The impact of transposable elements on eukaryotic genomes: From genome size increase to genetic adaptation to stressful environments

Transposable elements (TEs) are present in roughly all genomes. These mobile DNA sequences are able to invade genomes and their impact on genome evolution is substantial. The mobility of TEs can induce the appearance of deleterious mutations, gene disruption and chromosome rearrangements, but transposition activity also has positive aspects and the mutational activities of TEs contribute to the genetic diversity of organisms. This short review aims to give a brief overview of the impact TEs may have on animal and plant genome structure and expression, and the relationship between TEs and the stress response of organisms, including insecticide resistance.     

Population genetics models of competition between transposable element subfamilies

Transposable elements are one of the major components of genomes. Some copies are fully efficient; i.e., they are able to produce the proteins needed for their own transposition, and they can move and duplicate into the genome. Other copies are mutated. They may have lost their moving ability, their coding capacity, or both, thus becoming pseudogenes slowly eliminated from the genome through deletions and natural selection. Little is known about the dynamics of such mutant elements, particularly concerning their interactions with autonomous copies. To get a better understanding of the transposable elements' evolution after their initial invasion, we have designed a population genetics model of transposable elements dynamics including mutants or nonfunctional sequences. We have particularly focused on the case where these sequences are nonautonomous elements, known to be able to use the transposition machinery produced by the autonomous ones. The results show that such copies generally prevent the system from achieving a stable transposition-selection equilibrium and that nonautonomous elements can invade the system at the expense of autonomous ones. The resulting dynamics are mainly cyclic, which highlights the similarities existing between genomic selfish DNA sequences and host-parasite systems.     

Mobile dispersed genetic elements in eukaryotes and their possible relationship to carcinogenesis

During last three years, the mobile dispersed genetic elements (mdg) were isolated from the genome of Drosophila melanogaster, yeasts and mammals. According to a number of their properties, mdg elements are quite similar to endogenous pro-retroviruses. It is known that in many cases oncogeneity of retroviruses depends on the incorporation of the certain host genes (potential oncogenes) into the viral genome. We suggest that in some cases mdg elements could entrap the potential oncogenes in the course of transposition. As a result, oncogenes become uncontrollable by host regulatory systems and may induce cell transformation. Another possible mechanism underlying switch off of the gene responsible for differentiation control may be mdg transposition to a region in close vicinity of the gene. As transposition of mdg elements seems to occur rather often, they may be regarded as one of the most important factors of genome rearrangements leading to cell transformation.     

Genomic factors regulating the transposition of drosophila mobile elements

Data on regulation and genetic control of transposition of mobile genetic elements (ME) in Drosophila are reviewed with special emphasis on the most abundant and best studied class of ME, retrotransposons. The effects of cis- and trans-acting factors on their expression are analyzed. Loci of the host genome involved in regulating their transposition are considered.     

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.     

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.     

Symbiotic DNA in eukaryotic genomes

The recent explosive growth of molecular genetic databases has yielded increasingly detailed insights into the evolutionary dynamics of eukaryotic genomes. DNA sequences with the self-encoded ability to transpose and replicate are unexpectedly abundant and widespread in eukaryotic genomes. They seem to be sexual parasites. By dispersing themselves among the chromosomes, they increase their transmission rates and can invade outcrossing populations despite reducing host fitness. Once established, molecular parasites may themselves be parasitized by other elements, and through selection for reduced virulence may become beneficial genes. Elements have been isolated at various stages in this progression, from transposons that regulate their own transposition rates, to fundamental components of eukaryotic cytology, such as telomeres.     

植物中的反转录转座子及其应用

反转录转座子是植物中最不稳定的遗传元件之一,它们对基因组的大小、结构、功能和进化都有重要作用。本文综述了近年来对植物反转录转座子类型和结构、在基因组中表达、调控、转座活动、进化等方面的研究进展,讨论了它们在遗传研究中的应用前景。 Abstract:Retrotransposons are one of the most unstable genetic elements in the plant kingdom,they have the potential to dramatically affect gene function and host genome structure.The current status of their types and structure,expression regulation,transposition,and evolution are reviewed.Their potential as genetic tools are also discussed.     

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.     

A branching process for the early spread of a transposable element in a diploid population

Transposable elements (TEs) face significant challenges upon transfer into a new host population, invariably beginning their invasion with only a single element. The fate of this element is a product of its internal properties, the population dynamics of the host species, and genetic drift. We present a continuous-time multi-type branching process to model the early stages of TE spread. The model incorporates seasonal population size changes and is applicable to diploid hosts for prevalences up to 10%. We reproduce standard results of TE population dynamics and show that population growth may have a greater influence on reducing TE loss probability than a transpositional burst. These results are applied to the planned use of a TE to drive an antimalarial gene into an Anopheles gambiae population. The model favors a transgenic release immediately following the dry season when the An. gambiae population begins to grow. Increasing the number of transgenic hosts released has the greatest influence on reducing the probability of TE loss. Following release, the rate at which the TE increases its proportion in the population is most sensitive to its replicative transposition rate. The model recommends a replicative transposition rate greater than 0.1 per TE per generation to satisfy public health goals.     

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.     

piRNA抑制基因转座的分子机制

转座子是一类可以在染色体上或不同染色体间自由移动的DNA。在高等生物中,处于活跃状态的转座子多为通过RNA中间体进行转座的逆转录转座子。由于逆转录转座子在细胞基因组中占有很高的比例,它的频繁转座能引起细胞基因组结构和功能的改变,导致癌症等严重基因疾病的发生,因此宿主细胞在长期的进化中形成了多种自我保护机制用以控制逆转录转座子活性。属于非编码小RNA的piRNA以其独特的机制在转录及转录后水平控制逆转录转座子RNA中间体的产生,抑制了逆转录转座过程的发生。本文总结了近年来piRNA控制转座子转座相关分子机制的研究进展,以期为转座子及基因调控方面的研究工作提供一些参考。     

A branching-process model for the evolution of transposable elements incorporating selection

We have formulated a very general mathematical model to analyze the evolution of transposable genetic elements in prokaryotic populations. Transposable genetic elements are DNA sequences able to replicate and insert copies of themselves at new locations in the genome. This work characterizes the equilibrium distribution of copy number under the influence of copy number-dependent selection, transposition and deletion. Our principal results concern the equilibrium distribution of copy number in response to various selective regimes. For particular transposition patterns (e.g. unregulated transposition or copy number-dependent transposition), equilibrium distributions are calculated numerically for a variety of specific selection patterns. Selection is quantified through specification of the expected number of offspring for individuals of each type, which is generally a non-increasing function of copy number, in accord with the usual evolutionary speculations.     

Mobile DNA can drive lineage extinction in prokaryotic populations

Natural selection ultimately acts on genes and other DNA sequences. Adaptations that are good for the gene can have adverse effects at higher levels of organization, including the individual or the population. Mobile genetic elements illustrate this principle well, because they can self‐replicate within a genome at a cost to their host. As they are costly and can be transmitted horizontally, mobile elements can be seen as genomic parasites. It has been suggested that mobile elements may cause the extinction of their host populations. In organisms with very large populations, such as most bacteria, individual selection is highly effective in purging genomes of deleterious elements, suggesting that extinction is unlikely. Here we investigate the conditions under which mobile DNA can drive bacterial lineages to extinction. We use a range of epidemiological and ecological models to show that harmful mobile DNA can invade, and drive populations to extinction, provided their transmission rate is high and that mobile element‐induced mortality is not too high. Population extinction becomes more likely when there are more elements in the population. Even if elements are costly, extinction can still occur because of the combined effect of horizontal gene transfer, a mortality induced by mobile elements. Our study highlights the potential of mobile DNA to be selected at the population level, as well as at the individual level.     

The interaction between mobile DNAs and their hosts in a fluctuating environment

The interaction between mobile DNA sequences and their hosts raises important questions in the context of hosts which reproduce clonally with only rare horizontal transmission between clones. The activity of some mobile DNAs as reversible mutators of genes raises the possibility that, in a fluctuating environment, cells may gain an advantage if they have mobile DNAs which mutate genes whose inactivation is favoured in one of the environments that the population encounters. Here we analyse a model of this process and ask what would be the optimal rate of transposition in a population whose elements are maintained by this mechanism. We also examine the impact of horizontal transfer on such a population. With movement of elements between cells, we can imagine elements with differing rates of transposition and host cells with differing rates of transposition. We find that evolution in the population of elements favours a rapid rate of transposition, and evolution of the host cells favours cells in which this rapid rate of element-dependent transposition results in an optimal rate of transposition per cell. However, when horizontal transfer rates are high, some unexpected features of the model are observed. In particular, a polymorphism between cell types (some with an optimal rate of transposition and some with no transposition at all from endogenous elements) can be stably maintained. We consider the possible biological predictions of this analysis.     

Evolutionary forces generating sequence homogeneity and heterogeneity within retrotransposon families

Genome projects allow us to sample copies of a retrotransposon sequence family residing in a host genome. The variation in DNA sequence between these individual copies will reflect the evolutionary process that has spread the sequences through the genome. Here I review quantitatively the expected diversity of elements belonging to a transposable genetic element family. I use a simple neutral model for replicative mobile DNAs such as retrotransposons to predict the extent of sequence variability between members of a single family of transposable elements, both within and between species. The effects of horizontal transfer are also explored. I also consider the impact on these distributions of an increase in transposition rate arising from a mutational change in copy of the sequence. In addition, I consider the question of the interaction between retrotransposons and their hosts, and the causes of the abundance of transposable elements in the genomes that they occupy.     

Applications of retrotransposons as genetic tools in plant biology

Retrotransposons are mobile genetic elements that accomplish transposition via an RNA intermediate that is reverse transcribed before integration into a new location within the host genome. They are ubiquitous in eukaryotic organisms and constitute a major portion of the nuclear genome (often more than half of the total DNA) in plants. Furthermore, they are dispersed as interspersed repetitive sequences throughout most of the length of all host chromosomes. These unique properties of retrotransposons have been exploited as genetic tools for plant genome analysis. Major applications are in determining phylogeny and genetic diversity and in the functional analyses of genes in plants. Here, recent advances in molecular markers, gene tagging and functional genomics technologies using plant retrotransposons are described.     

Segregational Drift Constrains the Evolutionary Rate of Prokaryotic Plasmids

Plasmids are extrachromosomal genetic elements in prokaryotes that have been recognized as important drivers of microbial ecology and evolution. Plasmids are found in multiple copies inside their host cell where independent emergence of mutations may lead to intracellular genetic heterogeneity. The intracellular plasmid diversity is thus subject to changes upon cell division. However, the effect of plasmid segregation on plasmid evolution remains understudied. Here, we show that genetic drift during cell division—segregational drift—leads to the rapid extinction of novel plasmid alleles. We established a novel experimental approach to control plasmid allele frequency at the levels of a single cell and the whole population. Following the dynamics of plasmid alleles in an evolution experiment, we find that the mode of plasmid inheritance—random or clustered—is an important determinant of plasmid allele dynamics. Phylogenetic reconstruction of our model plasmid in clinical isolates furthermore reveals a slow evolutionary rate of plasmid-encoded genes in comparison to chromosomal genes. Our study provides empirical evidence that genetic drift in plasmid evolution occurs at multiple levels: the host cell and the population of hosts. Segregational drift has implications for the evolutionary rate heterogeneity of extrachromosomal genetic elements.