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Genome Research Jun 2024The piRNA pathway is a highly conserved mechanism to repress transposable element (TE) activity in the animal germline via a specialized class of small RNAs called...
The piRNA pathway is a highly conserved mechanism to repress transposable element (TE) activity in the animal germline via a specialized class of small RNAs called piwi-interacting RNAs (piRNAs). piRNAs are produced from discrete genomic regions called piRNA clusters (piCs). Although the molecular processes by which piCs function are relatively well understood in , much less is known about the origin and evolution of piCs in this or any other species. To investigate piC origin and evolution, we use a population genomic approach to compare piC activity and sequence composition across eight geographically distant strains of with high-quality long-read genome assemblies. We perform annotations of ovary piCs and genome-wide TE content in each strain. Our analysis uncovers extensive variation in piC activity across strains and signatures of rapid birth and death of piCs. Most TEs inferred to be recently active show an enrichment of insertions into old and large piCs, consistent with the previously proposed "trap" model of piC evolution. In contrast, a small subset of active LTR families is enriched for the formation of new piCs, suggesting that these TEs have higher proclivity to form piCs. Thus, our findings uncover processes leading to the origin of piCs. We propose that piC evolution begins with the emergence of piRNAs from individual insertions of a few select TE families prone to seed new piCs that subsequently expand by accretion of insertions from most other TE families during evolution to form larger "trap" clusters. Our study shows that TEs themselves are the major force driving the rapid evolution of piCs.
Topics: Animals; Drosophila melanogaster; RNA, Small Interfering; Female; Ovary; Evolution, Molecular; DNA Transposable Elements; Multigene Family; Piwi-Interacting RNA
PubMed: 38749655
DOI: 10.1101/gr.278062.123 -
Ecology and Evolution May 2024Large-scale barcoding projects help to aggregate information on genetic variability of multiple species throughout their ranges. Comparing DNA sequences of both...
Large-scale barcoding projects help to aggregate information on genetic variability of multiple species throughout their ranges. Comparing DNA sequences of both non-conspecific and conspecific individuals from distant parts of their ranges helps to compare level of genetic isolation-by-distance patterns in different species and adaptive types. We compared mitochondrial CO1 gene sequences of 223 spiders from Georgia (Caucasus), representing 124 species and eight families, with 3097 homological sequences from spiders mostly from Europe, but also from other parts of the World. In most families, a significant isolation-by distance pattern was observed on family level. On species level, a significant isolation-by-distance was observed in 40 species, although this low proportion is most likely related to a lack of data. Simultaneously, remarkable differences in spatial structure were shown for different species. Although the majority of the studied species have a broad western Palearctic range, web-building spiders from families Araneidae, Theridiidae, and Linyphiidae are less isolated spatially than flower spiders (Thomisidae), jumping spiders (Salticidae), wolf spiders (Lycosidae), sac spiders (Clubionidae), and ground spiders (Gnaphosidae). This pattern is related with more common ballooning in web building than in actively hunting spiders, which commonly remain isolated since preglacial time. Ground spiders build the most isolated populations in the Caucasus.
PubMed: 38742184
DOI: 10.1002/ece3.11372 -
Genome Biology May 2024Genomic regions that remain poorly understood, often referred to as the dark genome, contain a variety of functionally relevant and biologically informative features....
BACKGROUND
Genomic regions that remain poorly understood, often referred to as the dark genome, contain a variety of functionally relevant and biologically informative features. These include endogenous viral elements (EVEs)-virus-derived sequences that can dramatically impact host biology and serve as a virus fossil record. In this study, we introduce a database-integrated genome screening (DIGS) approach to investigate the dark genome in silico, focusing on EVEs found within vertebrate genomes.
RESULTS
Using DIGS on 874 vertebrate genomes, we uncover approximately 1.1 million EVE sequences, with over 99% originating from endogenous retroviruses or transposable elements that contain EVE DNA. We show that the remaining 6038 sequences represent over a thousand distinct horizontal gene transfer events across 10 virus families, including some that have not previously been reported as EVEs. We explore the genomic and phylogenetic characteristics of non-retroviral EVEs and determine their rates of acquisition during vertebrate evolution. Our study uncovers novel virus diversity, broadens knowledge of virus distribution among vertebrate hosts, and provides new insights into the ecology and evolution of vertebrate viruses.
CONCLUSIONS
We comprehensively catalog and analyze EVEs within 874 vertebrate genomes, shedding light on the distribution, diversity, and long-term evolution of viruses and reveal their extensive impact on vertebrate genome evolution. Our results demonstrate the power of linking a relational database management system to a similarity search-based screening pipeline for in silico exploration of the dark genome.
Topics: Animals; Vertebrates; Genome; Fossils; Phylogeny; Evolution, Molecular; Humans; Gene Transfer, Horizontal; Viruses; Genomics; Endogenous Retroviruses; DNA Transposable Elements
PubMed: 38741126
DOI: 10.1186/s13059-024-03258-y -
Scientific Reports May 2024SINE-VNTR-Alu (SVA) retrotransposons are transposable elements which represent a source of genetic variation. We previously demonstrated that the presence/absence of a...
SINE-VNTR-Alu (SVA) retrotransposons are transposable elements which represent a source of genetic variation. We previously demonstrated that the presence/absence of a human-specific SVA, termed SVA_67, correlated with the progression of Parkinson's disease (PD). In the present study, we demonstrate that SVA_67 acts as expression quantitative trait loci, thereby exhibiting a strong regulatory effect across the genome using whole genome and transcriptomic data from the Parkinson's progression markers initiative cohort. We further show that SVA_67 is polymorphic for its variable number tandem repeat domain which correlates with both regulatory properties in a luciferase reporter gene assay in vitro and differential expression of multiple genes in vivo. Additionally, this variation's utility as a biomarker is reflected in a correlation with a number of PD progression markers. These experiments highlight the plethora of transcriptomic and phenotypic changes associated with SVA_67 polymorphism which should be considered when investigating the missing heritability of neurodegenerative diseases.
Topics: Parkinson Disease; Humans; Disease Progression; Polymorphism, Genetic; Minisatellite Repeats; Retroelements; Alu Elements; Quantitative Trait Loci; Biomarkers; Short Interspersed Nucleotide Elements
PubMed: 38740892
DOI: 10.1038/s41598-024-61753-5 -
International Journal of Molecular... May 2024The most common form of hereditary spastic paraplegia (HSP), SPG4 is caused by single nucleotide variants and microrearrangements in the gene. The high percentage of...
The most common form of hereditary spastic paraplegia (HSP), SPG4 is caused by single nucleotide variants and microrearrangements in the gene. The high percentage of multi-exonic deletions or duplications observed in SPG4 patients is predisposed by the presence of a high frequency of sequences in the gene sequence. In the present study, we analyzed DNA and RNA samples collected from patients with different microrearrangements in to map gene breakpoints and evaluate the mutation mechanism. The study group consisted of 69 individuals, including 50 SPG4 patients and 19 healthy relatives from 18 families. Affected family members from 17 families carried varying ranges of microrearrangements in the gene, while one individual had a single nucleotide variant in the 5'UTR of . To detect the breakpoints of the gene, long-range PCR followed by sequencing was performed. The breakpoint sequence was detected for five different intragenic deletions and one duplication, revealing -mediated microhomology at breakpoint junctions resulting from non-allelic homologous recombination in these patients. Furthermore, gene expression analysis was performed using patient RNA samples extracted from whole blood. Quantitative real-time PCR tests performed in 14 patients suggest no expression of transcripts with microrearrangements in 5 of them. The obtained data indicate that nonsense-mediated decay degradation is not the only mechanism of hereditary spastic paraplegia in patients with microrearrangements.
Topics: Humans; Spastin; Spastic Paraplegia, Hereditary; Male; Female; Haploinsufficiency; Pedigree; DNA Copy Number Variations; Adult; Alu Elements; Middle Aged; Adolescent; Young Adult; Nonsense Mediated mRNA Decay
PubMed: 38732227
DOI: 10.3390/ijms25095008 -
International Journal of Molecular... Apr 2024Goose erysipelas is a serious problem in waterfowl breeding in Poland. However, knowledge of the characteristics of strains causing this disease is limited. In this...
Goose erysipelas is a serious problem in waterfowl breeding in Poland. However, knowledge of the characteristics of strains causing this disease is limited. In this study, the antimicrobial susceptibility and serotypes of four strains from domestic geese were determined, and their whole-genome sequences (WGSs) were analyzed to detect resistance genes, integrative and conjugative elements (ICEs), and prophage DNA. Sequence type and the presence of resistance genes and transposons were compared with 363 publicly available strains, as well as 13 strains of other species. Four strains tested represented serotypes 2 and 5 and the MLST groups ST 4, 32, 242, and 243. Their assembled circular genomes ranged from 1.8 to 1.9 kb with a GC content of 36-37%; a small plasmid was detected in strain 1023. Strains 1023 and 267 were multidrug-resistant. The resistance genes detected in the genome of strain 1023 were , , and s cluster, while strain 267 contained the and genes. Mutations in the gene were detected in both strains. The gene was embedded in a Tn-like transposon, which in strain 1023, together with the other resistance genes, was located on a large integrative and conjugative-like element of 130 kb designated as ICEEr1023. A minor integrative element of 74 kb was identified in strain 1012 (ICEEr1012). This work contributes to knowledge about the characteristics of bacteria and, for the first time, reveals the occurrence of and resistance genes in strains of this species. Phage infection appears to be responsible for the introduction of the gene into the genome of strain 267, while ICEs most likely play a key role in the spread of the other resistance genes identified in
Topics: Animals; Geese; Poland; Erysipelothrix; Prophages; Anti-Bacterial Agents; Erysipelothrix Infections; Poultry Diseases; Whole Genome Sequencing; Genome, Bacterial; DNA Transposable Elements; Drug Resistance, Bacterial; Conjugation, Genetic; Plasmids
PubMed: 38731857
DOI: 10.3390/ijms25094638 -
Animals : An Open Access Journal From... May 2024Avian influenza viruses (AIVs) are highly contagious respiratory viruses of birds, leading to significant morbidity and mortality globally and causing substantial... (Review)
Review
Avian influenza viruses (AIVs) are highly contagious respiratory viruses of birds, leading to significant morbidity and mortality globally and causing substantial economic losses to the poultry industry and agriculture. Since their first isolation in 2013-2014, the Asian-origin H5 highly pathogenic avian influenza viruses (HPAI) of clade 2.3.4.4b have undergone unprecedented evolution and reassortment of internal gene segments. In just a few years, it supplanted other AIV clades, and now it is widespread in the wild migratory waterfowl, spreading to Asia, Europe, Africa, and the Americas. Wild waterfowl, the natural reservoir of LPAIVs and generally more resistant to the disease, also manifested high morbidity and mortality with HPAIV clade 2.3.4.4b. This clade also caused overt clinical signs and mass mortality in a variety of avian and mammalian species never reported before, such as raptors, seabirds, sealions, foxes, and others. Most notably, the recent outbreaks in dairy cattle were associated with the emergence of a few critical mutations related to mammalian adaptation, raising concerns about the possibility of jumping species and acquisition of sustained human-to-human transmission. The main clinical signs and anatomopathological findings associated with clade 2.3.4.4b virus infection in birds and non-human mammals are hereby summarized.
PubMed: 38731377
DOI: 10.3390/ani14091372 -
Nature Communications May 2024Heteroresistance is a medically relevant phenotype where small antibiotic-resistant subpopulations coexist within predominantly susceptible bacterial populations....
Heteroresistance is a medically relevant phenotype where small antibiotic-resistant subpopulations coexist within predominantly susceptible bacterial populations. Heteroresistance reduces treatment efficacy across diverse bacterial species and antibiotic classes, yet its genetic and physiological mechanisms remain poorly understood. Here, we investigated a multi-resistant Klebsiella pneumoniae isolate and identified three primary drivers of gene dosage-dependent heteroresistance for several antibiotic classes: tandem amplification, increased plasmid copy number, and transposition of resistance genes onto cryptic plasmids. All three mechanisms imposed fitness costs and were genetically unstable, leading to fast reversion to susceptibility in the absence of antibiotics. We used a mouse gut colonization model to show that heteroresistance due to elevated resistance-gene dosage can result in antibiotic treatment failures. Importantly, we observed that the three mechanisms are prevalent among Escherichia coli bloodstream isolates. Our findings underscore the necessity for treatment strategies that address the complex interplay between plasmids, resistance cassettes, and transposons in bacterial populations.
Topics: Klebsiella pneumoniae; Animals; Anti-Bacterial Agents; Mice; Plasmids; DNA Copy Number Variations; Escherichia coli; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Gene Dosage; Klebsiella Infections; Humans; DNA Transposable Elements; Female
PubMed: 38730266
DOI: 10.1038/s41467-024-48233-0 -
The Science of the Total Environment Jul 2024Staphylococcus aureus is a versatile pathobiont, exhibiting a broad host range, including humans, other mammals, and avian species. Host specificity determinants,...
Staphylococcus aureus is a versatile pathobiont, exhibiting a broad host range, including humans, other mammals, and avian species. Host specificity determinants, virulence, and antimicrobial resistance genes are often shared by strains circulating at the animal-human interface. While transmission dynamics studies have shown strain exchange between humans and livestock, knowledge of the source, genetic diversification, and transmission drivers of S. aureus in wildlife lag behind. In this work, we explore a wide array of S. aureus genomes from different sources in the Iberian Peninsula to understand population structure, gene content and niche adaptation at the human-livestock-wildlife nexus. Through Bayesian inference, we address the hypothesis that S. aureus strains in wildlife originate from humanized landscapes, either from contact with humans or through interactions with livestock. Phylogenetic reconstruction applied to whole genome sequence data was completed with a dataset of 450 isolates featuring multiple clones from the 1990-2022 period and a subset of CC398 strains representing the 2008-2022 period. Phylodynamic signatures of S. aureus from the Iberian Peninsula suggest widespread circulation of most clones among humans before jumping to other hosts. The number of transitions of CC398 strains within each host category (human, livestock, wildlife) was high (88.26 %), while the posterior probability of transitions from livestock to wildlife was remarkably high (0.99). Microbial genome-wide association analysis did not evidence genome rearrangements nor biomarkers suggesting S. aureus niche adaptation to wildlife, thus supporting recent spill overs. Altogether, our findings indicate that S. aureus isolates collected in the past years from wildlife most likely represent multiple introduction events from livestock. The clonal origin of CC398 and its potential to disseminate and evolve through different animal host species are highlighted, calling for management practices at the livestock-wildlife axis to improve biosecurity and thus restrict S. aureus transmission and niche expansion along gradients of human influence.
Topics: Animals; Livestock; Staphylococcus aureus; Staphylococcal Infections; Animals, Wild; Spain; Humans; Phylogeny; Portugal
PubMed: 38729368
DOI: 10.1016/j.scitotenv.2024.173027 -
Nature Genetics Jun 2024Concurrent readout of sequence and base modifications from long unamplified DNA templates by Pacific Biosciences of California (PacBio) single-molecule sequencing...
Concurrent readout of sequence and base modifications from long unamplified DNA templates by Pacific Biosciences of California (PacBio) single-molecule sequencing requires large amounts of input material. Here we adapt Tn5 transposition to introduce hairpin oligonucleotides and fragment (tagment) limiting quantities of DNA for generating PacBio-compatible circular molecules. We developed two methods that implement tagmentation and use 90-99% less input than current protocols: (1) single-molecule real-time sequencing by tagmentation (SMRT-Tag), which allows detection of genetic variation and CpG methylation; and (2) single-molecule adenine-methylated oligonucleosome sequencing assay by tagmentation (SAMOSA-Tag), which uses exogenous adenine methylation to add a third channel for probing chromatin accessibility. SMRT-Tag of 40 ng or more human DNA (approximately 7,000 cell equivalents) yielded data comparable to gold standard whole-genome and bisulfite sequencing. SAMOSA-Tag of 30,000-50,000 nuclei resolved single-fiber chromatin structure, CTCF binding and DNA methylation in patient-derived prostate cancer xenografts and uncovered metastasis-associated global epigenome disorganization. Tagmentation thus promises to enable sensitive, scalable and multimodal single-molecule genomics for diverse basic and clinical applications.
Topics: Humans; DNA Methylation; Animals; Male; Prostatic Neoplasms; Mice; Sequence Analysis, DNA; Chromatin; DNA; DNA Transposable Elements; High-Throughput Nucleotide Sequencing; CpG Islands; Cell Line, Tumor; CCCTC-Binding Factor; Transposases
PubMed: 38724748
DOI: 10.1038/s41588-024-01748-0