1. Parasites in Your DNA
Sarah Rosencrans
Zoology Capstone Presentation
May 5, 2010
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. 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. 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. 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. 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. 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. 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. 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. 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
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. 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. Transmission of TE by Sexual Reproduction
(Wright, S. and D. Finnegan. 2001. Curr. Bio. 11:
297)
14. 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.
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. 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)
18. 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)
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. Transmission of TE in Asexual Population
(Wright, S. and D. Finnegan. 2001. Curr. Bio. 11: 297)
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. 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. “Ethical stem cells
stripped of 'cancer'
genes” March 2009
•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
http://io9.com/5162501/insec
t-parasites-will-cleanse-your-
stem-cells-of-cancer
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)
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)