Jumping genes and epigenetics: Towards new species

Abstract

Transposable elements (TEs) are responsible for rapid genome remodelling by the creation of new regulatory gene networks and chromosome restructuring. TEs are often regulated by the host through epigenetic systems, but environmental changes can lead to physiological and, therefore, epigenetic stress, which disrupt the tight control of TEs. The resulting TE mobilization drives genome restructuring that may sometimes provide the host with an innovative genetic escape route. We suggest that macroevolution and speciation might therefore originate when the host relaxes its epigenetic control of TEs. To understand the impact of TEs and their importance in host genome evolution, it is essential to study TE epigenetic variation in natural populations. We propose to focus on recent data that demonstrate the correlation between changes in the epigenetic control of TEs in species/populations and genome evolution.

Full text

Review
Jumping genes and epigenetics: Towards new species
Rita Rebollo
a
, Béatrice Horard
b
, Benjamin Hubert
a
, Cristina Vieira
a,
⁎
a
CNRS, UMR558, Laboratoire de Biométrie et Biologie Evolutive, Université Lyon 1, Villeurbanne, France
b
Laboratoire de Biologie Moléculaire de la Cellule-UMR 5239 CNRS;ENS LYON; Université LYON 1; HCL. 165, Chemin du Grand Revoyet, 69495 Pierre Bénite or 46, allée d'Italie,
69364 Lyon cedex 07, France
abstractarticle info
Article history:
Received 24 November 2009
Received in revised form 6 January 2010
Accepted 19 January 2010
Available online 25 January 2010
Received by Prescott Deininger
Keywords:
Transposable elements
Evolution
Rapid speciation
Natural populations
Epigenetic control
Transposable elements (TEs) are responsible for rapid genome remodelling by the creation of new regulatory
gene networks and chromosome restructuring. TEs are often regulated by the host through epigenetic
systems, but environmental changes can lead to physiological and, therefore, epigenetic stress, which disrupt
the tight control of TEs. The resulting TE mobilization drives genome restructuring that may sometimes
provide the host with an innovative genetic escape route. We suggest that macroevolution and speciation
might therefore originate when the host relaxes its epigenetic control of TEs. To understand the impact of
TEs and their importance in host genome evolution, it is essential to study TE epigenetic variation in natural
populations. We propose to focus on recent data that demonstrate the correlation between changes in the
epigenetic control of TEs in species/populations and genome evolution.
© 2010 Elsevier B.V. All rights reserved.
1. Introduction
Speciation can be a slow process in which genetic differences
between individuals become fixed, either as a result of changes in their
fitness, ecological specialization, or simply the induction of genetic
incompatibility, followed in both cases by micro-population isolation.
Speciation is also thought to happen quickly in the context of “non-
genic”speciation, i.e., when important karyotypic differences between
individuals of the same species lead to sexual isolation. Our explo-
ration of the dynamics of transposable elements (TEs) in natural pop-
ulations led us to ask how TE mobilization is involved in speciation
(Vieira et al., 1999; Rebollo et al., 2008; Fablet et al., 2009). In this
short-review we argue that TEs are able to induce speciation through
chromosomal rearrangements since, 1) chromosomal rearrangements
are able to induce speciation (Noor et al., 2001; Baird et al., 2009; Greig,
2009), 2) bursts of TE transposition can cause chromosomal rearrange-
ments (Geurts et al., 2006; Weil, 2009; Zhang et al., 2009), and 3)
bursts of TE transposition may be driven by the selective release of
active elements as the result of an epigenetic response to the envi-
ronment (Lisch, 2009). We also discuss the importance of TE-induced
speciation compared to that of other speciation mechanisms.
2. Transposable elements and the genome: a partnership on
the move
Genome-sequencing programs have provided new clues explain-
ing the lack of correlation between phenotypic complexity and ge-
nome size—which is known as the “C value”paradox—by revealing
that most of the differences in genome size between species reside
in the non-coding parts (reviewed in Biemont and Vieira, 2006). For
instance, the human genome is composed of ∼98% of non-coding DNA
(International Human Genome Sequencing Consortium, 2004),
whereas the fruit fly, Drosophila melanogaster, has a very compact
genome with far fewer sequences of this type (Dowsett and Young,
1982; Hoskins et al., 2002; Kaminker et al., 2002; Clark et al., 2007).
This variable part of the genome consists mostly of repetitive
sequences, such as satellite DNAs and TEs. We will focus mainly on the
latter in this short review (see Fig. 1 for a classification of eukaryotic
TEs). The evolutionary importance of TEs is no longer open to question.
In general, all families of DNA repeats could potentially have an impact
on genome organization, either by generating genome instability,
since multicopy elements are known to be powerful recombinogenic
substrates (Hedges and Deininger, 2007), or as being components of
essential chromosomal domains, such as centromeres and telomeres
in many species (Wong and Choo, 2004; Lamb et al., 2007). It is clear
that TE replication might induce genetic mutations via transposition,
as reported for some maize lineages, where Ac/Ds alternative trans-
position (from the ends of two different elements) is directly re-
sponsible for major chromosomal rearrangements (translocations,
duplications, inversions…)(Zhang et al., 2009). The immediate effects
Gene 454 (2010) 1–7
Abbreviation: TE, Transposable element.
⁎Corresponding author. Tel.: +33 4 72 43 29 18; fax: +33 4 72 43 13 88.
E-mail address: vieira@biomserv.univ-lyon1.fr (C. Vieira).
0378-1119/$ –see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.gene.2010.01.003
Contents lists available at ScienceDirect
Gene
journal homepage: www.elsevier.com/locate/gene

of transposition can be detrimental, as illustrated by several human
diseases (reviewed in Callinan and Batzer, 2006). Despite these dam-
aging effects, TEs have been maintained in almost all genomes either
as full-length or truncated copies. Full-length copies have kept their
ability to mutate the genome as a result of transposition, while the
truncated copies have often lost their capacity to transpose. However,
the truncated versions might also be recruited by the genome. Indeed,
recent reports have proposed a scenario of co-evolution of TEs and
hosts, in which TEs (often as truncated copies) are involved in complex
genomic processes such as post transcriptional gene regulation, gene
protein translation enhancement, etc. (Muotri et al., 2007; Sinzelle
et al., 2009). Truncated copies may also act as recombinogenic sub-
strates for other truncated or full-length copies, inducing genome
rearrangements. TE copies have been shown to give rise to new regu-
latory sequences, alternative splice sites, polyadenylation signals
(Marino-Ramirez et al., 2005), and new transcription-factor binding
sites (Polavarapu et al., 2008). TEs also enhance genome regulation
as, for example, when they give rise to microRNAs, which are able
to regulate gene expression (Hasler et al., 2007; Piriyapongsa et al.,
2007). Since TEs are widespread in the genome and have so many
different influences on gene regulation, several authors have sug-
gested that TEs may play a vital role in creating, remodelling and
regulating gene networks (McClintock, 1984; Feschotte, 2008). We
therefore hypothesize that bursts of TE activity may have profound
impacts on genome structure and gene regulation.
3. Bursts of TE transposition drive speciation
TEs have been observed in all sequenced genomes analyzed to
date, and comparative genomics gives us a broad insight into the
variability of TE content between genomes of different species. For
instance, TEs represent 85% of the maize genome (Schnable, 2009),
but only 14% of Arabidopsis thaliana's (The Arabidopsis Genome Ini-
tiative, 2000). Variations in genome size between closely related
species are often related to differences in the amount of TEs. For
instance, in the D. melanogaster species subgroup, larger genomes are
partly attributable to high TE-like sequence content, as estimated
from the amount of reverse transcriptase-related sequences deter-
mined by dot blot (Boulesteix et al., 2006). In cotton, differences in
genome size between species, ranging from 40 to 65%, have been
associated with a particular TE subfamily, the gypsy-like Gorge3 ele-
ment (Hawkins et al., 2006). Differences in the relative proportions
of TEs can also occur within a species, as observed for copies of several
TE families when counted in the euchromatic arms on polytene chro-
mosomes in natural populations of D. simulans (Vieira et al., 1999).
TE abundance, TE-derived genomic features and chromosomal re-
arrangements involving TE sequences are frequently lineage specific
and, therefore, suggest that TEs have contributed to the process of
speciation, either as a cause, or an effect (Marino-Ramirez et al., 2005;
Bohne et al., 2008). One should note that correlating TE transposition
consequences and speciation is rather tricky, since it is difficult to
determine the exact timing of TE bursts and natural species diver-
sification. We hypothesize that TE burst of transposition might induce
rapid speciation, but the debate is still open. A variety of factors such
as gene transfers and losses, mutations affecting “speciation genes”,
endosymbiotic interactions, antirecombination mechanisms during
meiosis, and introgression could also account for reproductive iso-
lation (Presgraves et al., 2003; Scannell et al., 2006; Lexer and Widmer,
2008; Lowry et al., 2008; Greig, 2009). In addition, an influence of TEs
on speciation apparently without transposition bursts was reported in
Fig. 1. General classification of eukaryote transposable elements. TEs are abundant and ubiquitous mobile sequences capable of jumping inside the genome. TEs are divided into two
major classes on the basis of differences in their transposition mechanisms: Class I Retrotransposons “copy and paste”through an RNA intermediate, whereas Class II DNA
transposons just “cut and paste”their own molecule. Autonomous retrotransposons harbor long terminal repeats in their ends (LTR) or not (LINE-like), and can be infectious agents
(endogenous retroviruses). Non-autonomous retrotransposons, such as SINEs, are dependent on autonomous elements to be “copied and pasted”in trans. The same dependency is
observed among DNA transposons, where MITEs need a full-length transposase coded by autonomous DNA transposons to be “cut and pasted”in trans. Full-length helitrons, recently
identified Class II DNA transposons, play an important role in exon shuffling thanks to their “rolling circle”replication mechanism. For a recent classification of eukaryote TEs, please
refer to Wicker et al., 2007. Boxes represent open reading frames, triangles are either inverted repeats (IR) in blue, or long terminal repeats (LTR) in green, and small blue arrows
correspond to duplicated insertion site representations. DDE elements: transposases carrying the aspartate (D), aspartate (D), glutamate and (E) motif. MITE: miniature inverted
repeated elements; ERV: endogenous retrovirus; LINE: long interspersed nuclear element; SVA: composite element composed of parts of SINE (short interspersed nuclear element),
VNTR (variable number of tandem repeats) and Alu repeats—the first box represents CCCTCT hexamer repeats; SINE red boxes indicate a diagnostic feature; Gag, Pol, Env: retroviral-
like proteins coded by TE open reading frames.
2R. Rebollo et al. / Gene 454 (2010) 1–7

some species. For instance, the formation of the recent invasive species
Spartina anglica through natural allopolyploidization was accompa-
nied by major structural and epigenetic remodelling (CpG methyla-
tion changes) in the vicinity of TEs (Parisod et al., 2009), but bursts of
transposition have not been detected (Baumel et al., 2002). Hetero-
chromatin, which is highly enriched in TEs and other repeats, also
seems to play a role in speciation, as observed by Ferree and Barbash in
Drosophila hybrids (Ferree and Barbash, 2009; Hughes and Hawley,
2009). Furthermore, bursts of transposition are not always associated
with rapid speciation. It should be kept in mind that Pand Ielements
have recently invaded natural populations of D. melanogaster, but no
speciation has been observed. Also, in a few rice strains, nearly 40 new
copies of the DNA transposon mPing are observed per plant generation.
For the present, the only consequence of this burst of transposition
has been slight transcriptional deregulation of a few genes that have
mPing copies inserted into their 5′flanking region. However, it is
interesting to note that a few of the genes containing mPing in their
flanking regions are salt- and cold-inducible as a result of the presence
of the DNA transposon, suggesting that a few insertions may play an
adaptive role (Naito et al., 2009). No massive restructuration of the
genome has been observed in rice despite the high rate of trans-
position, and no speciation seems to be happening in this species. We
hypothesize that in order for bursts of transposition to induce rapid
speciation, massive genome restructuring or mutations in “speciation
genes”have to occur. Several researchers have found examples of
concordant timing between bursts of transposition or massive TE
extinction and speciation (Table 1). While this short-review was in
revision, two bibliographic analyses of the punctuated equilibrium
theory, and the general impact of TEs in genomes were published, and
both reinforce the hypothesis that TEs may drive macroevolution via
bursts of transposition (Oliver and Greene, 2009; Zeh et al., 2009).
Significant TE activity is observed in several species, often during
periods of radiation, suggesting that massive speciation and massive
TE activity may be associated. The genetic distance between two
organisms is calculated as a function of their genetic divergence, so
every episode that creates divergence, such as lineage-specific trans-
position events, could contribute to the reproductive isolation of those
organisms. TE patterns that differ between individuals of the same
species, whether as a cause or a consequence of genetic differentiation,
may not only provide genetic markers for researchers, but also con-
stitute evidence of a speciation process occurring within the species
concerned (Esnault et al., 2008). For instance, significant TE insertion
site polymorphism can be observed in the Japonica and Indica cultivars
of rice, and accounts for 14% of their genetic differences (Huang et al.,
2008).
Since the exact evolutionary history of a species is difficult to
determine, interspecies crosses provide useful macroevolution study
models. Indeed, interspecies hybrids are classic examples of bursts of
transposition that have caused severe dysfunctions, and could poten-
tially induce rapid speciation (reviewed in Fontdevila, 2005; Micha-
lak, 2009)(Table 2). Three independent hybrids of the sunflower
species have a genome that is 50% larger than the parental lines as the
result of a massive TE transposition, and they are thought to have
undergone rapid speciation (in fewer than 60 generations in one case)
(Ungereret al., 1998, 2006). Also, in dosage-dependent crosses between
A. thaliana and A. arenosa (crosses where the amount of the maternal
and paternal genomes are variable, and so may be different), high
expression of the paternal A. arenosa Athila element in the hybrid is
correlated with seed lethality (Josefsson et al., 2006). Such obser-
vations are essential for understanding hybrid “compatibility”, since
A. arenosa and A. thaliana hybridization has been successful at least
once in nature (Jakobsson et al., 2006). In insects, D. buzzatii and
D. koepferae are still able to interbreed, and share common TE families
that are maintained in both genomes. Crosses between these two
species considerably induce the transposition of Osvaldo in the result-
ing hybrids, even though it is repressed in both parental genomes
(Labrador et al., 1999). In wallabies, interspecies hybrids contain vari-
able centromeres, composed of satellite repeats and newly replicated
TE copies (Metcalfe et al., 2007). McFadden and Knowles have de-
signed an algorithm in order to model evolution in asexual digital
organisms with or without TEs. They conclude that transposon-
mediated mutations were associated with punctuated bursts of rapid
evolution and appearance of new adaptive peaks, in contrast to the
stasis trap observed in organisms without transposons (McFadden and
Knowles, 1997). All these examples suggest that bursts of TE trans-
position occurring during hybrid speciation may induce important
karyotypic changes because of the ability of TEs to induce major chro-
mosomal rearrangements and ectopic recombination (Hedges and
Table 1
TE transposition bursts concomitant with radiation periods.
TE events/Species history References
Decreased L1 and SINE accumulation during emergence
of African apes (14–15 Mya).
Consortium (2002)
Generation of L1 subfamilies in less than 0.3 Mya
concomitant with intense speciation in
Rattus sensu stricto.
Verneau et al. (1998)
The timing of Lx family (L1 ancestral family)
amplification is close in time to the murine radiation.
Pascale et al. (1990)
Rapid speciation in the genus Taterillus (gerbil) occurred,
and massive transposition of TEs in new lineages
was observed.
Dobigny et al. (2004)
DNA elements were extremely active during the
Myotis radiation.
Ray et al. (2008)
DNA transposon transposition bursts are concomitant
with speciation events in pseudotetraploid salmonids
and occurred after genome duplication.
de Boer et al. (2007)
Acquisition and consequent transposition of an endogenous
retrovirus element in Entamoeba histolytica, and lineage
specific enrichment in TEs might affect speciation
and pathogenicity.
Lorenzi et al. (2008)
Table 2
Hybrid analysis: epigenetic remodelling and TE activation.
Experimental conclusions References
Mus musculus and M. caroli crosses induce retroelement
hypomethylation on chromosome 10, the substrate
of double minute chromosome formation in
interspecies hybrids.
Brown et al. (2008)
Intraspecific crosses of D. melanogaster can result in
hybrid dysgenesis, associated with mobilization of
Por Ielements, dependent on rasiRNA production in
the germinal cell line and causing several
abnormalities (such as female sterility).
Brennecke et al. (2008)
Crosses between D. buzzatti and D. koepferae activate
Osvaldo copies in the hybrid.
Labrador et al. (1999)
Interspecific macropodid hybrids (Macropus rufogriseus
and M. agilis) present centromeric instability due to
TEs and satellite replication, probably inducing
karyotypic isolation from the parental species.
Metcalfe et al., 2007
Genome-wide hypomethylation and centromeric
expansion, due to TE activation, are observed in
M. eugenii or Wallabia bicolour hybrids.
O'Neill et al., 1998
In A. thaliana and A. arenosa dosage-dependent crosses,
the usually silenced paternal Athila elements are
activated concomitantly with the deregulation of
polycomb complex-dependent gene regulation.
Josefsson et al. (2006)
Wheat allotetraploid formation is accompanied by TE
activation, DNA methylation and gene expression
alterations.
Kashkush et al., 2002
Helianthus annuus and H. petiolari hybrids have a
genome 50% larger than parental individuals due
to TE amplification.
Ungerer et al. (1998),
Ungerer et al. (2006)
DNA introgression in Zizania latifolia causes TE activation
through modifications in DNA methylation and
morphological deviations from the primordial line.
Note that de novo stable silencing of TEs is observed in
the introgressed lines.
Liu and Wendel (2003)
3R. Rebollo et al. / Gene 454 (2010) 1–7

Deininger, 2007; Weil, 2009). In this way, TE mobilization can result
in novel phenotypes followed by the ecological isolation of micro-
populations, which are the components required for rapid and diver-
gent evolution.
Both transcription and transposition activities of TEs are controlled
via a variety of mechanisms. The expression of TEs is dependent on
the presence of transcription factors, as illustrated by the evolution
of the L1 lineage in humans. Indeed, the recruitment of regulatory
regions in new L1 subfamilies harboring new transcription-factor
binding sites is essential for L1 expression (Khan et al., 2006). Fur-
thermore, cellular inhibitors may influence TE transposition post-
transcriptionally, as has been observed for some members of the
APOBEC family, which are capable of reducing HERV-K infectivity
(50 fold) (Lee and Bieniasz, 2007), and block Alu transposition in a
manner independent of ORF1p L1 (Hulme et al., 2007). Moreover,
transposition of mobile elements induces DNA breaks, suggesting
that an interaction occurs between the host DNA repair machinery
and TEs. ERCC1-XPF heterodimers are implicated in DNA repair pro-
cesses and limit L1 insertion (Gasior et al., 2008). Apart from cellular
inhibitors and transcription factor dependency, TEs are also transcrip-
tionally and post-transcriptionally regulated through epigenetic path-
ways (Lisch, 2009). However, we know that epigenetic mechanisms
are labile in response to environmental changes, and so TEs may
occasionally escape silencing, and in some cases could cause genome
rearrangements. In order to understand how speciation occurs as a
result of transposition bursts, it is therefore essential to understand
epigenetic reprogramming.
4. Epigenetic reprogramming of TEs
Epigenetic regulation of TEs involves interdependent pathways,
such as chromatin remodelling factors, DNA methylation and non-
coding small RNAs (Lisch, 2009; Obbard et al., 2009)(Table 3 for an
overview of TE epigenetic regulation). In rice, for instance, specific
mutants of histone H3K9 methyltransferase induce DNA demethy-
lation of Tos17 (copia-like retrotransposon) and, consequently, lead
to transposition (Ding et al., 2007). In plants, RNA-dependent DNA
methylation (RDDM) of TEs and genes is often observed. This is re-
versible, since it is dependent on the presence of small interfering
RNAs (Matzke et al., 2007). Recent investigations have highlighted
the central role of RNA in controlling TE activity: such a system was
probably present in a common eukaryote ancestor as it is well con-
served between species; and it may act as an immunological system
against non-self RNAs (Obbard et al., 2009). Also, small RNAs allow
for target specificity of DNA methylation or histone modification in a
given sequence. For instance, epigenetic instability in long-term cul-
tured cells of A. thaliana evolves into the hypomethylation of specific
TEs and subsequent activation (Tanurdzic et al., 2008). Indeed, Athila
or copia elements are hypomethylated, regardless of their location,
whereas no change is observed for gypsy class elements (Tanurdzic
et al., 2008). Such specificity is possibly due to the fact that siRNAs
are produced differently in TE families subjected to stress of this type,
varying from 21 nt and 24 nt for hypomethylated activated TEs, but
with only 24 nt for silenced gypsy class elements (Tanurdzic et al.,
2008).
The TE epigenetic regulation system is in fact rather efficient.
It is general in nature, because the TE families capable of invasion
are multiple and divergent but, at the same time, it also appears to
be specific, and targets single TE families through sequence-specific
small RNAs. Each pathway in the epigenetic regulation of TEs seems,
therefore, to be both essential and extremely rigorous. Naturally the
question arises as to how TEs can possibly invade a genome if they are
trapped in an inviolable prison. In fact, we know that TEs often do
transpose at a very low rate, suggesting that the prison is after all,
somewhat permeable. Indeed, it has recently been suggested that
small RNAs can be linked with the total or partial silence of elements,
as observed in Drosophila hybrid dysgenesis. Indeed, intraspecies
Drosophila crosses may cause hybrid dysgenesis of Pand Ielements,
resulting in very seriously deleterious effects, such as female steril-
ity or chromosomal abnormalities (Bucheton et al., 1984; Castro and
Carareto, 2004). In these crosses, individuals of the same species have
different amounts of TEs since one of the parents has an “empty”
genome. A deficit in a small interfering RNA (piRNA) in the maternal
gamete allows originally silenced TEs to transpose in the hybrids
(Brennecke et al., 2008; Chambeyron et al., 2008).
The study of natural populations and the observation of the nat-
ural variability that exists in epigenetic host control can explain
TE-induced macroevolution. Epigenetic variation in hybrids, in allo-
polyploid species, and in single individuals could arouse the TEs,
induce a burst of transposition and, as described above, increase kar-
yotypic changes followed by ecological isolation. TE epigenetic regu-
lation has been reported both in somatic tissues (Barbot et al., 2002;
Malone et al., 2009) and in germline tissues (Malone et al., 2009). Both
types of regulation can influence population behavior by creating
potentially heritable phenotypic variations. Variation in TE epigenetic
regulation has been observed, for instance, in the LINE-like element
Sadhu, that displays epigenetic variation (DNA methylation and differ-
ent silencing states) in three different A. thaliana ecotypes (Rangwala
et al., 2006). Other epialleles, or differences in the epigenetic regu-
lation of a given sequence in different tissues and/or individuals
belonging to the same population, have been reported, mostly in
plants and mice. However, further progress in population epigenetics
is still necessary, along with ecological epigenetic studies, if we are
fully to understand natural population variation in epigenetic regula-
tion (Bossdorf et al., 2008; Johannes et al., 2008; Richards, 2008). TE
Table 3
General view of TE epigenetic regulation.
Histone modifications Position effect variegation (PEV) is the mechanism behind
variation in the transcription of a given gene, and is
correlated to its chromatin localization. Mutations in
Su(var) genes responsible for such variegation are often
accompanied by TE amplification. The major function of
this gene family is to post-translationally modify histone
N terminal ends. Usually histone methylation in lysine
residues (H3K9me, H3K27me, and H4K20me) typically
occurs in a closed chromatin conformation, in contrast to
the acetylation of histones and methylation in H3K4,
which are often observed in open chromatin structures.
TEs are closely associated with repressive marks, like
H3K9me3 in humans, H4K20me3 in Drosophila and
H3K9me2 in plants.
DNA methylation In plants and mammals, DNA methylation plays an
important role in silencing TEs. In insects,
DNA methylation is observed as a silencing process
in genes and TEs.
Non-coding RNAs Post translational gene silencing (PTGS) via small
interfering RNAs (siRNA) processed by the AGO/DICER/
RISC complex is another mechanism that can be used to
silence TEs. Indeed siRNAs derived from TE copy
transcripts can target full-length and putatively active
TE transcripts, thus preventing TE transposition.
Piwi related RNAs (piRNAs or rasiRNAs, standing for
repeated associated small interfering RNAs) in Drosophila
are processed via the Piwi/Aub/AGO3 pathway, are
24–30 nt and are known to silence TEs in the germline,
whereas endo-siRNA (endogenous small interfering RNAs)
processed by DICER2/AGO2 are 21 nt, and are capable of
somatic silencing TEs. Germinal and somatic silencing are
therefore possible thanks to non-coding RNAs. However,
the presence and the transcription of a TE copy in the
genome are essential to engage PTTES (post translational
transposable element silencing). The idea that this
constitutes an immune system is therefore appropriate,
since having non-coding RNAs of a given TE family will
protect the genome from further invasions.
4R. Rebollo et al. / Gene 454 (2010) 1–7

epigenetic regulation is, therefore, a variable and flexible mechanism
that can induce massive TE transposition in the germline, and conse-
quent chromosomal rearrangements.
The gibbon species has rapidly accumulated chromosomal rear-
rangements and, hence, offers an interesting model for karyotypic
evolution and speciation. Carbone et al. recently reported an example
of differences in the epigenetic regulation of Alu elements in humans
and gibbons that is associated with breakpoints between the species
(Carbone et al., 2009). They observed that CpG content was higher
in the gibbon Alu elements near the breakpoints (typical of active
elements), and that these elements were undermethylated relative
to human Alu.Alu elements present in the breakpoints are probably
active and responsible, in part, for the rapid chromosomal remodel-
ling in the gibbon. The authors propose that “the association between
undermethylation and chromosomal rearrangement in gibbons sug-
gests a correlation between epigenetic state and structural genome
variation in evolution”.
Conjugating two different genomes in the same organism, as
in hybrids or in allopolyploids, may require significant adaptations
of all the regulatory mechanisms, including TE epigenetic regula-
tion (reviewed in Michalak, 2009)(Table 2). In wallabies, interspecies
crosses cause a burst of transposition of a retrotransposon, together
with genome-wide hypomethylation (O'Neill et al., 1998). Such a burst
of transposition targets a single parental genome, and results in ex-
tended centromeres, suggesting rapid karyotype differentiation from
the parents (O'Neill et al., 1998). The authors also analyzed some other
natural crosses, and found that hypomethylation of the hybrids was
always observed as de novo chromosomal changes. In allopolyploidi-
zation, TE transposition may also be concomitant with genome-wide
epigenetic changes (Liu and Wendel, 2003). These examples show
how genome remodelling could occur after epigenetic variation in
TE copies. However, we need to identify the causes of genome-wide
epigenetic modifications and subsequent TE activation. Interspe-
cies crosses induce genomic stress, i.e. changes in genomic stability
(chromatin changes, density of repeats…) and organization (DNA
recombination, TE replication, retroposed or duplicated genes…), that
could indeed have an impact on epialleles and provoke TE activation.
Genome-wide epigenetic changes might play a role in genome adap-
tation to environmental changes. One can readily imagine that TE
arousal occurs due to epigenetic changes, and that these changes orig-
inate in one individual in response to specific environmental changes.
The ecological outcomes of TE mobilization due to environmental
changes may be numerous, including things such as survival of the
host, increase of host fitness, micro-population isolation etc. The sub-
sequent spread of these factors within populations could lead to
sexual isolation and speciation.
5. The environment induces epigenetic reprogramming
Several studies have demonstrated that modifications in the envi-
ronment can induce epigenetic modifications and, therefore, tran-
scription state changes (Jaenisch and Bird, 2003). Such transcriptional
changes are a source of phenotypic variability that may be exploited
by organisms to increase the “adaptative potential”of the host. Indeed,
diet changes, temperature variation, stress etc. all have an impact
on gene regulation (Waterland and Jirtle, 2004; Cropley et al., 2006;
Gibert et al., 2007; Chinnusamy and Zhu, 2009). In addition, diet
changes, temperature variations, stress etc. could all affect TE trans-
position (El-Sawy et al., 2005; Hashida et al., 2006; Ebina and Levin,
2007; Cho et al., 2008). Consequently, activation of TEs could result
from the relaxation of epigenetic control induced by environmental
changes.
There is a huge amount of literature relating the activation of
TEs to environmental stress, but only a few examples suggest a link
between environmental epigenetic instability and the activation of
TEs. Early nutrition has an impact on the epigenetic regulation of
TEs, especially via DNA methylation, as reviewed by Waterland and
Jirtle, 2004. The agouti gene controls hair color in mice (brown in wild
type), and the insertion of an IAP retrotransposon in the first exon
induces ectopic and variable expression of agouti. LTR from IAP ele-
ments are regulated by DNA methylation, which varies between
individuals. Dietary supplementation (with methyl donors) shifts the
phenotype to the wild type brown colour, which is indicative of higher
DNA methylation in the IAP element (Waterland and Jirtle, 2003).
In D. melanogaster, both heat treatment and aging induce the tran-
scription of older heterochromatic I copies and, hence, the production
of small interfering RNAs (rasiRNA) that repress active I elements in
the germline (Dramard et al., 2007). DNA methylation of L1 and Alu1
elements is decreased in individuals exposed to the pollutant benzene
(Bollati et al., 2007) and, similarly, benzo(a)pyrene increases retro-
transposition of L1 elements in HeLa cells (Stribinskis and Ramos, 2006).
In mice, a long-term peroxisome proliferating diet induces hypomethy-
lation of satellites, IAP and L1/L2 elements (Pogribny et al., 2007).
6. Conclusion
The fact that TE copies are subject to epigenetic regulation has two
main consequences: 1) the environment can have a direct influence
on TE activity through epigenetic instability and 2) TE sequences
are present in the host genome in a “harmless”state. Since bursts of
transposition have been observed in several species it is tempting to
suggest that their defense systems have, at least temporarily, broken
down. However, this failure is transient, and the host may rapidly
silence any de novo TE copies produced. Although the benefit is not
immediate, transposition might have a long term advantage. Indeed,
transposition bursts have numerous consequences, resulting in a re-
newal of genetic diversity, which is the major prerequisite for genome
evolution and selection to occur. Genetic diversity is fundamental for
gene networks to be renewed, allowing new species to emerge. Each
environmental change indirectly creates an increase in host genetic
variability, which means that selection can act over a larger repertoire
of genetic information. Epigenetic instability of TEs would lead to
significant genetic variability, and the subsequent selection of the best
adapted organism.
Acknowledgements
Owing to space limitations, we sincerely regret the omission of
many outstanding publications in this field. We thank Dr. M. Fablet,
Dr. D. Reiss and two anonymous reviewers that contributed signifi-
cantly to improve the manuscript. We thank Monika Gosh for cor-
recting the English of this article. This work was supported by ANR–09-
BLANC–0103-01, FINOVI and CIBLE2008 (Région Rhône Alpes).
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