TE may have a role in host sexuality – More research needed to support theory (Barsoum et al. 2010. Genes Dev. 24: 33-44)
    17. 17. Model for Mating-type Switch in K. lactis (Barsoum et al. 2010. Genes Dev. 24: 41)
    18. 18. Transposons in SexualPopulations• Transposable elements occur in higher levels in sexual organisms than asexual – Human DNA is 50% transposons – Nematode is 5% transposons (Wright, S. and D. Finnegan. 2001. Curr. Bio. 11: R296)• High number of transposons=sexual organism – TE would accumulate in asexuals and deleterious effects would drive them to extinction (Schurko et al. 2008. Trends in Ecology and Evolution 24 (4): 210)
    19. 19. • Modern asexuals Asexuality evolved from sexual organisms• Have few TE – TE are deleterious if they accumulate – Asexuals go extinct if “transposition continues to occur when meiosis is abandoned” (Arkhipova, I. and M. Meselson. 2005. (Schurko et al. 2008. Trends in Ecology and BioEssays 27:76-85) Evolution 24 (4): 210)
    20. 20. Transmission of TE in Asexual Population (Wright, S. and D. Finnegan. 2001. Curr. Bio. 11: 297)
    21. 21. Signs of Sex(Schurko et al. 2008. Trendsin Ecology and Evolution.24(4): 213)
    22. 22. Evolution of sex and transposons• Cytosine Methlyation – Sexual organisms’ defense against TE• Sexual reproduction minimizes deleterious effects of TE – Sex may be dependent on TE and TE may be dependent on sex (Arkhipova, I.R. 2005. Cytogenetic and Genome Research 110: 372-382.) (Bestor, T.H. 2003. Trends in Genetics 19(4): 186)
    23. 23. Parasitic DNA: Some Conclusions• TE makes sexual reproduction competitive with asexual reproduction• TE gives insight into evolution – In general – Evolution of sex• Mobile genetics elements potential in research in evolution and medicine And in the news………
    24. 24. “Ethical stem cells stripped of cancer genes” March 2009 •Researchers reprogrammed cancer causing genes in stemcells using a transposable element known as piggyBachttp://www.newscientist.com/article /dn16684-ethical-stem-cells- stripped-of-cancer-genes.html http://io9.com/5162501/insec t-parasites-will-cleanse-your- stem-cells-of-cancer
    25. 25. In Conclusion…• “Although the beneficent genome model currently prevails, it should be recognized that the structure of the genome has been determined in large part not by sound engineering practices or by evolutionary forces that are guiding the genome towards perfection, but by unending conflict between transposons and sexual genomes.” (Bestor, T.H. 2003. Trends in Gen. 19: 189)
    26. 26. Questions?http://1.bp.blogspot.com/_DZH2cmCoois/RgQ6JBFexlI/AAAAAAAABmo/o1KTzWltOYw/s400/genome_project_cartoon.png

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