Parasites in Your DNA

Parasites in Your DNA

Sarah RosencransZoology Capstone

PresentationMay 5, 2010

http://www.amazon.com/Parasite-Rex-Bizarre-Dangerous-Creatures/dp/074320011X

“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)

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

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.)

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:Barbara_McClintock_at_C.S.H._1947.jpg

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)

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

Transposable Elements• Retrotransposons

–Replicate with RNA intermediate

–Transcribe to DNA with reverse transcriptase

–Reinsert in new location

(Combes, C. 2001. Parasitism)

(Wright, S. and D. Finnegan. 2001. Curr. Bio. 11: 296)

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.)

Transposons in Sexual and Asexual 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

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

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

(Wright, S. and D. Finnegan. 2001. Curr. Bio. 11: 297)

Transmission of TE by Sexual Reproduction

Transposons in Sexual Populations

• 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.

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

(jakst.wordpress.com)(Arkhipova, I. and M. Meselson. 2005. BioEssays 27:76-85)

TE TE

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)

Model for Mating-type Switch in K. lactis

(Barsoum et al. 2010. Genes Dev. 24: 41)

Transposons in Sexual Populations• 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)

Asexuality• Modern asexuals

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. BioEssays 27:76-85) (Schurko et al. 2008. Trends in Ecology and

Evolution 24 (4): 210)

(Wright, S. and D. Finnegan. 2001. Curr. Bio. 11: 297)

Transmission of TE in Asexual Population

Signs of Sex

(Schurko et al. 2008. Trends in Ecology and Evolution. 24(4): 213)

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)

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………

“Ethical stem cells stripped of 'cancer' genes” March 2009

http://io9.com/5162501/insect-parasites-will-cleanse-your-stem-cells-of-cancer

• Researchers reprogrammed cancer causing genes in stem

cells using a transposable element known as piggyBac

http://www.newscientist.com/article/dn16684-ethical-stem-cells-stripped-of-cancer-genes.html

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)

Questions?

http://1.bp.blogspot.com/_DZH2cmCoois/RgQ6JBFexlI/AAAAAAAABmo/o1KTzWltOYw/s400/genome_project_cartoon.png