Precise genotyping of circular mobile elements from metagenomic data uncovers human-associated plasmids with recent common ancestors.
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ABSTRACT:
SUBMITTER: Shalon N
PROVIDER: S-EPMC9104695 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The genealogies of different genetic loci vary in depth. The deeper the genealogy, the greater the chance that it will include a rare event, such as the insertion of a mobile element. Therefore, the genealogy of a region that contains a mobile element is on average older than that of the rest of the genome. In a simple demographic model, the expected time to most recent common ancestor (TMRCA) is doubled if a rare insertion is present. We test this expectation by examining single nucleotide polymorphisms around polymorphic Alu insertions from two completely sequenced human genomes. The estimated TMRCA for regions containing a polymorphic insertion is two times larger than the genomic average (P < <10(-30)), as predicted. Because genealogies that contain polymorphic mobile elements are old, they are shaped largely by the forces of ancient population history and are insensitive to recent demographic events, such as bottlenecks and expansions. Remarkably, the information in just two human DNA sequences provides substantial information about ancient human population size. By comparing the likelihood of various demographic models, we estimate that the effective population size of human ancestors living before 1.2 million years ago was 18,500, and we can reject all models where the ancient effective population size was larger than 26,000. This result implies an unusually small population for a species spread across the entire Old World, particularly in light of the effective population sizes of chimpanzees (21,000) and gorillas (25,000), which each inhabit only one part of a single continent.
| S-EPMC2836654 | biostudies-literature
Project description:Extrachromosomal mobile genetic elements (eMGEs), including phages and plasmids, that can move across different microbes, play important roles in genome evolution and shaping the structure of microbial communities. However, we still know very little about eMGEs, especially their abundances, distributions and putative functions in microbiomes. Thus, a comprehensive description of eMGEs is of great utility. Here we present mMGE, a comprehensive catalog of 517 251 non-redundant eMGEs, including 92 492 plasmids and 424 759 phages, derived from diverse body sites of 66 425 human metagenomic samples. About half the eMGEs could be further grouped into 70 074 clusters using relaxed criteria (referred as to eMGE clusters below). We provide extensive annotations of the identified eMGEs including sequence characteristics, taxonomy affiliation, gene contents and their prokaryotic hosts. We also calculate the prevalence, both within and across samples for each eMGE and eMGE cluster, enabling users to see putative associations of eMGEs with human phenotypes or their distribution preferences. All eMGE records can be browsed or queried in multiple ways, such as eMGE clusters, metagenomic samples and associated hosts. The mMGE is equipped with a user-friendly interface and a BLAST server, facilitating easy access/queries to all its contents easily. mMGE is freely available for academic use at: https://mgedb.comp-sysbio.org.
| S-EPMC7778953 | biostudies-literature
Project description:Transposon Tn7 is notable for the control it exercises over where transposition events are directed. One Tn7 integration pathways recognizes a highly conserved attachment (att) site in the chromosome, while a second pathway specifically recognizes mobile plasmids that facilitate transfer of the element to new hosts. In this review, I discuss newly discovered families of Tn7-like elements with different targeting pathways. Perhaps the most exciting examples are multiple instances where Tn7-like elements have repurposed CRISPR/Cas systems. In these cases, the CRISPR/Cas systems have lost their canonical defensive function to destroy incoming mobile elements; instead, the systems have been naturally adapted to use guide RNAs to specifically direct transposition into these mobile elements. The new families of Tn7-like elements also include a variety of novel att sites in bacterial chromosomes where genome islands can form. Interesting families have also been revealed where proteins described in the prototypic Tn7 element are fused or otherwise repurposed for the new dual activities. This expanded understanding of Tn7-like elements broadens our view of how genetic systems are repurposed and provides potentially exciting new tools for genome modification and genomics. Future opportunities and challenges to understanding the impact of the new families of Tn7-like elements are discussed.
| S-EPMC6904524 | biostudies-literature
Project description:Metagenomic approaches are widespread in microbiological research, but so far, the knowledge on extrachromosomal DNA diversity and composition has largely remained dependant on cultivating host organisms. Even with the emergence of metagenomics, complete circular sequences are rarely identified, and have required manual curation. We propose a robust in silico procedure for identifying complete small plasmids in metagenomic datasets from whole genome shotgun sequencing. From one very pure and exhaustively sequenced metamobilome from rat cecum, we identified a total of 616 circular sequences, 160 of which were carrying a gene with plasmid replication domain. Further homology analyses indicated that the majority of these plasmid sequences are novel. We confirmed the circularity of the complete plasmid candidates using an inverse-type PCR approach on a subset of sequences with 95% success, confirming the existence and length of discrete sequences. The implication of these findings is a broadened understanding of the traits of circular elements in nature and the possibility of massive data mining in existing metagenomic datasets to discover novel pools of complete plasmids thus vastly expanding the current plasmid database.
| S-EPMC3913684 | biostudies-literature
Project description:BackgroundElucidating the ecological and biological identity of extrachromosomal mobile genetic elements (eMGEs), such as plasmids and bacteriophages, in the human gut remains challenging due to their high complexity and diversity.ResultsHere, we show efficient identification of eMGEs as complete circular or linear contigs from PacBio long-read metagenomic data. De novo assembly of PacBio long reads from 12 faecal samples generated 82 eMGE contigs (2.5~666.7-kb), which were classified as 71 plasmids and 11 bacteriophages, including 58 novel plasmids and six bacteriophages, and complete genomes of five diverse crAssphages with terminal direct repeats. In a dataset of 413 gut metagenomes from five countries, many of the identified plasmids were highly abundant and prevalent. The ratio of gut plasmids by our plasmid data is more than twice that in the public database. Plasmids outnumbered bacterial chromosomes three to one on average in this metagenomic dataset. Host prediction suggested that Bacteroidetes-associated plasmids predominated, regardless of microbial abundance. The analysis found several plasmid-enriched functions, such as inorganic ion transport, while antibiotic resistance genes were harboured mostly in low-abundance Proteobacteria-associated plasmids.ConclusionsOverall, long-read metagenomics provided an efficient approach for unravelling the complete structure of human gut eMGEs, particularly plasmids.
| S-EPMC6712665 | biostudies-literature
Project description:Mobilome of hyperthermophilic archaea dwelling in deep-sea hydrothermal vents is poorly characterized. To gain insight into genetic diversity and dynamics of mobile genetic elements in these environments we have sequenced five new plasmids from different Thermococcus strains that have been isolated from geographically remote hydrothermal vents. The plasmids were ascribed to two subfamilies, pTN2-like and pEXT9a-like. Gene content and phylogenetic analyses illuminated a robust connection between pTN2-like plasmids and Pyrococcus abyssi virus 1 (PAV1), with roughly half of the viral genome being composed of genes that have homologues in plasmids. Unexpectedly, pEXT9a-like plasmids were found to be closely related to the previously sequenced plasmid pMETVU01 from Methanocaldococcus vulcanius M7. Our data suggests that the latter observation is most compatible with an unprecedented horizontal transfer of a pEXT9a-like plasmid from Thermococcales to Methanococcales. Gene content analysis revealed that thermococcal plasmids encode Hfq-like proteins and toxin-antitoxin (TA) systems of two different families, VapBC and RelBE. Notably, although abundant in archaeal genomes, to our knowledge, TA and hfq-like genes have not been previously found in archaeal plasmids or viruses. Finally, the plasmids described here might prove to be useful in developing new genetic tools for hyperthermophiles.
| S-EPMC3543421 | biostudies-literature
Project description:Ancestry analysis from genetic data plays a critical role in studies of human disease and evolution. Recent work has introduced explicit models for the geographic distribution of genetic variation and has shown that such explicit models yield superior accuracy in ancestry inference over nonmodel-based methods. Here we extend such work to introduce a method that models admixture between ancestors from multiple sources across a geographic continuum. We devise efficient algorithms based on hidden Markov models to localize on a map the recent ancestors (e.g., grandparents) of admixed individuals, joint with assigning ancestry at each locus in the genome. We validate our methods by using empirical data from individuals with mixed European ancestry from the Population Reference Sample study and show that our approach is able to localize their recent ancestors within an average of 470 km of the reported locations of their grandparents. Furthermore, simulations from real Population Reference Sample genotype data show that our method attains high accuracy in localizing recent ancestors of admixed individuals in Europe (an average of 550 km from their true location for localization of two ancestries in Europe, four generations ago). We explore the limits of ancestry localization under our approach and find that performance decreases as the number of distinct ancestries and generations since admixture increases. Finally, we build a map of expected localization accuracy across admixed individuals according to the location of origin within Europe of their ancestors.
| S-EPMC4267945 | biostudies-literature
Project description:BackgroundClostridium botulinum strains can be divided into four physiological groups that are sufficiently diverged to be considered as separate species. Here we present the first complete genome of a C. botulinum strain from physiological group III, causing animal botulism. We also compare the sequence to three new draft genomes from the same physiological group.ResultsThe 2.77 Mb chromosome was highly conserved between the isolates and also closely related to that of C. novyi. However, the sequence was very different from the human C. botulinum group genomes. Replication-directed translocations were rare and conservation of synteny was high. The largest difference between C. botulinum group III isolates occurred within their surprisingly large plasmidomes and in the pattern of mobile elements insertions. Five plasmids, constituting 13.5% of the total genetic material, were present in the completed genome. Interestingly, the set of plasmids differed compared to other isolates. The largest plasmid, the botulinum-neurotoxin carrying prophage, was conserved at a level similar to that of the chromosome while the medium-sized plasmids seemed to be undergoing faster genetic drift. These plasmids also contained more mobile elements than other replicons. Several toxins and resistance genes were identified, many of which were located on the plasmids.ConclusionsThe completion of the genome of C. botulinum group III has revealed it to be a genome with dual identity. It belongs to the pathogenic species C. botulinum, but as a genotypic species it should also include C. novyi and C. haemolyticum. The genotypic species share a conserved chromosomal core that can be transformed into various pathogenic variants by modulation of the highly plastic plasmidome.
| S-EPMC3098183 | biostudies-literature
Project description:qnrD is a plasmid mediated quinolone resistance gene from unknown origin, recently described in Enterobacteriaceae. It encodes a pentapeptide repeat protein 36-60% different from the other Qnr (A, B, C, S and VC). Since most qnrD-positive strains were described as strains belonging to Proteus or Providencia genera, we hypothesized that qnrD originated in Proteeae before disseminating to other enterobacterial species. We screened 317 strains of Proteeae for qnrD and its genetic support by PCR. For all the seven qnrD-positive strains (4 Proteus mirabilis, 1 Proteus vulgaris and 2 Providencia rettgeri) the gene was carried onto a small non-transmissible plasmid, contrarily to other qnr genes that are usually carried onto large multi-resistant plasmids. Nucleotide sequences of the qnrD-bearing plasmids were 96% identical. Plasmids contained 3 ORFs apart from qnrD and belonged to an undescribed incompatibility group. Only one plasmid, in P. vulgaris, was slightly different with a 1,568-bp insertion between qnrD and its promoter, leading to absence of quinolone resistance. We sought for similar plasmids in 15 reference strains of Proteeae, but which were tested negative for qnrD, and found a 48% identical plasmid (pVERM) in Providencia vermicola. In order to explain how qnrD could have been inserted into such native plasmid, we sought for gene mobilization structures. qnrD was found to be located within a mobile insertion cassette (mic) element which sequences are similar to one mic also found in pVERM. Our conclusions are that (i) the small non-transmissible qnrD-plasmids described here may result from the recombination between an as-yet-unknown progenitor of qnrD and pVERM, (ii) these plasmids are maintained in Proteeae being a qnrD reservoir (iii) the mic element may explain qnrD mobilization from non-transmissible plasmids to mobilizable or conjugative plasmids from other Enterobacteriaceae, (iv) they can recombined with larger multiresistant plasmids conjugated in Proteeae.
| S-EPMC3913671 | biostudies-literature
Project description:Antibiotic resistance genes (ARGs) are undergoing a remarkably rapid geographic expansion in various ecosystems, including pristine environments such as Antarctica. The study of ARGs and environmental resistance genes (ERGs) mechanisms could provide a better understanding of their origin, evolution, and dissemination in these pristine environments. Here, we describe the diversity of ARGs and ERGs and the importance of mobile genetic elements as a possible mechanism for the dissemination of resistance genes in Antarctica. We analyzed five soil metagenomes from Deception Island in Antarctica. Results showed that detected ARGs are associated with mechanisms such as antibiotic efflux, antibiotic inactivation, and target alteration. On the other hand, resistance to metals, surfactants, and aromatic hydrocarbons were the dominant ERGs. The taxonomy of ARGs showed that Pseudomonas, Psychrobacter, and Staphylococcus could be key taxa for studying antibiotic resistance and environmental resistance to stress in Deception Island. In addition, results showed that ARGs are mainly associated with phage-type mobile elements suggesting a potential role in their dissemination and prevalence. Finally, these results provide valuable information regarding the ARGs and ERGs in Deception Island including the potential contribution of mobile genetic elements to the spread of ARGs and ERGs in one of the least studied Antarctic ecosystems to date.
| S-EPMC9320737 | biostudies-literature