Mobile DNA最新文献

While it is straightforward to understand why most mutations affecting functional sequence are harmful, how genomic changes result in new beneficial traits is harder to understand. Domestication of transposable elements (TEs) is an important source of both new genes and new regulatory systems as, for their own propagation, TEs need to have transcription factor binding sites and functional products that predispose to their recruitment. But are such predispositions to gain-of-function sufficient? Here we consider the case of the endogenous retrovirus, HERVH. Knockdown data supports HERVH having roles in pluripotency, self-renewal and defence against transpositionally-active retroelements in the early human embryo. We clarify the pluripotent cell types associated with HERVH expression and, in the process, note a key unresolved issue, framed by the unwanted transcript hypothesis: how can some cell types have 2% of their transcripts being HERVH-derived but survive the multiplicity of cellular devices that suppress foreign transcripts, be this by transcriptional repression or post-transcriptional filtering? We note a common coupling between novelty generation and suppression evasion. For example, pluripotency-associated KLF4 binding is thought to compete with transcriptional suppressor binding. Similarly, HERVH has a strong splice site enabling efficient novel chimeric transcript formation, the resulting exon-intron junctions enabling evasion of the unwanted transcript filters that recognize low or absent intron presence. We conclude that to better understand domestication, a focus on predispositions to avoidance of unwanted transcripts filters, as well as predispositions to gain of functions, is necessary. The same insights will be valuable for transgene design (eg for gene therapy) and instructive of gain-of-function in tumours, as HERVH is known to be involved in onco-exaptation events.

Mobile genetic elements drive bacterial evolution by promoting genetic plasticity and adaptation; among them, mycoplasma Integrative and Conjugative Elements (ICEs) challenge the notion that mycoplasmas evolved solely through genome reduction. However, they remain poorly characterized, particularly in Mycoplasma hominis, which is a human genital pathogen. In this study, we investigated the circularization, transcription, and protein expression of M. hominis 4788 ICE (ICEHo4788) under the following four environmental conditions: axenic growth, coculture with HeLa cells, mitomycin C exposure, and thermal stress. During axenic growth, ICEHo4788 circularization peaked at 12 h with a 9.4-fold increase in the number of circular forms. Mitomycin C and cold shock induced only a moderate increase in circularization (approximately 3-fold), whereas heat shock significantly reduced the number of circular forms. In coculture with HeLa cells, a strong increase in the number of circular forms was observed at 72 h and 7 days postinfection with 10- and 23-fold increases, respectively. Coculture also led to a 5- to 23-fold increase in transcription at 7 days, whereas axenic growth, mitomycin C exposure, and thermal stress did not differ. Proteomic analysis revealed that MhoH(a), CDS18, CDS17, and CDS11 were significantly overexpressed at 12 h. Neither mitomycin C nor cold shock induced changes in ICE-related proteins, but heat shock upregulated two M. hominis molecular chaperones and ICEHo4788 MhoH(a). In conclusion, environmental conditions modulate M. hominis ICE activity with strong stimulation in the presence of eukaryotic cells. These findings offer new insights into the regulation and environmental responses of M. hominis ICEs.

Transposable elements (TEs) are known to be major components of eukaryotic genomes and impact genome evolution and architecture, including in the speciose lineage of Insecta. Although new and increased efforts have allowed for more insect genomes to become available, our understanding of insect TE diversity across various lineages is poor. This lack of knowledge is especially true in the hyper-diverse Hymenoptera (including bees, ants, wasps, and sawflies) which includes some of the most beneficial insects, such as pollinators and parasitoid (parasitic) wasps. Here, we present the order-level TE composition and analyze its phylogenetic signal across the Braconidae (Hymenoptera), a very diverse lineage of parasitic wasps. Further we investigate the effect of TEs on genome size and note a positive relationship that has some distinct lineage specific differences. Despite phylogenetically conserved genome sizes within Braconidae, we found that TE abundance and diversity was not phylogenetically conserved and was highly variable across taxa, more so than what has been reported for other insect lineages. This represents the first comparative genomic analysis of TEs in a lineage of parasitic wasps and increases our understanding of the diversity of TE composition across related taxa.

Specialized transposable elements capable of generating introns, termed introners, are one of the major drivers of intron gain in eukaryotes. Horizontal transfer of transposable elements (HTT) is thought to play an important role in shaping introner distributions. Viruses could function as vehicles of introner HTT since they often integrate into host genomes and have been implicated in widespread HTT in eukaryotes. We annotated integrated viral elements in diverse dinoflagellate genomes with active introners and queried viral elements for introner sequences. We find that 25% of viral elements contain introners. The vast majority of viral elements represent maverick-polinton-like double-stranded DNA (dsDNA) viruses in the family eupolintoviridae as well as giant dsDNA viruses. By querying a previously annotated set of eupolintoviral proviruses, we show that introners populate full-length elements with machinery required for transposition as well as viral infection. Introners in the vast majority of viral elements are younger than or similar in age to others in their host genome, suggesting that most viral elements acquired introners after integration. However, a subset of viral elements shows the opposite pattern wherein viral introners are significantly older than other introners, possibly consistent with virus-to-host horizontal transfer. Together, our results suggest that dsDNA viruses may serve as vectors for HTT of introners between individuals and species, resulting in the introduction of intron-generating transposons to new lineages.

Transposable elements (TEs) have been hypothesized to play a pivotal role in driving diversification by facilitating the emergence of novel phenotypes and the accumulation of divergence between species. Hybridization and adaptation to novel niches have been proposed to destabilize mechanisms constraining TE proliferation, potentially inducing a 'TE burst' that promotes TE accumulation on the genome. The rapid speciation and ecological diversification characteristic of adaptive radiations offer a unique opportunity to examine the link between TE accumulation and speciation, diversification, hybridization and adaptation. Here, focusing on all 15 species of the genus Scalesia (Asteraceae), a radiation endemic to the Galápagos Islands, we test whether diversification, hybridization, or shifts in ecological niche are associated with changes in TE accumulation in genomes. Our analyses reveal little to no variation in TE accumulation among Scalesia species nor its hybrid populations. Shifts in ecological niches, linked to climatic variation, did not result in discernible changes in TE accumulation, a surprising finding given the anticipated selective pressure imposed by aridity, a factor often linked to genome size reduction. We found no distinct patterns in the temporal accumulation of TEs, and no effects at the class or superfamily level. Our findings suggest that while TEs may play a key role in evolution at the locus level, their macroevolutionary association with diversification or speciation appears weak. Rather than actively driving evolutionary diversification, TEs may simply be'along for the ride.

Background: Transposable Elements (TEs) represent a sizeable amount of mammalian genomes, providing regulatory sequences involved in shaping gene expression patterns. NF-Y is a Transcription factor -TF- trimer that binds to the CCAAT box, belonging to a selected group implicated in determining initiation of coding and noncoding RNAs.

Results: We focus on NF-Y TE locations in 8 human and 8 mouse cells. Binding is exclusive for retroviral LTR12, MLT1 and MER in human and RLTR10 and IAPLTR in mouse cells. Cobinding and analysis of the DNA matrices signal enrichment of distinct TFs neighboring CCAAT in the three TE classes: MAFK/F/G in LTR12 and USF1/2 in MLT1 with precise alignment of sites, PKNOX1, MEIS2, PBX2/3 TALE TFs in MER57. The presence of "epigenetic" marks in human cells indicate prevalent co-association with open chromatin in MER, closed in LTR12 and mixed in MLT1. Based on chromatin features, these locations are mostly marked as enhancers, as confirmed by analysis of loci predicted to generate eRNAs.

Conclusions: These results are discussed in the context of functional data, suggesting a complex -positive and potentially-negative role of NF-Y on distinct classes of repetitive sequences.

Human endogenous retroviruses (HERVs) occupy 8% of the human genome. Although most HERV integrations are severely degenerated by mutations, the most recently integrated proviruses, such as members of the HERV-K HML-2 subfamily, partially retain regulatory and protein-coding capacity. The precise number of HML-2 proviral copies in the modern human population is constantly changing in literature, as new integrations are being uncovered. The first comprehensive list of HML-2 proviral loci was compiled in 2011, including a total of 91 proviruses. Since then, multiple articles published additions and modifications to that list, mainly in the form of new polymorphic proviral sites, updated chromosomal band characterizations or the correspondence of coordinates in the new version of the published human reference genome. In the present study, we systematically searched the literature for lists of HML-2 proviruses and their coordinates and cross-examined every proviral locus information, also against the human genome. We gathered all available data about all HML-2 proviral integrations identified to date and updated, corrected and refined the coordinates in both human genome assemblies currently used in research, to incorporate the whole provirus in each case. Thereby we present an exhaustive (to date) catalogue of all known HML-2 proviruses and their respective coordinates, as a powerful tool for studies aiming to decipher HERV role in health and disease, especially for high-throughput data analyses, which could lead to the discovery of links between specific HERV integrations and biological mechanisms or medical disorders.

Background: Transposons are DNA sequences able to move or copy themselves to other genomic locations leading to insertional mutagenesis. Although transposon-derived sequences account for half of the human genome, most elements are no longer transposition competent. Moreover, transposons are normally repressed through epigenetic silencing in healthy adult tissues but become derepressed in several human cancers, with high activity detected in colorectal cancer. Their impact on non-malignant and malignant tissue as well as the differences between somatic and germline retrotransposition remain poorly understood. With new sequencing technologies, including long read sequencing, we can access intricacies of retrotransposition, such as insertion sequence details and nested repeats, that have been previously challenging to characterize.

Results: In this study, we investigate somatic and germline retrotransposition by analyzing long read sequencing from 56 colorectal cancers and 112 uterine leiomyomas. We identified 1495 somatic insertions in colorectal samples, while striking lack of insertions was detected in uterine leiomyomas. Our findings highlight differences between somatic and germline events, such as transposon type distribution, insertion length, and target site preference. Leveraging long-read sequencing, we provide an in-depth analysis of the twin-priming phenomenon, detecting it across transposable element types that remain active in humans, including Alus. Additionally, we detect an abundance of germline transposons in repetitive DNA, along with a relationship between replication timing and insertion target site.

Conclusions: Our study reveals a stark contrast in somatic transposon activity between colorectal cancers and uterine leiomyomas, and highlights differences between somatic and germline transposition. This suggests potentially different conditions in malignant and non-malignant tissues, as well as in germline and somatic tissues, which could be involved in the transposition process. Long-read sequencing provided important insights into transposon behavior, allowing detailed examination of structural features such as twin priming and nested elements.

Background: Within eukaryotes, most horizontal transfer of genetic material involves mobile DNA sequences and such events are called horizontal transposable element transfer (HTT). Although thousands of HTT examples have been reported, the transfer mechanisms and their impacts on host genomes remain elusive.

Results: In this work, we carefully annotated three Helitron families within several Xenopus frog genomes. One of the Helitron family, Heli1Xen1, is recurrently involved in capturing and shuffling Xenopus laevis genes required in early embryonic development. Remarkably, we found that Heli1Xen1 is seemingly expressed in X. laevis and has produced multiple genomic polymorphisms within the X. laevis population. To identify the origin of Heli1Xen1, we searched its consensus sequence against available genome assemblies. We found highly similar copies in the genomes of another 13 vertebrate species from divergent vertebrate lineages, including reptiles, ray-finned fishes and amphibians. Further phylogenetic analysis provides evidence showing that Heli1Xen1 invaded these lineages via HTT quite recently, around 0.58-10.74 million years ago.

Conclusions: The frequently Heli1Xen1-involved HTT events among reptiles, fishes and amphibians could provide insights into possible vectors for transfer, such as shared viruses across lineages. Furthermore, we propose that the Heli1Xen1 sequence could be an ideal candidate for studying the mechanism and genomic impact of Helitron transposition.

Transposons and their derivatives make up a major proportion of the human genome, but they are not just relics of ancient genomes. They can still be expressed, potentially affecting the transcription of adjacent genes, and can sometimes even contribute to their coding sequence. Active transposons can integrate into new sites in the genome, potentially modifying the expression of nearby loci and leading to genetic disorders. In this review, we highlight work exploring the expression of transposons in skeletal muscles and transcriptional regulation by the KRAB-ZFP/KAP1/SETDB1 complex. We next focus on specific cases of transposon insertion causing phenotypic variation and distinct muscular dystrophies, as well as the implication of transposon expression in immune myopathies. Finally, we discuss the dysregulation of transposons in facioscapulohumeral dystrophy and aging.