Mycobacteriophages BPs, Angel and Halo: comparative genomics reveals a novel class of ultra-small mobile genetic elements.
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ABSTRACT:
SUBMITTER: Sampson T
PROVIDER: S-EPMC2833263 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Mycobacteriophages show promise as therapeutic agents for non-tuberculous mycobacterium infections. However, little is known about phage recognition of Mycobacterium cell surfaces or mechanisms of phage resistance. We show here that trehalose polyphleates (TPPs)-high-molecular-weight, surface-exposed glycolipids found in some mycobacterial species-are required for infection of Mycobacterium abscessus and Mycobacterium smegmatis by clinically useful phages BPs and Muddy. TPP loss leads to defects in adsorption and infection and confers resistance. Transposon mutagenesis shows that TPP disruption is the primary mechanism for phage resistance. Spontaneous phage resistance occurs through TPP loss by mutation, and some M. abscessus clinical isolates are naturally phage-insensitive due to TPP synthesis gene mutations. Both BPs and Muddy become TPP-independent through single amino acid substitutions in their tail spike proteins, and M. abscessus mutants resistant to TPP-independent phages reveal additional resistance mechanisms. Clinical use of BPs and Muddy TPP-independent mutants should preempt phage resistance caused by TPP loss.
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Project description:BACKGROUND:Cryptophytes are an ecologically important group of algae comprised of phototrophic, heterotrophic and osmotrophic species. This lineage is of great interest to evolutionary biologists because their plastids are of red algal secondary endosymbiotic origin. Cryptophytes have a clear phylogenetic affinity to heterotrophic eukaryotes and possess four genomes: host-derived nuclear and mitochondrial genomes, and plastid and nucleomorph genomes of endosymbiotic origin. RESULTS:To gain insight into cryptophyte mitochondrial genome evolution, we sequenced the mitochondrial DNAs of five species and performed a comparative analysis of seven genomes from the following cryptophyte genera: Chroomonas, Cryptomonas, Hemiselmis, Proteomonas, Rhodomonas, Storeatula and Teleaulax. The mitochondrial genomes were similar in terms of their general architecture, gene content and presence of a large repeat region. However, gene order was poorly conserved. Characteristic features of cryptophyte mtDNAs included large syntenic clusters resembling ?-proteobacterial operons that encode bacteria-like rRNAs, tRNAs, and ribosomal protein genes. The cryptophyte mitochondrial genomes retain almost all genes found in many other eukaryotes including the nad, sdh, cox, cob, and atp genes, with the exception of sdh2 and atp3. In addition, gene cluster analysis showed that cryptophytes possess a gene order closely resembling the jakobid flagellates Jakoba and Reclinomonas. Interestingly, the cox1 gene of R. salina, T. amphioxeia, and Storeatula species was found to contain group II introns encoding a reverse transcriptase protein, as did the cob gene of Storeatula species CCMP1868. CONCLUSIONS:These newly sequenced genomes increase the breadth of data available from algae and will aid in the identification of general trends in mitochondrial genome evolution. While most of the genomes were highly conserved, extensive gene arrangements have shuffled gene order, perhaps due to genome rearrangements associated with hairpin-containing mobile genetic elements, tRNAs with palindromic sequences, and tandem repeat sequences. The cox1 and cob gene sequences suggest that introns have recently been acquired during cryptophyte evolution. Comparison of phylogenetic trees based on plastid and mitochondrial genome data sets underscore the different evolutionary histories of the host and endosymbiont components of present-day cryptophytes.
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Project description:Fusarium species are among the most important phytopathogenic and toxigenic fungi. To understand the molecular underpinnings of pathogenicity in the genus Fusarium, we compared the genomes of three phenotypically diverse species: Fusarium graminearum, Fusarium verticillioides and Fusarium oxysporum f. sp. lycopersici. Our analysis revealed lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes and account for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity, indicative of horizontal acquisition. Experimentally, we demonstrate the transfer of two LS chromosomes between strains of F. oxysporum, converting a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in F. oxysporum. These findings put the evolution of fungal pathogenicity into a new perspective.
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Project description:The evolutionary dynamics of transposable elements (TEs) are still poorly understood. One reason is that TE abundance needs to be studied at the population level, but sequencing individuals on a population scale is still too expensive to characterize TE abundance in multiple populations. Although sequencing pools of individuals dramatically reduces sequencing costs, a comparison of TE abundance between pooled samples has been difficult, if not impossible, due to various biases. Here, we introduce a novel bioinformatic tool, PoPoolationTE2, which is specifically tailored for the comparison of TE abundance among pooled population samples or different tissues. Using computer simulations, we demonstrate that PoPoolationTE2 not only faithfully recovers TE insertion frequencies and positions but, by homogenizing the power to identify TEs across samples, it provides an unbiased comparison of TE abundance between pooled population samples. We anticipate that PoPoolationTE2 will greatly facilitate the analysis of TE insertion patterns in a broad range of applications.
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Project description:The discovery and mapping of cis-regulatory elements is important for understanding regulation of gene transcription in mosquito vectors of human diseases. Genome sequence data are available for 3 species, Aedes aegypti, Anopheles gambiae, and Culex quinquefasciatus (Diptera: Culicidae), representing 2 subfamilies (Culicinae and Anophelinae) that are estimated to have diverged 145 to 200 million years ago. Comparative genomics tools were used to screen genomic DNA fragments located in the 5'-end flanking regions of orthologous genes. These analyses resulted in the identification of 137 sequences, designated "mosquito motifs," 7 to 9 nucleotides in length, representing 18 families of putative cis-regulatory elements conserved significantly among the 3 species when compared to the fruit fly, Drosophila melanogaster. Forty-one of the motifs were implicated previously in experiments as sites for binding transcription factors or functioning in the regulation of mosquito gene expression. Further analyses revealed associations between specific motifs and expression profiles, particularly in those genes that show increased or decreased mRNA abundance in females following a blood meal, and those accumulating transcription products exclusively or preferentially in the midgut, fat bodies, or ovaries. These results validate the methodology and support a relationship between the discovered motifs and the conservation of hematophagy in mosquitoes.
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Project description:BackgroundThe strand-biased circularizing integrative elements (SEs) are putatively non-mobilizable integrative elements for transmitting antimicrobial resistance genes. The transposition mode and the prevalence of SEs in prokaryotes remain vague.ResultsTo corroborate the transposition mode and the prevalence of SEs, hypothetical transposition intermediates of an SE were searched for in genomic DNA fractions of an SE host. Then, the SE core genes were defined based on gene knockout experiments, and the synteny blocks of their distant homologs were searched for in the RefSeq complete genome sequence database using PSI-BLAST. A genomic DNA fractionation experiment revealed that SE copies are present in a double-stranded nicked circular form in vivo. Operonic structure of three conserved coding sequences (intA, tfp, intB) and srap located at the left end of SEs were identified as essential for attL × attR recombination. The synteny blocks of tfp and srap homologs were detected in 3.6% of the replicons of Gammaproteobacteria but not in other taxa, implying that SE movement is host-dependent. SEs have been discovered most frequently in the orders Vibrionales (19% of replicons), Pseudomonadales (18%), Alteromonadales (17%), and Aeromonadales (12%). Genomic comparisons revealed 35 new SE members with identifiable termini. SEs are present at 1 to 2 copies per replicon and have a median length of 15.7 kb. Three newly identified SE members carry antimicrobial resistance genes, like tmexCD-toprJ, mcr-9, and blaGMA-1. Further experiments validated that three new SE members possess the strand-biased attL × attR recombination activity.ConclusionsThis study suggested that transposition intermediates of SEs are double-stranded circular DNA. The main hosts of SEs are a subset of free-living Gammaproteobacteria; this represents a rather narrow host range compared to those of mobile DNA element groups discovered to date. As the host range, genetic organization, and movements are unique among the mobile DNA elements, SEs provide a new model system for host-mobile DNA element coevolution studies.
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Project description:To generate data for comparative analyses of zygomycete mitochondrial gene expression, we sequenced mtDNAs of three distantly related zygomycetes, Rhizopus oryzae, Mortierella verticillata and Smittium culisetae. They all contain the standard fungal mitochondrial gene set, plus rnpB, the gene encoding the RNA subunit of the mitochondrial RNase P (mtP-RNA) and rps3, encoding ribosomal protein S3 (the latter lacking in R.oryzae). The mtP-RNAs of R.oryzae and of additional zygomycete relatives have the most eubacteria-like RNA structures among fungi. Precise mapping of the 5' and 3' termini of the R.oryzae and M.verticillata mtP-RNAs confirms their expression and processing at the exact sites predicted by secondary structure modeling. The 3' RNA processing of zygomycete mitochondrial mRNAs, SSU-rRNA and mtP-RNA occurs at the C-rich sequence motifs similar to those identified in fission yeast and basidiomycete mtDNAs. The C-rich motifs are included in the mature transcripts, and are likely generated by exonucleolytic trimming of RNA 3' termini. Zygomycete mtDNAs feature a variety of insertion elements: (i) mtDNAs of R.oryzae and M.verticillata were subject to invasions by double hairpin elements; (ii) genes of all three species contain numerous mobile group I introns, including one that is closest to an intron that invaded angiosperm mtDNAs; and (iii) at least one additional case of a mobile element, characterized by a homing endonuclease insertion between partially duplicated genes [Paquin,B., Laforest,M.J., Forget,L., Roewer,I., Wang,Z., Longcore,J. and Lang,B.F. (1997) Curr. Genet., 31, 380-395]. The combined mtDNA-encoded proteins contain insufficient phylogenetic signal to demonstrate monophyly of zygomycetes.
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Project description:Xylella fastidiosa causes diseases in many plant species. Originally confined to the Americas, infecting mainly grapevine, citrus, and coffee, X. fastidiosa has spread to several plant species in Europe causing devastating diseases. Many pathogenicity and virulence factors have been identified, which enable the various X. fastidiosa strains to successfully colonize the xylem tissue and cause disease in specific plant hosts, but the mechanisms by which this happens have not been fully elucidated. Here we present thorough comparative analyses of 94 whole-genome sequences of X. fastidiosa strains from diverse plant hosts and geographic regions. Core-genome phylogeny revealed clades with members sharing mostly a geographic region rather than a host plant of origin. Phylogenetic trees for 1605 orthologous CDSs were explored for potential candidates related to host specificity using a score of mapping metrics. However, no candidate host-specificity determinants were strongly supported using this approach. We also show that X. fastidiosa accessory genome is represented by an abundant and heterogeneous mobilome, including a diversity of prophage regions. Our findings provide a better understanding of the diversity of phylogenetically close genomes and expand the knowledge of X. fastidiosa mobile genetic elements and immunity systems.
| S-EPMC9148166 | biostudies-literature
Project description:BackgroundRecent advances in the accumulation of genetic mapping and DNA sequence information from several salmonid species support the long standing view of an autopolyploid origin of these fishes (i.e., 4R). However, the paralogy relationships of the chromosomal segments descendent from earlier polyploidization events (i.e., 2R/3R) largely remain unknown, mainly due to an unbalanced pseudogenization of paralogous genes that were once resident on the ancient duplicated segments. Inter-specific conserved noncoding elements (CNE) might hold the key in identifying these regions, if they are associated with arrays of genes that have been highly conserved in syntenic blocks through evolution. To test this hypothesis, we investigated the chromosomal positions of subset of CNE in the rainbow trout genome using a comparative genomic framework.ResultsThrough a genome wide analysis, we selected 41 pairs of adjacent CNE located on various chromosomes in zebrafish and obtained their intervening, less conserved, sequence information from rainbow trout. We identified 56 distinct fragments corresponding to about 150 Kbp of sequence data that were localized to 67 different chromosomal regions in the rainbow trout genome. The genomic positions of many duplicated CNE provided additional support for some previously suggested homeologies in this species. Additionally, we now propose 40 new potential paralogous affinities by analyzing the variation in the segregation patterns of some multi-copy CNE along with the synteny association comparison using several model vertebrates. Some of these regions appear to carry signatures of the 1R, 2R or 3R duplications. A subset of these CNE markers also demonstrated high utility in identifying homologous chromosomal segments in the genomes of Atlantic salmon and Arctic charr.ConclusionCNE seem to be more efficacious than coding sequences in providing insights into the ancient paralogous affinities within the vertebrate genomes. Such a feature makes these elements extremely attractive for comparative genomics studies, as they can be treated as 'anchor' markers to investigate the association of distally located candidate genes on the homologous genomic segments of closely or distantly related organisms.
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