The dynamics of transposable elements in structured populations

We analyzed the dynamics of transposable elements (TEs) according to Wright's island and continent-island models, assuming that selection tends to counter the deleterious effects of TEs. We showed that migration between host populations has no impact on either the existence or the stability of the TE copy number equilibrium points obtained in the absence of migration. However, if the migration rate is slower than the transposition rate or if selection is weak, then the TE copy numbers in all the populations can be expected to slowly become homogeneous, whereas a heterogeneous TE copy number distribution between populations is maintained if TEs are mobilized in some populations. The mean TE copy number is highly sensitive to the population size, but as a result of migration between populations, it decreases as the sum of the population sizes increases and tends to reach the same value in these populations. We have demonstrated the existence of repulsion between TE insertion sites, which is established by selection and amplified by drift. This repulsion is reduced as much as the migration rate is higher than the recombination rate between the TE insertion sites. Migration and demographic history are therefore strong forces in determining the dynamics of TEs within the genomes and the populations of a species.     

An Age-of-Allele Test of Neutrality for Transposable Element Insertions

How natural selection acts to limit the proliferation of transposable elements (TEs) in genomes has been of interest to evolutionary biologists for many years. To describe TE dynamics in populations, previous studies have used models of transposition–selection equilibrium that assume a constant rate of transposition. However, since TE invasions are known to happen in bursts through time, this assumption may not be reasonable. Here we propose a test of neutrality for TE insertions that does not rely on the assumption of a constant transposition rate. We consider the case of TE insertions that have been ascertained from a single haploid reference genome sequence. By conditioning on the age of an individual TE insertion allele (inferred by the number of unique substitutions that have occurred within the particular TE sequence since insertion), we determine the probability distribution of the insertion allele frequency in a population sample under neutrality. Taking models of varying population size into account, we then evaluate predictions of our model against allele frequency data from 190 retrotransposon insertions sampled from North American and African populations of Drosophila melanogaster. Using this nonequilibrium neutral model, we are able to explain ∼80% of the variance in TE insertion allele frequencies based on age alone. Controlling for both nonequilibrium dynamics of transposition and host demography, we provide evidence for negative selection acting against most TEs as well as for positive selection acting on a small subset of TEs. Our work establishes a new framework for the analysis of the evolutionary forces governing large insertion mutations like TEs, gene duplications, or other copy number variants.     

The fate of transposable elements in asexual populations

Sexual reproduction and recombination are important for maintaining a stable copy number of transposable elements (TEs). In sexual populations, elements can be contained by purifying selection against host carriers with higher element copy numbers; however, in the absence of sex and recombination, asexual populations could be driven to extinction by an unchecked proliferation of TEs. Here we provide a theoretical framework for analyzing TE dynamics under asexual reproduction. Analytic results show that, in an infinite asexual population, an equilibrium in copy number is achieved if no element excision is possible, but that all TEs are eliminated if there is some excision. In a finite population, computer simulations demonstrate that small populations are driven to extinction by a Muller's ratchet-like process of element accumulation, but that large populations can be cured of vertically transmitted TEs, even with excision rates well below transposition rates. These results may have important consequences for newly arisen asexual lineages and may account for the lack of deleterious retrotransposons in the putatively ancient asexual bdelloid rotifers.     

Sure facts, speculations, and open questions about the evolution of transposable element copy number

Transposable elements (TEs) are sequences capable of multiplying in their host's genome. They survive by increasing copy numbers due to transpositions, and natural selection washes them out because hosts with heavier loads of TEs have lower fitness. The available phylogenetic evidence supports the view that TEs have existed in living organisms for hundreds of millions of years. A fundamental question facing the field is how can an equilibrium be attained between transposition and selection which allows these parasitic genetic elements to persist for such a long time period? To answer this question, it is necessary to understand how the rate of TE transposition is controlled and to describe the mechanisms with which natural selection opposes TE accumulation. Perhaps the best models for such a study are copia and gypsy retrotransposons in Drosophila. Their average rate of transposition in nature is between 10^?5 ? 10^?4 transpositions per copy per generation. Unlike nature, transposition rates vary widely, from zero to 10^?2, between laboratory lines. This variability in transposition rate is controlled by host genes. It is probable that in nature TE site heterogeneity is caused by frequent transpositions in rare flies with permissive alleles, and no transpositions happen in the rest of flies. The average rate of TE transposition in nature may thus depend on the frequency of permissive alleles, which is a function of the rate of mutation from restrictive to permissive alleles, the mechanism and the strength of selection opposing TE multiplication, and population size. Thus, evolution of the frequency of permissive alleles of genes controlling transposition must be accounted for to understand evolution of TE copy numbers.     

Transposable Element Numbers in Cosmopolitan Inversions from a Natural Population of Drosophila Melanogaster

Population studies of the distribution of transposable elements (TEs) on the chromosomes of Drosophila melanogaster have suggested that their copy number increase due to transposition is balanced by some form of natural selection. Theory suggests that, as a consequence of deleterious ectopic meiotic exchange between TEs, selection can favor genomes with lower TE copy numbers. This predicts that TEs should be less deleterious, and hence more abundant, in chromosomal regions in which recombination is reduced. To test this, we surveyed the abundance and locations of 10 families of TEs in recombination-suppressing chromosomal inversions from a natural population. The sample of 49 chromosomes included multiple independent isolates of seven different inversions and a corresponding set of standard chromosomes. For all 10 TE families pooled, copy numbers were significantly higher overall within low frequency inversions than within corresponding regions of standard chromosomes. TEs occupied chromosomal sites at significantly higher frequencies within the In(3R)M0 and In(3R)K inversions than within the corresponding regions of standard 3R chromosomes. These results are consistent with the predictions of the ectopic exchange model.     

Potential Role of Transposable Elements in the Rapid Reorganization of the Fusarium oxysporum Genome

The activity of several families of transposable elements (TEs) in the genome of Fusarium oxysporum represents a potential source of karyotypic instability. We investigated transposon-mediated chromosome rearrangements by analyzing the karyotypes of a set of strains in which transposition events had occurred. We uncovered exceptional electrophoretic karyotype (EK) variability, in both number and size of chromosomal bands. We showed that EK differences result from chromosomal translocations, large deletions, and even more complex rearrangements. We also revealed many duplicated chromosomal regions. By following transposition of two elements and analyzing the distribution of different families of TEs on whole chromosomes, we find (i) no evidence of chromosomal breakages induced by transposition, (ii) a clustering of TEs in some regions, and (iii) a correlation between the high level of chromosomal polymorphism and the concentration of TEs. These results suggest that chromosome length polymorphisms likely result from ectopic recombination between TEs that can serve as substrates for these changes.     

Synergistic epistasis of the deleterious effects of transposable elements

The replicative nature and generally deleterious effects of transposable elements (TEs) raise an outstanding question about how TE copy number is stably contained in host populations. Classic theoretical analyses predict that, when the decline in fitness due to each additional TE insertion is greater than linear, or when there is synergistic epistasis, selection against TEs can result in a stable equilibrium of TE copy number. While several mechanisms are predicted to yield synergistic deleterious effects of TEs, we lack empirical investigations of the presence of such epistatic interactions. Purifying selection with synergistic epistasis generates repulsion linkage between deleterious alleles. We investigated this population genetic signal in the likely ancestral Drosophila melanogaster population and found evidence supporting the presence of synergistic epistasis among TE insertions, especially TEs expected to exert large fitness impacts. Even though synergistic epistasis of TEs has been predicted to arise through ectopic recombination and TE-mediated epigenetic silencing mechanisms, we only found mixed support for the associated predictions. We observed signals of synergistic epistasis for a large number of TE families, which is consistent with the expectation that such epistatic interaction mainly happens among copies of the same family. Curiously, significant repulsion linkage was also found among TE insertions from different families, suggesting the possibility that synergism of TEs’ deleterious fitness effects could arise above the family level and through mechanisms similar to those of simple mutations. Our findings set the stage for investigating the prevalence and importance of epistatic interactions in the evolutionary dynamics of TEs.     

Three Groups of Transposable Elements with Contrasting Copy Number Dynamics and Host Responses in the Maize (Zea mays ssp. mays) Genome

Most angiosperm nuclear DNA is repetitive and derived from silenced transposable elements (TEs). TE silencing requires substantial resources from the plant host, including the production of small interfering RNAs (siRNAs). Thus, the interaction between TEs and siRNAs is a critical aspect of both the function and the evolution of plant genomes. Yet the co-evolutionary dynamics between these two entities remain poorly characterized. Here we studied the organization of TEs within the maize (Zea mays ssp mays) genome, documenting that TEs fall within three groups based on the class and copy numbers. These groups included DNA elements, low copy RNA elements and higher copy RNA elements. The three groups varied statistically in characteristics that included length, location, age, siRNA expression and 24∶22 nucleotide (nt) siRNA targeting ratios. In addition, the low copy retroelements encompassed a set of TEs that had previously been shown to decrease expression within a 24 nt siRNA biogenesis mutant (mop1). To investigate the evolutionary dynamics of the three groups, we estimated their abundance in two landraces, one with a genome similar in size to that of the maize reference and the other with a 30% larger genome. For all three accessions, we assessed TE abundance as well as 22 nt and 24 nt siRNA content within leaves. The high copy number retroelements are under targeted similarly by siRNAs among accessions, appear to be born of a rapid bust of activity, and may be currently transpositionally dead or limited. In contrast, the lower copy number group of retrolements are targeted more dynamically and have had a long and ongoing history of transposition in the maize genome.     

Size matters: non-LTR retrotransposable elements and ectopic recombination in Drosophila

The Drosophila melanogaster genome contains approximately 100 distinct families of transposable elements (TEs). In the euchromatic part of the genome, each family is present in a small number of copies (5-150 copies), with individual copies of TEs often present at very low frequencies in populations. This pattern is likely to reflect a balance between the inflow of TEs by transposition and the removal of TEs by natural selection. The nature of natural selection acting against TEs remains controversial. We provide evidence that selection against chromosome abnormalities caused by ectopic recombination limits the spread of some TEs. We also demonstrate for the first time that some TE families in the Drosophila euchromatin appear to be only marginally affected by purifying selection and contain many copies at high population frequencies. We argue that TEs in these families attain high population frequencies and even reach fixation as a result of low family-wide transposition rates leading to low TE copy numbers and consequently reduced strength of selection acting on individual TE copies. Fixation of TEs in these families should provide an upward pressure on the size of intergenic sequences counterbalancing rapid DNA loss through small deletions. Copy-number-dependent selection on TE families caused by ectopic recombination may also promote diversity among TEs in the Drosophila genome.     

Intracellular battlegrounds: conflict and cooperation between transposable elements

Transposable elements (TEs) are genomic parasites that amplify their own representation on hosts' chromosomes by inserting into new positions. It is traditionally thought that their copy number is regulated by purifying selection that eliminates hosts with higher than average TE abundance. Here, we stress that selection due to beneficial or harmful interactions between TEs introduces a whole new dimension, with implications for TE evolutionary trajectories and TE loads on hosts. This framework poses new questions requiring conceptual and experimental advances. Considering primarily Drosophila data, we make a case for within host selection on TEs by thinking expansively about the lifecycle of several TE families.     

Conserved fragments of transposable elements in intergenic regions: evidence for widespread recruitment of MIR- and L2-derived sequences within the mouse and human genomes

We analysed the distribution of transposable elements (TEs) in 100 aligned pairs of orthologous intergenic regions from the mouse and human genomes. Within these regions, conserved segments of high similarity between the two species alternate with segments of low similarity. Identifiable TEs comprise 40-60% of segments of low similarity. Within such segments, a particular copy of a TE found in one species has no orthologue in the other. Overall, TEs comprise only approximately 20 % of conserved segments. However, TEs from two families, MIR and L2, are rather common within conserved segments. Statistical analysis of the distributions of TEs suggests that a majority of the MIR and L2 elements present in murine intergenic regions have human orthologues. These elements must have been present in the common ancestor of human and mouse and have remained under substantial negative selection that prevented their divergence beyond recognition. If so, recruitment of MIR- and L2-derived sequences to perform a function that increases host fitness is rather common, with at least two such events per host gene. The central part of the MIR consensus sequence is over-represented in conserved segments given its background frequency in the genome, suggesting that it is under the strongest selective constraint.     

Fitness costs of Doc expression are insufficient to stabilize its copy number in Drosophila melanogaster

The stable coexistence of transposable elements (TEs) with their host genome over long periods of time suggests TEs have to impose some deleterious effect upon their host fitness. Three mechanisms have been proposed to account for the deleterious effect caused by TEs: host gene interruptions by TE insertions, chromosomal rearrangements by TE-induced ectopic recombination, and costly TE expression. However, the relative importance of these mechanisms remains controversial. Here, we test specifically if TE expression accounts for the host fitness cost imposed by TE insertions. In the retrotransposon Doc, expression requires binding of the host RNA polymerase to the internal promoter. If expression of Doc elements is deleterious to their host, Doc copies with promoters would be more strongly selected against and would persist in the population for shorter periods of time compared with Docs lacking promoters. We tested this prediction using sequence-specific amplified polymorphism (SSAP) analyses. We compared the populations of these two types of Doc elements in two sets of lines of Drosophila melanogaster: selection-free isogenic lines accumulating new Doc insertions and isogenized isofemale lines sampled from a natural population. We found that (1) there is no difference in the proportion of promoter-bearing and promoter-lacking copies between sets of lines, and (2) the site occupancy distribution of promoter-bearing copies does not skew toward lower frequency compared with that of promoter-lacking copies. Thus, selection against promoter-bearing copies does not appear to be stronger than that of promoter-lacking copies. Our results show that expression is not playing a major role in stabilizing Doc copy numbers.     

New regulatory regions of Drosophila 412 retrotransposable element generated by recombination

There are no doubts that transposable elements (TEs) have greatly influenced genomes evolution. They have, however, evolved in different ways throughout mammals, plants, and invertebrates. In mammals they have been shown to be widely present but with low transposition activity; in plants they are responsible for large increases in genome size. In Drosophila, despite their low amount, transposition seems to be higher. Therefore, to understand how these elements have evolved in different genomes and how host genomes have proposed to go around them, are major questions on genome evolution. We analyzed sequences of the retrotransposable elements 412 in natural populations of the Drosophila simulans and D. melanogaster species that greatly differ in their amount of TEs. We identified new subfamilies of this element that were the result of mutation or insertion-deletion process, but also of interfamily recombinations. These new elements were well conserved in the D. simulans natural populations. The new regulatory regions produced by recombination could give rise to new elements able to overcome host control of transposition and, thus, become potential genome invaders.     

The control of copy number of IS6110 in Mycobacterium tuberculosis

Insertion sequence (IS) elements are bacterial genes that are able to transpose to different locations in the genome. These elements are often used in molecular epidemiology as genetic markers that track the spread of pathogens. Transposable elements have frequently been described as "selfish DNA" because they facilitate their own transposition, causing damage when they insert into coding regions, while contributing little if anything to the bacterial host. According to this hypothesis, the expansion of copy number of insertion sequences is opposed by negative selection against high copy numbers. From an alternative point of view, we might expect IS elements to intrinsically regulate transposition within cells, thereby limiting damage to their bacterial host. Here, we report evidence that the copy number of IS6110 in Mycobacterium tuberculosis is controlled by selection against the element. We first construct 12 different models of marker change resulting from a combination of possible transposition functions and selective regimes. We then compute the Akaike Information Criterion for each model to identify the models that best explain data consisting of serial isolates of M. tuberculosis genotyped with IS6110. We find that the best performing models all include selection against the accumulation of copies. Specifically, our analysis points to the interaction of separate copies of the element causing lethal effects. We discuss the implications of these findings for genome evolution and molecular epidemiology.     

Effects of recombination rate on human endogenous retrovirus fixation and persistence

Endogenous retroviruses (ERVs) result from germ line infections by exogenous retroviruses. They can proliferate within the genome of their host species until they are either inactivated by mutation or removed by recombinational deletion. ERVs belong to a diverse group of mobile genetic elements collectively termed transposable elements (TEs). Numerous studies have attempted to elucidate the factors determining the genomic distribution and persistence of TEs. Here we show that, within humans, gene density and not recombination rate correlates with fixation of endogenous retroviruses, whereas the local recombination rate determines their persistence in a full-length state. Recombination does not appear to influence fixation either via the ectopic exchange model or by indirect models based on the efficacy of selection. We propose a model linking rates of meiotic recombination to the probability of recombinational deletion to explain the effect of recombination rate on persistence. Chromosomes 19 and Y are exceptions, possessing more elements than other regions, and we suggest this is due to low gene density and elevated rates of human ERV integration in males for chromosome Y and segmental duplication for chromosome 19.     

Transposable elements in clonal lineages: lethal hangover from sex

Long-term coevolution of transposable elements (TEs) in sexual hosts leads to evolution of extremely active and dangerous mutagens kept in tenuous check by host-derived mechanisms and via natural selection against TE-rich genomes. To the extent that sexual reproduction and recombination are important in maintaining a stable TE copy number and a tolerable mutation load, the switch to clonality from sexual reproduction can be extremely damaging and, generally, should lead to clonal lineage extinction. Surprisingly however, the loss of powerful selective mechanisms constraining TEs can be beneficial in the short-term by immediately eliminating selective load and possibly promoting the early success of clonal lineages. The clonal lineages that do survive in the long-term must find a way to eliminate or domesticate TEs. Indeed bdelloid rotifers, which are ancient asexuals, do appear to have lost most of the otherwise wide-spread TEs and might have domesticated others. The path to this TE-free haven is anything but clear at the moment. We have considered a novel scenario of instantaneous inactivation of TEs by starting off with a genome carrying repressive host alleles for all TEs in the genome. We show that such a scenario appears plausible and provide some limited empirical evidence in its support.  © 2003 The Linnean Society of London, Biological Journal of the Linnean Society , 2003, 79 , 33–41.     

Patterns of insertion and deletion in contrasting chromatin domains

Transposable elements (TEs) play a fundamental role in the evolution of genomes. In Drosophila they are disproportionately represented in regions of low recombination, such as in heterochromatin. This pattern has been attributed to selection against repeated elements in regions of normal recombination, owing to either (1) the slightly deleterious position effects of TE insertions near or into genes, or (2) strong selection against chromosomal abnormalities arising from ectopic exchange between TE repeats. We have used defective non-long-terminal repeat (LTR) TEs that are "dead-on-arrival" (DOA) and unable to transpose in order to estimate spontaneous deletion rates in different constituents of chromatin. These elements have previously provided evidence for an extremely high rate of spontaneous deletion in Drosophila as compared with mammals, potentially explaining at least part of the differences in the genome sizes in these organisms. However, rates of deletion could be overestimated due to positive selection for a smaller likelihood of ectopic exchange. In this article, we show that rates of spontaneous deletion in DOA repeats are as high in heterochromatin and regions of euchromatin with low recombination as they are in regions of euchromatin with normal recombination. We have also examined the age distribution of five non-LTR families throughout the genome. We show that there is substantial variation in the historical pattern of transposition of these TEs. The overrepresentation of TEs in the heterochromatin is primarily due to their longer retention time in heterochromatin, as evidenced by the average time since insertion. Fragments inserted recently are much more evenly distributed in the genome. This contrast demonstrates that the accumulation of TEs in heterochromatin and in euchromatic regions of low recombination is not due to biased transposition but by greater probabilities of fixation in these regions relative to regions of normal recombination.     

It takes two transposons to tango: transposable-element-mediated chromosomal rearrangements

Transposable elements (TEs) promote various chromosomal rearrangements more efficiently, and often more specifically, than other cellular processes(1-3). One explanation of such events is homologous recombination between multiple copies of a TE present in a genome. Although this does occur, strong evidence from a number of TE systems in bacteria, plants and animals suggests that another mechanism - alternative transposition - induces a large proportion of TE-associated chromosomal rearrangements. This paper reviews evidence for alternative transposition from a number of unrelated but structurally similar TEs. The similarities between alternative transposition and V(D)J recombination are also discussed, as is the use of alternative transposition as a genetic tool.     

Transposons but not retrotransposons are located preferentially in regions of high recombination rate in Caenorhabditis elegans

We analyzed the distribution of transposable elements (TEs: transposons, LTR retrotransposons, and non-LTR retrotransposons) in the chromosomes of the nematode Caenorhabditis elegans. The density of transposons (DNA-based elements) along the chromosomes was found to be positively correlated with recombination rate, but this relationship was not observed for LTR or non-LTR retrotransposons (RNA-based elements). Gene (coding region) density is higher in regions of low recombination rate. However, the lower TE density in these regions is not due to the counterselection of TE insertions within exons since the same positive correlation between TE density and recombination rate was found in noncoding regions (both in introns and intergenic DNA). These data are not compatible with a global model of selection acting against TE insertions, for which an accumulation of elements in regions of reduced recombination is expected. We also found no evidence for a stronger selection against TE insertions on the X chromosome compared to the autosomes. The difference in distribution of the DNA and RNA-based elements along the chromosomes in relation to recombination rate can be explained by differences in the transposition processes.     

Genomic parasites or symbionts? Modeling the effects of environmental pressure on transposition activity in asexual populations

Transposable elements are DNA segments capable of persisting in host genomes by self-replication in spite of deleterious mutagenic effects. The theoretical dynamics of these elements within genomes has been studied extensively, and population genetic models predict that they can invade and maintain as a result of both intra-genomic and inter-individual selection in sexual species. In asexuals, the success of selfish DNA is more difficult to explain. However, most theoretical work assumes constant environment. Here, we analyze the impact of environmental change on the dynamics of transposition activity when horizontal DNA exchange is absent, based on a stochastic computational model of transposable element proliferation. We argue that repeated changes in the phenotypic optimum in a multidimensional fitness landscape may induce explosive bursts of transposition activity associated with faster adaptation. However, long-term maintenance of transposition activity is unlikely. This could contribute to the significant variation in the transposable element copy number among closely related species.