Transposable elements as artisans of the heterochromatic genome in Drosophila melanogaster

Over 50 years ago Barbara McClintock discovered that maize contains mobile genetic elements, but her findings were at first considered nothing more than anomalies. Today it is widely recognized that transposable elements have colonized all eukaryotic genomes and represent a major force driving evolution of organisms. Our contribution to this special issue deals with the theme of transposable element-host genome interactions. We bring together published and unpublished work to provide a picture of the contribution of transposable elements to the evolution of the heterochromatic genome in Drosophila melanogaster. In particular, we discuss data on 1) colonization of constitutive heterochromatin by transposable elements, 2) instability of constitutive heterochromatin induced by the I factor, and 3) evolution of constitutive heterochromatin and heterochromatic genes driven by transposable elements. Drawing attention to these topics may have direct implications on important aspects of genome organization and gene expression.     

The evolution and suppression of male suicide under paternal genome elimination

Different genetic systems can be both the cause and the consequence of genetic conflict over the transmission of genes, obscuring their evolutionary origin. For instance, with paternal genome elimination (PGE), found in some insects and mites, both sexes develop from fertilized eggs, but in males the paternally derived chromosomes are either lost (embryonic PGE) or deactivated (germline PGE) during embryogenesis and not transmitted to the next generation. Evolution of germline PGE requires two transitions: (1) elimination of the paternal genome during spermatogenesis; (2) deactivation of the paternal genome early in development. Hypotheses for the evolution of PGE have mainly focused on the first transition. However, maternal genes seem to be responsible for the deactivation and here we investigate if maternal suppression could have evolved in response to paternally expressed male suicide genes. We show that sibling competition can cause such genes to spread quickly and that inbreeding is necessary to prevent fixation of male suicide, and subsequent population extinction. Once male-suicide has evolved, maternally expressed suppressor genes can invade in the population. Our results highlight the rich opportunity for genetic conflict in asymmetric genetic systems and the counterintuitive phenotypes that can evolve as a result.     

Transposable elements, gene creation and genome rearrangement in flowering plants

Plant genome structure is largely derived from the differing specificities, abundances and activities of transposable elements. Recent studies indicate that both the amplification and the removal of transposons are rapid processes in plants, accounting for the general lack of intergenic homology between species that last shared a common ancestor more than 10 million years ago. Two newly discovered transposon varieties, Helitrons and Pack-MULEs, acquire and fuse fragments of plant genes, creating the raw material for the evolution of new genes and new genetic functions. Many of these recently assembled, chimeric gene-candidates are expressed, suggesting that some might escape epigenetic silencing and mutational decay, but a proven case of gene creation by any transposable element activity in plants remains to be demonstrated.     

Organization of the Escherichia coli genome

A review of literature data reveals that for the last years, the molecular biology techniques have been of an increasing use in the study of the Escherichia coli genome, having supplemented the standard genetic mapping. For the proper understanding of the Escherichia coli genome organization, recombinational events occurring in the course of evolution should be considered. The bacterial genome seems to carry traces of both "long-term" evolution, possibly responsible for appearance of the bacterial cell itself, and "current" evolution, consisting mainly of periodic genome entering by new plasmid-originated genes. It is supposed that in the process of stabilization within a genome, every new gene undergoes a stage of the "transgene", that is the gene situated in a transposon on the chromosome. In parallel with integration of new genes into the genome, some genes deleting should also take place. The formation of deletions could occur by unequal crossing over in segments of direct homologous repeats which seem to be ordinarily revealed in the experimental study of the tandem gene duplications.     

Impact of transposable elements on the evolution of mammalian gene regulation

Transposable elements (TEs) are present in all organisms and nearly half of the human and mouse genome is derived from ancient transpositions. This fact alone suggests that TEs have played a major role in genome organization and evolution. Studies undertaken over the last two decades or so clearly show that TEs of various kinds have played an important role in organism evolution. Here we review the impact TEs have on the evolution of gene regulation and gene function with an emphasis on humans. Understanding the mechanisms resulting in genomic change is central to our understanding of gene regulation, genetic disease and genome evolution. Full comprehension of these biological processes is not possible without an in depth knowledge of how TEs impact upon the genome.     

Cytoplasmic inheritance and intragenomic conflict

The differing inheritance patterns of cytoplasmic genes and the sex chromosomes from the Mendelian autosomal patterns can be used to divide the genome into fractions whose defining rule is that the fitness of all genes in a set is maximized in the same way. Each set will be selected to modify the phenotype of the organism in a way which maximally propagates the genes comprising the set, and hence in ways inconsistent with the other sets which comprise the total genome. The coexistence of such multiple sets in the same genome creates intragenomic conflict. Evidence is presented in which the fitness of cytoplasmic and other non-autosomal genetic sets are increased at the expense of the autosomal genetic set. The relationship of such intragenomic conflict to the evolution of anisogamy, dioecy, skewed sex ratios, differential male mortality, systems of sex determination, and altruism is discussed.     

Ancient adaptive evolution of the primate antiviral DNA-editing enzyme APOBEC3G

Host genomes have adopted several strategies to curb the proliferation of transposable elements and viruses. A recently discovered novel primate defense against retroviral infection involves a single-stranded DNA-editing enzyme, APOBEC3G, that causes hypermutation of HIV. The HIV-encoded virion infectivity factor (Vif) protein targets APOBEC3G for destruction, setting up a genetic conflict between the APOBEC3G and Vif genes. This kind of conflict leads to rapid fixation of mutations that alter amino acids at the protein–protein interface, referred to as positive selection. We show that the APOBEC3G gene has been subject to strong positive selection throughout the history of primate evolution. Unexpectedly, this selection appears more ancient than, and is likely only partially caused by, modern lentiviruses. Furthermore, five additional APOBEC genes in the human genome appear to be engaged in similar genetic conflicts, displaying some of the highest signals for positive selection in the human genome. Despite being only recently discovered, editing of RNA and DNA may thus represent an ancient form of host defense in primate genomes.     

Evolution of genome architecture

Charles Darwin believed that all traits of organisms have been honed to near perfection by natural selection. The empirical basis underlying Darwin's conclusions consisted of numerous observations made by him and other naturalists on the exquisite adaptations of animals and plants to their natural habitats and on the impressive results of artificial selection. Darwin fully appreciated the importance of heredity but was unaware of the nature and, in fact, the very existence of genomes. A century and a half after the publication of the "Origin", we have the opportunity to draw conclusions from the comparisons of hundreds of genome sequences from all walks of life. These comparisons suggest that the dominant mode of genome evolution is quite different from that of the phenotypic evolution. The genomes of vertebrates, those purported paragons of biological perfection, turned out to be veritable junkyards of selfish genetic elements where only a small fraction of the genetic material is dedicated to encoding biologically relevant information. In sharp contrast, genomes of microbes and viruses are incomparably more compact, with most of the genetic material assigned to distinct biological functions. However, even in these genomes, the specific genome organization (gene order) is poorly conserved. The results of comparative genomics lead to the conclusion that the genome architecture is not a straightforward result of continuous adaptation but rather is determined by the balance between the selection pressure, that is itself dependent on the effective population size and mutation rate, the level of recombination, and the activity of selfish elements. Although genes and, in many cases, multigene regions of genomes possess elaborate architectures that ensure regulation of expression, these arrangements are evolutionarily volatile and typically change substantially even on short evolutionary scales when gene sequences diverge minimally. Thus, the observed genome architectures are, mostly, products of neutral processes or epiphenomena of more general selective processes, such as selection for genome streamlining in successful lineages with large populations. Selection for specific gene arrangements (elements of genome architecture) seems only to modulate the results of these processes.     

Evidence for Fisher's dominance theory: how many 'special cases'?

Dominance, its genetic basis and evolution has been at the heart of one of the most intense controversies in the history of genetics. For more than eighty years the existence of dominance modifiers, genetic elements controlling dominance-recessivity interactions, has been suggested as a theoretical possibility, but the modifier elements themselves have remained elusive. A recent study of the self-incompatibility locus in flowering plants provided the first empirical evidence for such genetic elements: small non-coding RNAs that control dominance-recessivity by mediating methylation of the promoter of the recessive allele. Theory has shown that several biological situations are favorable for the evolution of dominance modifiers. We argue that the elucidation of this mechanism of dominance opens up new research avenues that could lead to uncovering dominance modifiers in other genetic systems, such as genes controlling Batesian and Müllerian mimicry or host-parasite interactions, thereby shedding light on the generality of the proposed mechanism.     

The evolution of sex determination in isopod crustaceans

Sex is determined by non-Mendelian genetic elements overriding the sex factors carried by the heterochromosomes in some species of terrestrial isopods. A bacterium Wolbachia and a non-bacterial feminizing factor (f) can both force chromosomal males of Armadillidium vulgare to become phenotypic functional females. The f factor is believed to be a genetic element derived from the Wolbachia genome that becomes inserted into the host nuclear genome. The feminizing factors can be considered to be selfish genetic elements because they bias their host's sex ratio to increase their own transmission. New sex-determining genes are selected (genes resisting the feminizing effects, or the transmission of feminizing elements) as a consequence of the conflict between these elements and the rest of the host's genome. These events drive the sex-determining mechanisms to evolve, and may explain the polymorphism of sex factors and the poor differentiation of the heterochromosomes in isopods.     

The struggle for life of the genome's selfish architects

Abstract  

Transposable elements (TEs) were first discovered more than 50 years ago, but were totally ignored for a long time. Over the last few decades they have gradually attracted increasing interest from research scientists. Initially they were viewed as totally marginal and anecdotic, but TEs have been revealed as potentially harmful parasitic entities, ubiquitous in genomes, and finally as unavoidable actors in the diversity, structure, and evolution of the genome. Since Darwin's theory of evolution, and the progress of molecular biology, transposable elements may be the discovery that has most influenced our vision of (genome) evolution. In this review, we provide a synopsis of what is known about the complex interactions that exist between transposable elements and the host genome. Numerous examples of these interactions are provided, first from the standpoint of the genome, and then from that of the transposable elements. We also explore the evolutionary aspects of TEs in the light of post-Darwinian theories of evolution.     

B chromosomes in plants: escapees from the A chromosome genome?

B chromosomes are dispensable elements that do not recombine with the A chromosomes of the regular complement and that follow their own evolutionary track. In some cases, they are known to be nuclear parasites with autonomous modes of inheritance, exploiting "drive" to ensure their survival in populations. Their "selfishness" brings them into conflict with their host nuclear genome and generates a host-parasite relationship, with anti-B-chromosome genes working to ameliorate the worst of their excesses in depriving their hosts of genetic resources. Molecular studies are homing in on their sequence organization to give us an insight into the origin and evolution of these enigmatic chromosomes, which are, with rare exceptions, without active genes.     

Competition between Transposable Elements and Mutator Genes in Bacteria

Although both genotypes with elevated mutation rate (mutators) and mobilization of insertion sequence (IS) elements have substantial impact on genome diversification, their potential interactions are unknown. Moreover, the evolutionary forces driving gradual accumulation of these elements are unclear: Do these elements spread in an initially transposon-free bacterial genome as they enable rapid adaptive evolution? To address these issues, we inserted an active IS1 element into a reduced Escherichia coli genome devoid of all other mobile DNA. Evolutionary laboratory experiments revealed that IS elements increase mutational supply and occasionally generate variants with especially large phenotypic effects. However, their impact on adaptive evolution is small compared with mismatch repair mutator alleles, and hence, the latter impede the spread of IS-carrying strains. Given their ubiquity in natural populations, such mutator alleles could limit early phase of IS element evolution in a new bacterial host. More generally, our work demonstrates the existence of an evolutionary conflict between mutation-promoting mechanisms.     

Fluorescence in situ hybridization to chromosomes as a tool to understand human and primate genome evolution

For the last 15 years molecular cytogenetic techniques have been extensively used to study primate evolution. Molecular probes were helpful to distinguish mammalian chromosomes and chromosome segments on the basis of their DNA content rather than solely on morphological features such as banding patterns. Various landmark rearrangements have been identified for most of the nodes in primate phylogeny while chromosome banding still provides helpful reference maps. Fluorescence in situ hybridization (FISH) techniques were used with probes of different complexity including chromosome painting probes, probes derived from chromosome sub-regions and in the size of a single gene. Since more recently, in silico techniques have been applied to trace down evolutionarily derived chromosome rearrangements by searching the human and mouse genome sequence databases. More detailed breakpoint analyses of chromosome rearrangements that occurred during higher primate evolution also gave some insights into the molecular changes in chromosome rearrangements that occurred in evolution. Hardly any "fusion genes" as known from chromosome rearrangements in cancer cells or dramatic "position effects" of genes transferred to new sites in primate genomes have been reported yet. Most breakpoint regions have been identified within gene poor areas rich in repetitive elements and/or low copy repeats (segmental duplications). The progress in various molecular and molecular-cytogenetic approaches including the recently launched chimpanzee genome project suggests that these new tools will have a significant impact on the further understanding of human genome evolution.     

A family of human microRNA genes from miniature inverted-repeat transposable elements

While hundreds of novel microRNA (miRNA) genes have been discovered in the last few years alone, the origin and evolution of these non-coding regulatory sequences remain largely obscure. In this report, we demonstrate that members of a recently discovered family of human miRNA genes, hsa-mir-548, are derived from Made1 transposable elements. Made1 elements are short miniature inverted-repeat transposable elements (MITEs), which consist of two 37 base pair (bp) terminal inverted repeats that flank 6 bp of internal sequence. Thus, Made1 elements are nearly perfect palindromes, and when expressed as RNA they form highly stable hairpin loops. Apparently, these Made1-related structures are recognized by the RNA interference enzymatic machinery and processed to form 22 bp mature miRNA sequences. Consistent with their origin from MITEs, hsa-mir-548 genes are primate-specific and have many potential paralogs in the human genome. There are more than 3,500 putative hsa-mir-548 target genes; analysis of their expression profiles and functional affinities suggests cancer-related regulatory roles for hsa-mir-548. Taken together, the characteristics of Made1 elements, and MITEs in general, point to a specific mechanism for the generation of numerous small regulatory RNAs and target sites throughout the genome. The evolutionary lineage-specific nature of MITEs could also provide for the generation of novel regulatory phenotypes related to species diversification. Finally, we propose that MITEs may represent an evolutionary link between siRNAs and miRNAs.     

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.