Systematic estimation of insertion dates of endogenous bornavirus-like elements in vesper bats.
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ABSTRACT:
SUBMITTER: Mukai Y
PROVIDER: S-EPMC6115245 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The repetitive landscapes of mammalian genomes typically display high Class I (retrotransposon) transposable element (TE) content, which usually comprises around half of the genome. In contrast, the Class II (DNA transposon) contribution is typically small (<3% in model mammals). Most mammalian genomes exhibit a precipitous decline in Class II activity beginning roughly 40 Ma. The first signs of more recently active mammalian Class II TEs were obtained from the little brown bat, Myotis lucifugus, and are reflected by higher genome content (~5%). To aid in determining taxonomic limits and potential impacts of this elevated Class II activity, we performed 454 survey sequencing of a second Myotis species as well as four additional taxa within the family Vespertilionidae and an outgroup species from Phyllostomidae. Graph-based clustering methods were used to reconstruct the major repeat families present in each species and novel elements were identified in several taxa. Retrotransposons remained the dominant group with regard to overall genome mass. Elevated Class II TE composition (3-4%) was observed in all five vesper bats, while less than 0.5% of the phyllostomid reads were identified as Class II derived. Differences in satellite DNA and Class I TE content are also described among vespertilionid taxa. These analyses present the first cohesive description of TE evolution across closely related mammalian species, revealing genome-scale differences in TE content within a single family.
| S-EPMC3342881 | biostudies-literature
Project description:Bats are ecologically diverse vertebrates characterized by their ability to host a wide range of viruses without apparent illness and the presence of numerous endogenous viral elements (EVEs). EVEs are well preserved, expressed, and may affect host biology and immunity, but their role in bat immune system evolution remains unclear. Among EVEs, endogenous bornavirus-like elements (EBLs) are bornavirus sequences integrated into animal genomes. Here, we identified a novel EBL in the microbat Myotis daubentonii, EBLL-Cultervirus.10-MyoDau (short name is CV.10-MyoDau) that shows protein-level conservation with the L-protein of a Cultervirus (Wuhan sharpbelly bornavirus). Surprisingly, we discovered a transcript on the antisense strand comprising three exons, which we named AMCR-MyoDau. The active transcription in Myotis daubentonii tissues of AMCR-MyoDau, confirmed by RNA-Seq analysis and RT-PCR, highlights its potential role during viral infections. Using comparative genomics comprising 63 bat genomes, we demonstrate nucleotide-level conservation of CV.10-MyoDau and AMCR-MyoDau across various bat species and its detection in 22 Yangochiropera and 12 Yinpterochiroptera species. To the best of our knowledge, this marks the first occurrence of a conserved EVE shared among diverse bat species, which is accompanied by a conserved antisense transcript. This highlights the need for future research to explore the role of EVEs in shaping the evolution of bat immunity.
| S-EPMC11360350 | biostudies-literature
Project description:Endogenous bornavirus-like nucleoprotein elements (EBLNs), the nucleotide sequence elements derived from the nucleoprotein gene of ancient bornavirus-like viruses, have been identified in many animal genomes. Here we show evidence that EBLNs encode functional proteins in their host. Some afrotherian EBLNs were observed to have been maintained for more than 83.3 million years under negative selection. Splice variants were expressed from the genomic loci of EBLNs in elephant, and some were translated into proteins. The EBLN proteins appeared to be localized to the rough endoplasmic reticulum in African elephant cells, in contrast to the nuclear localization of bornavirus N. These observations suggest that afrotherian EBLNs have acquired a novel function in their host. Interestingly, genomic sequences of the first exon and its flanking regions in these EBLN loci were homologous to those of transmembrane protein 106B (TMEM106B). The upstream region of the first exon in the EBLN loci exhibited a promoter activity, suggesting that the ability of these EBLNs to be transcribed in the host cell was gained through capturing a partial duplicate of TMEM106B. In conclusion, our results strongly support for exaptation of EBLNs to encode host proteins in afrotherians.
| S-EPMC4982594 | biostudies-literature
Project description:Human endogenous retroviruses (HERVs) and other long terminal repeat (LTR)-type retrotransposons (HERV/LTRs) have regulatory elements that possibly influence the transcription of host genes. We systematically identified and characterized these regulatory elements based on publicly available datasets of ChIP-Seq of 97 transcription factors (TFs) provided by ENCODE and Roadmap Epigenomics projects. We determined transcription factor-binding sites (TFBSs) using the ChIP-Seq datasets and identified TFBSs observed on HERV/LTR sequences (HERV-TFBSs). Overall, 794,972 HERV-TFBSs were identified. Subsequently, we identified "HERV/LTR-shared regulatory element (HSRE)," defined as a TF-binding motif in HERV-TFBSs, shared within a substantial fraction of a HERV/LTR type. HSREs could be an indication that the regulatory elements of HERV/LTRs are present before their insertions. We identified 2,201 HSREs, comprising specific associations of 354 HERV/LTRs and 84 TFs. Clustering analysis showed that HERV/LTRs can be grouped according to the TF binding patterns; HERV/LTR groups bounded to pluripotent TFs (e.g., SOX2, POU5F1, and NANOG), embryonic endoderm/mesendoderm TFs (e.g., GATA4/6, SOX17, and FOXA1/2), hematopoietic TFs (e.g., SPI1 (PU1), GATA1/2, and TAL1), and CTCF were identified. Regulatory elements of HERV/LTRs tended to locate nearby and/or interact three-dimensionally with the genes involved in immune responses, indicating that the regulatory elements play an important role in controlling the immune regulatory network. Further, we demonstrated subgroup-specific TF binding within LTR7, LTR5B, and LTR5_Hs, indicating that gains or losses of the regulatory elements occurred during genomic invasions of the HERV/LTRs. Finally, we constructed dbHERV-REs, an interactive database of HERV/LTR regulatory elements (http://herv-tfbs.com/). This study provides fundamental information in understanding the impact of HERV/LTRs on host transcription, and offers insights into the transcriptional modulation systems of HERV/LTRs and ancestral HERVs.
| S-EPMC5529029 | biostudies-literature
Project description:Endogenous retroviruses (ERVs) are sequences in animal genomes that originated from ancient retrovirus infections; they provide genetic novelty in hosts by being coopted as functional genes or elements during evolution. Recently, we demonstrated that endogenous elements from not only from retroviruses but also nonretroviral RNA viruses are a possible source of functional genes in host animals. The remnants of ancient bornavirus infections, called endogenous bornavirus-like elements (EBLs), are present in the genomes of a wide variety of vertebrate species, and some express functional products in host cells. Previous studies have predicted that the human EBL locus derived from bornavirus nucleoprotein, termed hsEBLN-2, expresses mRNA encoding a protein, suggesting that hsEBLN-2 has acquired a cellular function during evolution. However, the detailed function of the hsEBLN-2-derived product remains to be elucidated. In this study, we show that the hsEBLN-2-derived protein E2 acts as a mitochondrial protein that interacts with mitochondrial host factors associated with apoptosis, such as HAX-1. We also demonstrate that knockdown of hsEBLN-2-derived RNA increased the levels of PARP and caspase-3 cleavage and markedly decreased cell viability. In contrast, overexpression of E2 enhanced cell viability, as well as the intracellular stability of HAX-1, under stress conditions. Our results suggest that hsEBLN-2 has been coopted as a host gene, the product of which is involved in cell viability by interacting with mitochondrial proteins. IMPORTANCE Our genomes contain molecular fossils of ancient viruses, called endogenous virus elements (EVEs). Mounting evidence suggests that EVEs derived from nonretroviral RNA viruses have acquired functions in host cells during evolution. Previous studies have revealed that a locus encoding a bornavirus-derived EVE, hsEBLN-2, which was generated approximately 43 million years ago in a human ancestor, may be linked to the development of some tumors. However, the function of hsEBLN-2 has not been determined. In this study, we found that the E2 protein, an expression product of hsEBLN-2, interacts with apoptosis-related host proteins as a mitochondrial protein and affects cell viability. This study suggests that nonretroviral RNA viral EVEs have been coopted by hosts with more diverse functions than previously thought, showing a pivotal role for RNA virus infection in evolution.
| S-EPMC8223945 | biostudies-literature
Project description:Phylogenetic analysis supports horizontal transmission as a driving force of the spread of avian bornaviruses
| PRJEB14885 | ENA
Project description:Integration into the nuclear genome of germ line cells can lead to vertical inheritance of retroviral genes as host alleles. For other viruses, germ line integration has only rarely been documented. Nonetheless, we identified endogenous viral elements (EVEs) derived from ten non-retroviral families by systematic in silico screening of animal genomes, including the first endogenous representatives of double-stranded RNA, reverse-transcribing DNA, and segmented RNA viruses, and the first endogenous DNA viruses in mammalian genomes. Phylogenetic and genomic analysis of EVEs across multiple host species revealed novel information about the origin and evolution of diverse virus groups. Furthermore, several of the elements identified here encode intact open reading frames or are expressed as mRNA. For one element in the primate lineage, we provide statistically robust evidence for exaptation. Our findings establish that genetic material derived from all known viral genome types and replication strategies can enter the animal germ line, greatly broadening the scope of paleovirological studies and indicating a more significant evolutionary role for gene flow from virus to animal genomes than has previously been recognized.
| S-EPMC2987831 | biostudies-literature
Project description:BackgroundMinimisation of the delay to diagnosis is critical to achieving optimal outcomes for HIV patients and to limiting the potential for further onward infections. However, investigation of diagnosis delay is hampered by the fact that in most newly diagnosed patients the exact timing of infection cannot be determined and so inferences must be drawn from biomarker data.MethodsWe develop a Bayesian statistical model to evaluate delay-to-diagnosis distributions in HIV patients without known infection date, based on viral sequence genetic diversity and longitudinal viral load and CD4 count data. The delay to diagnosis is treated as a random variable for each patient and their biomarker data are modelled relative to the true time elapsed since infection, with this dependence used to obtain a posterior distribution for the delay to diagnosis. Data from a national seroconverter cohort with infection date known to within ± 6 months, linked to a database of viral sequences, are used to calibrate the model parameters. An exponential survival model is implemented that allows general inferences regarding diagnosis delay and pooling of information across groups of patients. If diagnoses are only observed within a given window period, then it is necessary to also model incidence as a function of time; we suggest a pragmatic approach to this problem when dealing with data from an established epidemic. The model developed is used to investigate delay-to-diagnosis distributions in men who have sex with men diagnosed with HIV in London in the period 2009-2013 with unknown date of infection.ResultsCross-validation and simulation analyses indicate that the models developed provide more accurate information regarding the timing of infection than does CD4 count-based estimation. Delay-to-diagnosis distributions were estimated in the London cohort, and substantial differences were observed according to ethnicity.ConclusionThe combination of all available biomarker data with pooled estimation of the distribution of diagnosis-delays allows for more precise prediction of the true timing of infection in individual patients, and the models developed also provide useful population-level information.
| S-EPMC6020319 | biostudies-literature
Project description:Animal genomes contain endogenous viral sequences, such as endogenous retroviruses and retrotransposons. Recently, we and others discovered that nonretroviral viruses also have been endogenized in many vertebrate genomes. Bornaviruses belong to the Mononegavirales and have left endogenous fragments, called "endogenous bornavirus-like elements" (EBLs), in the genomes of many mammals. The striking features of EBLs are that they contain relatively long ORFs which have high sequence homology to the extant bornavirus proteins. Furthermore, some EBLs derived from bornavirus nucleoprotein (EBLNs) have been shown to be transcribed as mRNA and probably are translated into proteins. These features lead us to speculate that EBLs may function as cellular coopted genes. An EBLN element in the genome of the thirteen-lined ground squirrel (Ictidomys tridecemlineatus), itEBLN, encodes an ORF with 77% amino acid sequence identity to the current bornavirus nucleoprotein. In this study, we cloned itEBLN from the ground squirrel genome and investigated its involvement in Borna disease virus (BDV) replication. Interestingly, itEBLN, but not a human EBLN, colocalized with the viral factory in the nucleus and appeared to affect BDV polymerase activity by being incorporated into the viral ribonucleoprotein. Our data show that, as do certain endogenous retroviruses, itEBLN potentially may inhibit infection by related exogenous viruses in vivo.
| S-EPMC4246967 | biostudies-literature
Project description:We solved the crystal structure of human ARGONAUTE1 (hAGO1) bound to endogenous 5'-phosphorylated guide RNAs. To identify structural changes that evolutionarily rendered hAGO1 inactive, we compared our structure with published structures of guide-RNA-containing and cleavage-active hAGO2. Aside from mutation of a catalytic tetrad residue, proline residues at positions 670 and 675 in hAGO1 introduce a kink in the cS7 loop and thereby forming a convex surface within the hAGO1 nucleic-acid-binding channel near the inactive catalytic site. We predicted that even upon restoration of the catalytic tetrad, hAGO1-cS7 sterically hinders the placement of a fully-paired guide-target RNA duplex into the endonuclease active site. Consistent with this hypothesis, reconstitution of the catalytic tetrad (R805H) led to low level hAGO1 cleavage activity, whereas combining R805H with cS7 substitutions (P670S and P675Q) substantially augmented hAGO1 activity. Evolutionary changes to hAGO1 were subtle and readily reversible, suggesting that loading of guide RNA and seed-based miRNA-target RNA pairing constrain its sequence drift. Structure-guided design of mutations that confer slicer activity to hAGO1. RNAs were isolated from recombinant purified hAGO1 and hAGO2, processed from baculovirus-infected Trichoplusia ni insect cells, and then processed for Illumina HiSeq. In addition, total RNA samples from AGO1 baculouvirus infected vs. non-infected Trichoplusia ni cells were isolated and also processed for Illumina HiSeq.
2013-06-20 | E-GEOD-48076 | biostudies-arrayexpress