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Journal of Heredity 2009:100(5):648655doi:10.1093/jhered/esp065Advance Access publication August 7, 2009

The American Genetic Association. 2009. All rights reserved.For permissions, please email: [email protected].

Transposable Elements and Factors

Influencing their Success in Eukaryotes

ELLEN J. PRITHAM

Department of Biology, University of Texas, Arlington, 501 S. Nedderman Drive, Arlington, TX 76019.

Address correspondence to Ellen J. Pritham at the address above, or e-mail: [email protected].

Abstract

Recent advances in genome sequencing have led to a vast accumulation of transposable element data. Consideration of the

genome sequencing projects in a phylogenetic context reveals that despite the hundreds of eukaryotic genomes that havebeen sequenced, a strong bias in sampling exists. There is a general under-representation of unicellular eukaryotes anda dearth of genome projects in many branches of the eukaryotic phylogeny. Among sequenced genomes, great variation ingenome size exists, however, little difference in the total number of cellular genes is observed. For many eukaryotes, theremaining genomic space is extremely dynamic and predominantly composed of a menagerie of populations of transposableelements. Given the dynamic nature of the genomic niche filled by transposable elements, it is evident that these elementshave played an important role in genome evolution. The contribution of transposable elements to genome architecture andto the advent of genetic novelty is likely to be dependent, at least in part, on the transposition mechanism, diversity, number,and rate of turnover of transposable elements in the genome at any given time. The focus of this review is the discussion ofsome of the forces that act to shape transposable element diversity within and between genomes.

Key words: gene mapping, genome evolution, transposable element

Despite great variation in genome size, little difference inthe total number of cellular genes is observed amongeukaryotes (Gregory 2005; Feschotte and Pritham 2007b).In many instances, the cellular genes may represent justa small sliver of the total genomic space. These genic regionsare the most stable part of an organisms genome, largelydue to purifying selection acting to preserve gene function.For many eukaryotes, the remaining genomic space isextremely dynamic and predominantly composed ofa menagerie of populations of transposable elements(TEs) (for review Kidwell and Lisch 2001; Craig et al.2002). The TEs can be viewed as genomic squatters,shacking up in the genome without providing any directbenefit to the host. TE persistence is then a reflection of

both the ability to replicate faster than the host cell and ofthe balance between TE reinfection through outcrossing,horizontal transfer and TE loss through excision, sequenceerosion, selection and drift (Craig et al. 2002). Given thedynamic nature of the genomic niche filled by TEs, it isevident that these elements have played an important role ingenome evolution (Kidwell and Lisch 2002; Wessler 2006;Feschotte and Pritham 2007a). The contribution of TEs togenome architecture and to the advent of genetic novelty islikely to be dependent, at least in part, on the transpositionmechanism, diversity, number and rate of turnover of TEsin the genome at any given time. The focus of this review is

the discussion of some of the forces that act to shape TEdiversity within and between genomes.

Transposition Mechanisms and TE

Classification

TEs are classified based on the nature of the transpositionintermediate (RNA or single or double-stranded DNA[ssDNA or dsDNA]), their structural features, and byhomology to known elements (Feschotte and Pritham2007a; Wicker et al. 2007). Broadly, TEs are divided into 2classes based on whether the transposition intermediate isRNA (class 1) or DNA (class 2) (Figure 1). Class 1 TEs or

retrotransposons all require reverse transcriptase to copytheir RNA into DNA and can be subdivided into 3 groupsbased upon mechanism of integration (Figure 1) (for reviewEickbush and Malik 2002). The reverse transcriptaseencoded by each of these groups shares 7 blocks ofconserved sequences suggesting that they are related bydescent and share a common ancestor, although in the verydistant past (Xiong and Eickbush 1990). The diversity ofstructures and integration mechanisms of retrotransposonsis a testament to their ability to adapt and change. The longterminal repeat (LTR) and the tyrosine recombinase (YR)retrotransposons are both flanked by LTRs but they differ

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in the mechanism of integration (for review Cappello et al.1984; Eickbush and Malik 2002; Goodwin and Poulter 2004;Poulter and Goodwin 2005). The LTR retrotransposonsutilize an integrase, which is evolutionarily related to thetransposase encoded by cut-and-paste DNA transposons,

whereas the YR retrotransposons utilize a tyrosine recom-binase. The non-LTR and probably also Penelope-likeretrotransposons transpose via a process termed target-primed reverse transcription (TPRT) and integration ismediated by either an apurinic/apyrimidinic or a restriction-like endonuclease (Eickbush and Malik 2002; Evgenev and

Arkhipova 2005).Class 2 or DNA transposons transpose via a DNA

intermediate. Classic DNA transposons are excised asdsDNA intermediate and reintegrated elsewhere in thegenome (for review Feschotte and Pritham 2007a). Thesecut-and-paste transposons are exemplified by a relativelysimple structure typically consisting of a single ORF,

encoding a transposase, flanked by terminal inverted repeats(TIRs) and they are usually less than 5 kb in size (Figure 1).Helitrons, which represent a second major subclass of DNAtransposons, are most likely mobilized as ssDNA inter-mediates through a replicative, rolling-circlelike mecha-nism. They encode a putative protein with a central domainhomologous to the rolling-circle replication proteinsencoded by rolling-circle genetic elements (e.g. plasmids,phages) and a C-terminal domain related to the PIF1 groupof DNA helicases. PlantHelitronsalso encode 13 additionalputative proteins homologous to ssDNA binding proteins

(for review Kapitonov and Jurka 2006, 2007; Feschotte andPritham 2007a). Finally, Mavericks represent a third subclassof DNA transposons recently identified in a wide range ofeukaryotes. The Mavericks are distinguished from the otherDNA transposons by their large size (ranging between 9 and22 kb) and extensive coding capacity (920 open reading

frames [ORFs]), which include a gene encoding a viral-likeDNA polymerase (Figure 1) (Feschotte and Pritham 2005;Kapitonov and Jurka 2006; Pritham et al. 2007). Mavericksalsoencode a retroviral-like integrase and therefore their trans-position cycle involves integration of a dsDNA intermediate.

TEs that utilize unknown transposition mechanisms are beingdiscovered and described at an unprecedented rate due to the

tremendous abundance of genome data now available forscrutiny (Kapitonov and Jurka 2001; Goodwin et al. 2003;Feschotte 2004; Feschotte and Pritham 2005; Feschotte andPritham 2007a; Pritham et al. 2007).

The Distribution of TEs in the Tree of Life

The genomes of hundreds of eukaryotes have been or arein the process of being sequenced, providing theopportunity to analyze a vast quantity of TE data.

However, it should be noted that there is a strong biasin this data set toward animals and fungi (e.g., opistho-konts) and to a lesser degree apicomplexan (which includemalaria parasites) and plant genomes. This bias is evident

when the number and incidence of projects are consideredin a phylogenetic context (see Figure 2). Surprisingly, manybranches of the eukaryotic phylogeny have yet to besampled. This bias in sampling makes difficult, and shouldprobably preclude, any broad generalizations about TEdiversity and distribution in eukaryotes. Surveys of the TEpopulations within the sequenced genomes have made it

clear that TEs are indeed widespread and persistent entitiesin metazoans, fungi, and plants. In addition, a positivecorrelation is often seen between genome size and TEcontent in these genomes (Feschotte and Pritham 2007b).However, the distribution and abundance of TEs inunicellular eukaryotic organisms is far less understood,

Figure 1. TEs are broadly classified into 2 classes. Class 1 retrotransposons move using an RNA intermediate, and class 2 the

DNA transposons utilize a DNA intermediate. The presence and orientation of repeated DNA structures flanking or within the

TEs are indicated by arrows. The black arrows are TIRs. The gray arrows are direct repeats. The striped arrows indicate a repeated

sequence or palindrome within the DNA. The gray-hatched boxes indicate the proteins encoded by autonomous TEs, the number

of ORFs is so indicated.

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hampered by the paucity of sequencing projects andtherefore the scarcity of data, as well as a less systematic

and careful scrutiny of the sequenced genomes.

Genome Sequence Comparisons Reveal

Patterns in TE Diversity

Examination of complete genome sequence data allows theanalysis of an organisms genome at a single point in time.Dramatic differences between the success of retrotranspo-sons and DNA transposons are revealed when surveys ofgenome sequence data are undertaken (Figure 3). Variationoccurs in terms of total number, composition, and locationof TEs within and between genomes. For example, both thehuman and mouse genomes are dominated by retrotrans-posons (Lander et al. 2001; Waterston et al. 2002), whereasDNA transposons have been relatively more successful inthe genome of the nematode Caenorhabditis elegans (Consor-tium 1998). In the budding and fission yeast genomes, onlya few hundreds LTR retrotransposons are found, despite a 1billion years of divergence (Hedges 2002). Are these

patterns purely stochastic or are they the result ofevolutionary forces acting to influence TE success and

shape genome architecture? If TE diversity and success wasattributed solely to random gain and loss, than given therapid turnover of TEs, no trends should be apparent. Giventhe rapid turnover of TEs and a constant rate of TEintroduction and amplification, if stochasticity was the majordeterminant in shaping these patterns than no trends shouldbe apparent. However, some trends in TE composition doappear to be conserved. For example, the human, macaque,mouse, rat, and dog genomes share a strikingly similarpattern of TE composition, despite continuous andextensive lineage-specific TE activity (Pace and Feschotte2007). Similarly, analysis of the sequenced genomes of 12

Drosophila species separated by up to 40 million years ofevolution shows that retrotransposons predominate in allthese species, whereas DNA transposons consistentlyrepresent less than 20% of the total TE content (Clarket al. 2007). What does the conservation of TE compositionbetween species tell us, and can inferences be made aboutthe history of a species when a difference in pattern isobserved?

Figure 2. The distribution of eukaryotic genome projects mapped in a phylogenetic context. A survey was undertaken of

eukaryotic genomes with sequencing projects completed or underway. Both the presence and abundance, of genome sequencing

projects in a specific phylogenetic branch is indicated by a gray circle. The size of the circle is meant as a rough indication of total

number of projects. The smallest circle indicates a single project and the largest indicating.50 projects. A 5 supergroup Plantae,

B 5 supergroup Excavate, C 5 supergroup Rhizaria, D 5 supergroup Unikonts, E 5 supergroup Chromalveolates (phylogeny

redrawn from Keeling et al. 2005).

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Forces that Influence TE Diversity can be

Subdivided into Three Groups based on

the Scale at which They Act: Molecular,

Genetic, and Environment

Molecular Properties of the TE

Molecular properties of the TE can function to influenceTE activity and therefore accumulation in genomes, as wellas the propensity of TEs to be vertically or horizontallytransmitted. Some examples of molecular factors includetransposition mechanism (Eickbush and Malik 2002), thepattern and timing of transposition (which can be influencedby tissue and temporal specific promoter regions oralternative splicing) (Rio 2002), TE autoregulation (Rio2002), targeting (Devine and Boeke 1996; Eickbush andMalik 2002); (for review Lesage and Todeschini 2005) andinfectivity (or the ability to move cell to cell or betweenorganisms) (Malik et al. 2000). The non-LTR retrotranspo-sons provide an excellent example of how the mechanism oftransposition can influence both the ability of TEs tocolonize specific genomic niches and their ability topropagate horizontally, as well as limit the selective impactof new insertions. For non-LTR retrotransposons, in-

tegration is coupled to reverse transcription of the mRNAin a process termed TPRT (Christensen and Eickbush2005). Due to the inherent instability of RNA it is probablethat the DNA form of the retrotransposon would be morelikely to move horizontally than the RNA itself. Because theDNA is integrated directly into the nuclear genome, as it isreverse transcribed from RNA, the window of opportunityfor horizontal movement appears to be temporally narrowfor these elements (for review Eickbush and Malik 2002). Inaddition, for most non-LTR elements the TPRT processresults in many copies that are truncated in the 5#-end, withthe promoters being lost and further propagation inhibited.

These dead on arrival copies are typically the mostabundant product of TPRT. Thus, for a successfulhorizontal transfer event to occur, a rare complete non-LTR element would have to be transferred. Also, many non-LTR retrotransposons have target-site specificity, whichminimizes the genomic space where integration can occur.For example, R2 and R4 elements target the 28S genes andCRE and NeSL are targeted to splice-leader sequences(Burke et al. 1987; Teng et al. 1995; Malik and Eickbush2000) (and for review Eickbush and Malik 2002). Both

TPRT and site-specific targeting are expected to reduce thepotential of non-LTR retrotransposons to be movedbetween species by horizontal transfer. On the other hand,targeted integration into other highly repeated sequencesminimizes the deleterious effects of these elements, whichfacilitates their vertical persistence (Malik et al. 1999).Indeed, in some cases non-LTR retrotransposons have evengone extinct in a number of mammals (Casavant et al. 2000;Grahn et al. 2005; Rinehart et al. 2005; Cantrell et al. 2008).

In contrast, horizontal movement of both DNA trans-posons and LTR retrotransposons appears to be morefrequent. Recurrent waves of horizontal transfer of DNAtransposons are thought to explain the diversity of recentlyactive DNA transposons in the genome of the little brownbat (Myotis lucifugus) (Ray et al. 2008). The diversity of TEs in

M. lucifugus deviates dramatically from the pattern observedin the genomes of other well-studied mammals where norecent DNA transposon activity has been reported andretrotransposons predominate (Pritham and Feschotte 2007;Ray et al. 2007, 2008).

The compact eukaryotic genomes, like those of theyeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe,provide insight into how the ability to target specificgenomic regions has allowed LTR retrotransposons topersist in these highly compact, gene-rich genomes andhighlights the complex interplay between molecular prop-erties of the TE and genetic properties of the genome. Bothgenomes are small (;12.5 Mb) and have limited intergenicspace, proving a hazardous terrain for TE insertion. TEsthat target specific sites in the genome, in effect narrow thescope of their mutagenic impact to these specific genomiclocales. The Ty1 and Ty3 retrotransposons of S. cerevisiaetarget the upstream of genes transcribed by RNA poly-merase III (Kim et al. 1998). For example, 90% of Ty1elements are within the 750 bp flanking a tRNA gene. Ty5retrotransposons, which naturally inhabit the genome of

Figure 3. Variation of TE composition across genomes. For

each species, the relative proportion of RNA and DNA TEs

was calculated. The data were compiled either from the

corresponding papers reporting draft genome sequences or

from the following sources: nematode C. Feschotte, personal

communication; rice (Jiang et al. 2004) and N. Jiang, personal

communication; Entamoeba(Pritham et al. 2005); Giardia lamblia(Arkhipova and Morrison 2001); Trichomonas vaginalis (Pritham

et al. 2007); and Ellen Pritham (unpublished data). The species

are Hs 5 Homo sapiens, Mm 5 Mus musculus, the nematode,

Caenorhabditis elegans, Dm 5 Drosophila melanogaster,

De 5 Drosophila erecta, Ag5 Anopheles gambiae, Aa 5 Aedes

aegypti, Ed 5 Entamoeba dispar, Eh 5 E. histolytica, Ei 5 E.

invadens, Em 5 E. moshkovskii, Sc 5 Saccharomyces cerevisiae,

Sp 5 Schizosaccharomyces pombe, At5 Arabidopsis thaliana,

Os 5 Oryza sativa japonica, Gi 5 Giardia lamblia,

Tv5 Trichomonas vaginalis.

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S. paradoxus, actively target the silent chromatin located atthe mating loci and near the telomeres (Zou et al. 1996). InS. pombe, the Tf12 elements have evolved a differenttargeting strategy whereby they integrate upstream of RNApolymerase II transcripts (Leem et al. 2008). Remarkably,the targeting strategy of all these retrotransposons hasevolved independently and is mediated by direct interactionsbetween host factors and the integrase proteins encoded bythe elements (Gao et al. 2008). This illustrates how TEs canestablish intimate and long-term relationships with theirhosts. Targeting potential does not seem to be a universalfeature of LTR retrotransposons and the location andmechanism for targeting differs among elements suggestingthat this intrinsic property has evolved repeatedly atdifferent evolutionary times.

Ecological Influences on Host TE Populations

The ecology of the host population and environment arealso likely to play an indirect but important role in thesuccess of TEs within genomes. Examples of these forcesinclude parasite load, environmental quality, resourceavailability, and competition. These ecological componentscan affect the breeding system, effective population size ofthe host, and exposure to vectors of horizontal transfer

which in turn influence the ability of TEs to proliferate andfix in a genome (Wright and Schoen 1999; Arkhipova andMeselson 2000; Lynch and Conery 2003). Of course, theseforces are not mutually exclusive and they are ofteninterconnected. For example, effective population size willaffect TE success directly by determining the likelihood ofnew insertions to reach fixation within a population and alsoindirectly by influencing other features of genome organi-zation and gene structure which determines whether aninsertion is likely to be detrimental or largely neutral for thefitness of the host (Lynch 2007). In addition, none of thesefactors are static with respect to time. Sex and recombina-tion have been postulated to be of major import in thesuccess of TEs in populations, and their influence has beeninvestigated in a number of different systems (Arkhipovaand Meselson 2000; Wright et al. 2003; Valizadeh andCrease 2008). Because TE insertions do not in general havea selective advantage they will be eventually lost over time

when sequence erosion and drift leads to a higher rate ofloss than birth or reinfection occurs through zygoteformation and horizontal transfer. Therefore it is expectedthat strictly asexual organisms will eventually be purged of

TEs. The bdelloid rotifers are a widely diverged group ofanimals where meiosis, males, and sex have never beenobserved. Studies investigating TE distribution and diversityin the genome of bdelloid rotifers reveal the presence ofa diverse assortment of DNA transposons and 2 families ofretrovirus-like elements, but an apparent lack of non-LTRretrotransposons (Arkhipova and Meselson 2000; Arkhipovaand Meselson 2005). Because DNA transposons andretroviruses, but not non-LTR retrotransposons, arethought to be prone to HT, this biased TE composition

was interpreted to support the theory that the lack of sex

indeed result in a general purging of TEs that cannot bereintroduced horizontally. Recent studies from the samegroup show that bdelloid rotifers have been subject torecurrent and massive horizontal transfer events, a findingthat may lend support to the explanation that the biased TEcomposition of their genomes is driven by the presumedasexuality of these organisms.

However, breeding systems do not seem to be anoverriding force in determining the diversity of TEs in otherorganisms. A survey of TEs in the ;20-Mb genomes of 4related Entamoeba species reveals that a diverse set of TEs(including retrotransposons and DNA transposons) con-tribute to between 5% and 8% of these genomes (Prithamet al. 2005). Entamoebaare unicellular amoebas that are eitherparasitic or free living and have a genome size of;20 Mb.

They reproduce asexually using binary fission and no sexualstage has even been observed, however, a cryptic sexualstage has not been formally ruled out. Yet different speciesof Entamoeba display dramatic variation in the type andsuccess of TEs populating their genomes. The closelyrelated extracellular, human parasites E. histolytica and

E. dispar genomes are packed with non-LTR retrotranspo-sons, whereas the genomes of the reptilian parasite,

E. invadens and the free living, E. moshkovskii have relativelyfew retrotransposons but host a wide diversity of DNAtransposons. No evidence of horizontal transfer wasdetected and phylogenetic analysis suggested that many ofthe TE lineages detected in these 4 species were present intheir common ancestor and most likely have been verticallyinherited. Demographic factors like population bottlenecksare expected to play a role in TE diversity both due toalterations in the efficacy of natural selection as well as theimpact of genetic drift in changing genetic diversity. Inaddition, it has been suggested that the mechanism oftransposition that leads to differential accumulation, such asis seen between retrotransposons (copy and paste) andDNA transposons (cut and paste) predisposes them todifferential success in an effective population size dependentmanner (Lynch and Conery 2003). Therefore, it may be that

E. moshkovskii and E. invadens have an effective populationsize sufficient to allow for DNA transposon accumulation,

whereas E. dispar and E. histolytica do not. Indeed, studieshave revealed that E. dispar and E. histolytica have gonethrough recent population bottlenecks (Ghosh et al. 2000).It is clear that a single intrinsic or extrinsic factor is notsufficient to explain TE diversity within a genome.

Are TEs Ubiquitous Components of

Eukaryotic Taxa?

The publication of several, unicellular eukaryotic genomepapers fail to report the presence of TEs in the respectivegenomes. Included in the list are the red alga Cyanidioschyzonmerolae, supergroup Plantae (16.5 Mb) Matsuzaki, Misumiet al. 2005, the Apicomplexans: Babesia bovis (9.4 Mb)Brayton et al. 2007 Cryptosporidium hominis(9.2 Mb) (Xu et al.2004), C. parvum (9.09 Mb) Abrahamsen et al. 2004,

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Plasmodium falciparum(23.27 Mb) Gardner et al. 2002, P. yoelliyoelli (20.17 Mb) Carlton et al. 2002 and Thelieria parva (8.35

Mb) Bishop et al. 2005 and the Unikont, Encephalitozooncuniculi (2.8 Mb) (Katinka et al. 2001). However, becausemost of these organisms are only distantly related to themajority of the eukaryotic genome sequences available in thedatabases, the lack of reported TEs in some cases mightreflect an inability to identify TEs based on sequencehomology to known TE types. Closer inspections of thesegenomes with de novo repeat identification software (forreview Feschotte and Pritham 2007b) might reveal thepresence of novel TE families, that have never beenpreviously described or are only distantly related to known

TEs. Nonetheless, it is noticeable that these genomes are allextremely small, ranging in size between 2.8 and 23.27 Mb.

Among unicellular eukaryotes, there is a strong correlationbetween genome and cell size. The seeming dearth of TEsidentified in these genomes may provide insight into thepopulation demography of these species. For example, thelack of TEs coupled with the relatively small genome sizemight indicate that natural selection is effectively removing

TEs from these genomesperhaps due to a selectivepressure to maintain cell size and therefore genome size.

Another, not mutually exclusive explanation for the lack ofdetectable TEs in these species would be that a TE-depletedgenome was inherited from a common ancestor that was itself

TE free. For example, perhaps the common ancestral genomeof all Apicomplexa was TE free (of the 6 Apicomplexangenomes published, no convincing reports of TEs have beenmade), due to a single demographic accident. However, evenif the genome of the common ancestor suffered a massive TEextinction, what remains a puzzle is the ability of the genometo remain TE free. Horizontal transfer of both LTRretrotransposons and DNA transposons is postulated to bea frequent occurrence and in fact it appears even necessary toexplain the persistence of these TEs over long evolutionarytime. It would seem that these unicellular organisms would beparticularly susceptible to horizontal transfer due to the lackof a protected germline. If these genomes are indeed TE free,

why and how they remain TE free is perplexing. Does their lifehistory as obligate intracellular parasites preclude theseorganisms from coming in contact with the vectors, like

viruses, that might act as intermediates for the horizontaltransfer of TEs? Have they developed a particularly effectiveline of defense against genomic invaders? Paradoxically,apicomplexans appear to have lost the RNA interferencemachinery, which has been shown to help protect against TEsandviruses in animalsand plants(Ullu et al. 2004). However, itis difficult to determineif this loss was secondary, asa result ofthe lack of threats posed by TEs or viruses or if the loss wascoincident with the loss of TEs. It is also worth mentioningthat Apicomplexans seem to have dearth of TEs despitehaving a sexual stage and going through meiosis.

Seven of the 8 species in the list inhabit the cell ofanother organism and their existence depends on exploita-tion of that organisms resources. The eighth organismCyanidioschyzon merolae is an extremophile, inhabiting anacidic hot-spring (Misumi et al. 2005). Intracellular parasites

might be expected to be under a strong selective constraintto maintain cell size in order to occupy the cellular niche,effectively. In addition, genome reduction is a generalfeature of intracellular pathogens. Most bacterial intracellu-lar pathogens, in concert with having a reduced genome arealso depauperate in TEs, with the notable exception of someRickettsiales species (Masui et al. 1999; Duron et al. 2005;Simser et al. 2005; Sanogo et al. 2007; Cordaux 2008). A keyto this puzzle may be that in addition, to providingresources, perhaps the intracellular host environment acts asa shield from exposure to the vectors that are necessary for

TE horizontal transfer, as mentioned above. Therefore, itmight be reasonable to expect that an intracellular pathogenmight initially lose its TEs through selection and drift, andthen maintain, a TE-free genome, as a side effect of theprotection from vectors, afforded by the inhabitation of theintracellular environment. Careful examination of thegenomes of unicellular eukaryotes will provide a betterpicture of the relative importance of different factors inexplaining the pattern seen.

Some Unicellular Eukaryotic Genomes are

Populated by TEs

Multiple phylogeneticallydiverse extracellularpathogens havehad their genomes sequenced and display a variety of TEsthathave accumulated with varied levels of success. For example,

TEs have been identified in the genomes ofLeishmania major,Trypanosoma brucei, T. cruzi (Kinetoplastids), Trichomonasvaginalis(Trichomonad), Giardia lamblia(Diplomonad) (Figure2B), Entamoeba dispar, E. histolytica, E. invadens, E. moshkovskii,and E. terrapinae (Archamoebae; Figure 2D) and Perkinsusmarinus (Alveolate; Figure 2E) (unpublished data). Most ofthese organisms are parasites and all display genomes ,200Mb in size. Taking a closer look at unicellular eukaryoticgenomes and in particular very small ones with seeminglyatypical life history traits (e.g., absence of sex, obligateintracellular parasites,. . .), may be an excellent means tobeganto decipher the relative importance of molecular, genetic,

environmental, and population level forces in defining TEcomposition and success.

Conclusions

Recent advances in genome sequencing have led to a vastaccumulation of TE data and allowed many interestingobservations to be made. For example, a remarkablediversity of TEs has been uncovered, some with strikingrelationships to viruses, revealing a dynamic relationshipbetween TEs and viruses. Consideration of the genomesequencing projects in a phylogenetic context reveals thatdespite the hundreds of eukaryotic genomes that have beensequenced, a strong bias in sampling exists. There isa general under-representation of unicellular eukaryotes anda dearth of genome projects in many branches of theeukaryotic phylogeny especially, in the supergroup, Rhizaria.

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This bias in sampling warrants an embargo on general-izations concerning the distribution and behavior of TEs ineukaryotes. Indeed, 9 eukaryotic genomes are apparentlydevoid of TEs altogether, upending the long held idea that

TEs are ubiquitous in eukaryotic taxa.The population biology of the genome is reminiscent of

an ecosystem where TEs are born, replicate and die and newpopulations emerge, migrate, and colonize other locationsas well as become extinct. This metaphor is not entirelyartificial as chromosomes and even regions of chromosomescan be compared with different ecological niches to which

TEs are more or less well adapted. Migration of TEs canoccur between chromosomes, as well as between individ-uals. In addition, there is competition between TEs forgenomic resources (host factors) as well as transpositionproteins, because the latter are generally encoded bya relatively small fraction of TEs within a given genome.

The factors that govern the TE diversity and richness ofa genome are complex and are likely to be a combination ofproperties intrinsic to the TE itself as well as extrinsic to thehost. Natural selection is acting on those TEs that are themost fit, where fitness is a measure of the number of copiesproduced without adversely affecting the fitness of the hostand/or the ability to colonize new environments. Un-derstanding the role of these factors in influencing thediversity and differential success of TE in genomes mayallow observed patterns in extant genomes to providea window into the past demographic history of the speciesin question. Small unicellular eukaryotic genomes are anexcellent substrate to study the role of various factors inpromoting TE diversity and composition.

Funding

National Institute of Health, National Institute of Allergy,and Infectious Disease (NIH 5R01AI068908-02).

Acknowledgments

I thank Michael Lynch for the invitation to participate in the 2007 American

Genetics Association Symposium: Mechanisms of Genome Evolution, and

Cedric Feschotte for critical review and comments on the manuscript.

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