Mark Blaxter

The University of Edinburgh, Edinburgh, Scotland, United Kingdom

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Publications (217)1394.57 Total impact

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    ABSTRACT: In mammalian systems RNA can move between cells via vesicles. Here we demonstrate that the gastrointestinal nematode Heligmosomoides polygyrus, which infects mice, secretes vesi-cles containing microRNAs (miRNAs) and Y RNAs as well as a nematode Argonaute protein. These vesicles are of intestinal origin and are enriched for homologues of mammalian exo-some proteins. Administration of the nematode exosomes to mice suppresses Type 2 innate responses and eosinophilia induced by the allergen Alternaria. Microarray analysis of mouse cells incubated with nematode exosomes in vitro identifies Il33r and Dusp1 as suppressed genes, and Dusp1 can be repressed by nematode miRNAs based on a reporter assay. We further identify miRNAs from the filarial nematode Litomosoides sigmodontis in the serum of infected mice, suggesting that miRNA secretion into host tissues is conserved among parasitic nematodes. These results reveal exosomes as another mechanism by which helminths manipulate their hosts and provide a mechanistic framework for RNA transfer between animal species.
    Nature Communications 11/2014; 5(5488). · 10.74 Impact Factor
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    ABSTRACT: The Oxford Nanopore MinION device represents a unique sequencing technology. As a mobile sequencing device powered by the USB port of a laptop, the MinION has huge potential applications. To enable these applications, the bioinformatics community will need to design and build a suite of tools specifically for MinION data.
    Bioinformatics (Oxford, England). 08/2014;
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    Mark Blaxter, Georgios Koutsovoulos
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    ABSTRACT: SUMMARY Nematodes are abundant and diverse, and include many parasitic species. Molecular phylogenetic analyses have shown that parasitism of plants and animals has arisen at least 15 times independently. Extant nematode species also display lifestyles that are proposed to be on the evolutionary trajectory to parasitism. Recent advances have permitted the determination of the genomes and transcriptomes of many nematode species. These new data can be used to further resolve the phylogeny of Nematoda, and identify possible genetic patterns associated with parasitism. Plant-parasitic nematode genomes show evidence of horizontal gene transfer from other members of the rhizosphere, and these genes play important roles in the parasite-host interface. Similar horizontal transfer is not evident in animal parasitic groups. Many nematodes have bacterial symbionts that can be essential for survival. Horizontal transfer from symbionts to the nematode is also common, but its biological importance is unclear. Over 100 nematode species are currently targeted for sequencing, and these data will yield important insights into the biology and evolutionary history of parasitism. It is important that these new technologies are also applied to free-living taxa, so that the pre-parasitic ground state can be inferred, and the novelties associated with parasitism isolated.
    Parasitology 06/2014; · 2.36 Impact Factor
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    ABSTRACT: Filarial nematodes (superfamily Filarioidea) are responsible for an annual global health burden of approximately 6.3 million disability-adjusted life-years, which represents the greatest single component of morbidity attributable to helminths affecting humans. No vaccine exists for the major filarial diseases, lymphatic filariasis and onchocerciasis; in part because research on protective immunity against filariae has been constrained by the inability of the human parasitic species to complete their lifecycles in laboratory mice. However, the rodent filaria Litomosoides sigmodontis has become a popular experimental model, as BALB/c mice are fully permissive for its development and reproduction. Here, we provide a comprehensive analysis of excretory-secretory products from L. sigmodontis across five lifecycle stages and identifications of host proteins associated with first-stage larvae (microfilariae) in the blood. Applying intensity-based quantification, we determined the abundance of 302 unique excretory-secretory proteins, of which 64.6% were present in quantifiable amounts only from gravid adult female nematodes. This lifecycle stage, together with immature microfilariae, released four proteins that have not previously been evaluated as vaccine candidates: a predicted 28.5 kDa filaria-specific protein, a zonadhesin and SCO-spondin-like protein, a vitellogenin, and a protein containing six metridin-like ShK toxin domains. Female nematodes also released two proteins derived from the obligate Wolbachia symbiont. Notably, excretory-secretory products from all parasite stages contained several uncharacterised members of the transthyretin-like protein family. Furthermore, biotin labelling revealed that redox proteins and enzymes involved in purinergic signalling were enriched on the adult nematode cuticle. Comparison of the L. sigmodontis adult secretome with that of the human-infective filarial nematode Brugia malayi (reported previously in three independent published studies) identified differences that suggest a considerable underlying diversity of potential immunomodulators. The molecules identified in L. sigmodontis excretory-secretory products show promise not only for vaccination against filarial infections, but for the amelioration of allergy and autoimmune diseases.
    Molecular &amp Cellular Proteomics 06/2014; 13:2527–2544. · 7.25 Impact Factor
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    ABSTRACT: Wolbachia are common endosymbionts of terrestrial arthropods, and are also found in nematodes: the animal-parasitic filaria, and the plant-parasite Radopholus similis. Lateral transfer of Wolbachia DNA to the host genome is common. We generated a draft genome sequence for the strongyloidean nematode parasite Dictyocaulus viviparus, the cattle lungworm. In the assembly, we identified nearly 1 Mb of sequence with similarity to Wolbachia. The fragments were unlikely to derive from a live Wolbachia infection: most were short, and the genes were disabled through inactivating mutations. Many fragments were co-assembled with definitively nematode-derived sequence. We found limited evidence of expression of the Wolbachia-derived genes. The D. viviparus Wolbachia genes were most similar to filarial strains and strains from the host-promiscuous clade F. We conclude that D. viviparus was infected by Wolbachia in the past, and that clade F-like symbionts may have been the source of filarial Wolbachia infections.
    PLoS Genetics 06/2014; 10(6):e1004397. · 8.52 Impact Factor
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    ABSTRACT: Transposable elements can be categorised into DNA and RNA elements based on their mechanism of transposition. Tyrosine recombinase elements (YREs) are relatively rare and poorly understood, despite sharing characteristics with both DNA and RNA elements. Previously, the Nematoda have been reported to have a substantially different diversity of YREs compared to other animal phyla: the Dirs1-like YRE retrotransposon was encountered in most animal phyla but not in Nematoda, and a unique Pat1-like YRE retrotransposon has only been recorded from Nematoda. We explored the diversity of YREs in Nematoda by sampling broadly across the phylum and including 34 genomes representing the three classes within Nematoda. We developed a method to isolate and classify YREs based on both feature organization and phylogenetic relationships in an open and reproducible workflow. We also ensured that our phylogenetic approach to YRE classification identified truncated and degenerate elements, informatively increasing the number of elements sampled. We identified Dirs1-like elements (thought to be absent from Nematoda) in the nematode classes Enoplia and Dorylaimia indicating that nematode model species do not adequately represent the diversity of transposable elements in the phylum. Nematode Pat1-like elements were found to be a derived form of another PAT element that is present more widely in animals. Several sequence features used widely for the classification of YREs were found to be homoplasious, highlighting the need for a phylogenetically-based classification scheme. Nematode model species do not represent the diversity of transposable elements in the phylum.
    PloS one. 04/2014; 9(9).
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    Proceedings of the Royal Society B: Biological Sciences 03/2014; 281(1783):20133076. · 5.68 Impact Factor
  • Mark Blaxter
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    ABSTRACT: The handover from maternal to zygotic control has to be carefully orchestrated. In most animal embryos, maternal products drive early embryogenesis, and the genome of the zygote is only switched on later. However, in the nematode Ascaris the zygotic genome is never silent, and the maternal products are rapidly eliminated.
    Current biology: CB 01/2014; 24(2):R72-5. · 10.99 Impact Factor
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    ABSTRACT: Next-generation sequencing (NGS) technologies have dramatically expanded the breadth of genomics. Genome-scale data, once restricted to a small number of biomedical model organisms, can now be generated for virtually any species at remarkable speed and low cost. Yet non-model organisms often lack a suitable reference to map sequence reads against, making alignment-based quality control (QC) of NGS data more challenging than cases where a well-assembled genome is already available. Here we show that by generating a rapid, non-optimized draft assembly of raw reads, it is possible to obtain reliable and informative QC metrics, thus removing the need for a high quality reference. We use benchmark datasets generated from control samples across a range of genome sizes to illustrate that QC inferences made using draft assemblies are broadly equivalent to those made using a well-established reference, and describe QC tools routinely used in our production facility to assess the quality of NGS data from non-model organisms.
    Frontiers in Genetics 01/2014; 5:111.
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    ABSTRACT: Anguillicola crassus is a swim bladder nematode of eels. The parasite is native to the Asian eel Anguilla japonica, but was introduced to Europe and the European eel Anguilla anguilla in the early 1980s. A Taiwanese source has been proposed for this introduction. In the new host in the recipient area, the parasite appears to be more pathogenic. As a reason for these differences, genetically fixed differences in infectivity and development between Taiwanese and European A.crassus have been described and disentangled from plasticity induced by different host environments. To explore whether transcriptional regulation is involved in these lifecycle differences, we have analysed a "common garden", cross infection experiment, using deep-sequencing transcriptomics. Surprisingly, in the face of clear phenotypic differences in life history traits, we identified no significant differences in gene expression between parasite populations or between experimental host species. From 120,000 SNPs identified in the transcriptome data we found that European A. crassus were not a genetic subset of the Taiwanese nematodes sampled. The loci that have the major contribution to the European-Taiwanese population differentiation show an enrichment of synonymous and non-coding polymorphism. This argues against positive selection in population differentiation. However, genes involved in protein processing in the endoplasmatic reticulum membrane and genes bearing secretion signal sequences were enriched in the set of genes most differentiated between European and Taiwanese A. crassus. These genes could be a source for the phenotypically visible genetically fixed differences between European and Taiwanese A. crassus.
    PeerJ. 01/2014; 2:e684.
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    ABSTRACT: The genetics of development in the nematode Caenorhabditis elegans has been described in exquisitedetail. The phylum Nematoda has two classes: Chromadorea (which includes C. elegans) and theEnoplea. While the development of many chromadorean species resembles closely that of C. elegans,enoplean nematodes show markedly different patterns of early cell division and cell fate assignment.Embryogenesis of the enoplean Romanomermis culicivorax has been studied in detail, but the geneticcircuitry underpinning development in this species has not been explored. We generated a draft genome for R. culicivorax and compared its gene content with that of C. elegans,a second enoplean, the vertebrate parasite Trichinella spiralis, and a representative arthropod,Tribolium castaneum. This comparison revealed that R. culicivorax has retained components of theconserved ecdysozoan developmental gene toolkit lost in C. elegans. T. spiralis has independentlylost even more of this toolkit than has C. elegans. However, the C. elegans toolkit is not simply depauperate, as many novel genes essential for embryogenesis in C. elegans are not found in, or haveonly extremely divergent homologues in R. culicivorax and T. spiralis. Our data imply fundamentaldifferences in the genetic programmes not only for early cell specification but also others such asvulva formation and sex determination. Despite the apparent morphological conservatism, major differences in the molecular logic of developmenthave evolved within the phylum Nematoda. R. culicivorax serves as a tractable system to contrast C. elegans and understand how divergent genomic and thus regulatory backgrounds nevertheless generate a conserved phenotype. The R. culicivorax draft genome will promote use of this species as a research model.
    BMC Genomics 12/2013; 14(1):923. · 4.40 Impact Factor
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    ABSTRACT: The roles of Biological Resource Centres (BRCs), such as the Culture Collection of Algae and Protozoa (CCAP), have extended beyond their traditional maintenance and provision of curated microorganisms to the user community. A major driver for change has been the exponential increase in metagenomics and environmental sequencing data over the last few years. This has underlined a critical requirement for molecular information on reference biological materials, which would allow better taxonomic interpretation, greater biological understanding and additional exploitation of these data. This is especially relevant for the relatively poorly studied protists (algal/autotrophic as well as heterotrophic) and prokaryotic cyanobacteria, which despite their huge biodiversity, reflected in the genomic data that has been generated, are underrepresented in BRCs worldwide. Here we describe the functionalities of the Culture Collection of Algae and Protozoa (CCAP) KnowledgeBase (http://www.ccap.ac.uk), developed as a one-stop shop for quality-controlled biological material, hyperlinked to manually curated molecular, bibliographic and taxonomic information. This has been built around the CCAP live collection, which constitutes one of the most genotypically diverse collections in the world with representatives of all the major eukaryotic lineages and the cyanobacteria.
    Systematics and Biodiversity 12/2013; 11(4):407-413. · 1.88 Impact Factor
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    Martin Jones, Mark Blaxter
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    ABSTRACT: Next-generation DNA sequencing technologies have made it possible to generate transcriptome data for novel organisms quickly and cheaply, to the extent that the effort required to annotate and publish a new transcriptome is greater than the effort required to sequence it. Often, following publication, details of the annotation effort are only available in summary form, hindering subsequent exploitation of the data. To promote best-practice in annotation and to ensure that data remain accessible, we have written afterParty, a web application that allows users to assemble, annotate and publish novel transcriptomes using only a web browser. afterParty is a robust web application that implements best-practice transcriptome assembly, annotation, browsing, searching, and visualization. Users can turn a collection of reads (from Roche 454 chemistry) or assembled contigs (from any sequencing chemistry, including Illumina Solexa RNA-Seq) into a searchable, browsable transcriptome resource and quickly make it publicly available. Contigs are functionally annotated based on similarity to known sequences and protein domains. Once assembled and annotated, transcriptomes derived from multiple species or libraries can be compared and searched. afterParty datasets can either be created using the existing afterParty server, or using local instances that can be built easily using a virtual machine. afterParty includes powerful visualization tools for transcriptome dataset exploration and uses a flexible annotation architecture which will allow additional types of annotation to be added in the future. afterParty's main use case scenario is one in which a working biologist has generated a large volume of transcribed sequence data and wishes to turn it into a useful resource that has some durability. By reducing the effort, bioinformatics skills, and computational resources needed to annotate and publish a transcriptome, afterParty will facilitate the annotation and sharing of sequence data that would otherwise remain unavailable. A typical metazoan transcriptome containing several tens of thousands of contigs can be annotated in a few minutes of interactive time and a few days of computational time.
    BMC Bioinformatics 10/2013; 14(1):301. · 3.02 Impact Factor
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    ABSTRACT: Most speciation events probably occur gradually, without complete and immediate reproductive isolation, but the full extent of gene flow between diverging species has rarely been characterized on a genome-wide scale. Documenting the extent and timing of admixture between diverging species can clarify the role of geographic isolation in speciation. Here we use new methodology to quantify admixture at different stages of divergence in Heliconius butterflies, based on whole genome sequences of 31 individuals. Comparisons between sympatric and allopatric populations of H. melpomene, H. cydno and H. timareta revealed a genome-wide trend of increased shared variation in sympatry, indicative of pervasive interspecific gene flow. Up to 40% of 100 kb genomic windows clustered by geography rather than by species, demonstrating that a very substantial fraction of the genome has been shared between sympatric species. Analyses of genetic variation shared over different time intervals suggested that admixture between these species has continued since early in speciation. Alleles shared between species during recent time intervals displayed higher levels of linkage disequilibrium than those shared over longer time intervals, suggesting that this admixture took place at multiple points during divergence and is probably ongoing. The signal of admixture was significantly reduced around loci controlling divergent wing patterns, as well as throughout the Z chromosome, consistent with strong selection for Müllerian mimicry and with known Z-linked hybrid incompatibility. Overall these results show that species divergence can occur in the face of persistent and genome-wide admixture over long periods of time.
    Genome Research 09/2013; · 14.40 Impact Factor
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    ABSTRACT: Wolbachia, endosymbiotic bacteria of the order Rickettsiales, are widespread in arthropods but also present in nematodes. In arthropods, A and B supergroup Wolbachia are generally associated with distortion of host reproduction. In filarial nematodes, including some human parasites, multiple lines of experimental evidence indicate that C and D supergroup Wolbachia are essential for the survival of the host, and here the symbiotic relationship is considered mutualistic. The origin of this mutualistic endosymbiosis is of interest for both basic and applied reasons: How does a parasite become a mutualist? Could intervention in the mutualism aid in treatment of human disease? Correct rooting and high-quality resolution of Wolbachia relationships are required to resolve this question. However, because of the large genetic distance between Wolbachia and the nearest outgroups, and the limited number of genomes so far available for large-scale analyses, current phylogenies do not provide robust answers. We therefore sequenced the genome of the D supergroup Wolbachia endosymbiont of Litomosoides sigmodontis, revisited the selection of loci for phylogenomic analyses, and performed a phylogenomic analysis including available complete genomes (from isolates in supergroups A, B, C and D). Using ninety orthologous genes with reliable phylogenetic signals, we obtained a robust phylogenetic reconstruction, including a highly supported root to the Wolbachia phylogeny between an (A+B) clade and a (C+D) clade. While we currently lack data from several Wolbachia supergroups, notably F, our analysis supports a model wherein the putatively mutualist endosymbiotic relationship between Wolbachia and nematodes originated from a single transition event.
    Genome Biology and Evolution 08/2013; · 4.76 Impact Factor
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    Ben Elsworth, Martin Jones, Mark Blaxter
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    ABSTRACT: High quality draft genomes are now easy to generate, as sequencing and assembly costs have dropped dramatically. However, building a user friendly, searchable website and database for a newly annotated genome is not straightforward. Here we present Badger, a lightweight and easy-to-install genome exploration environment designed for next generation, non-model organism genomes. Badger is released under the GPL and is available at http://badger.bio.ed.ac.uk/. We show two working examples: (1) a test dataset included with the source code and (2) a collection of four filarial nematode genomes. mark.blaxter@ed.ac.uk.
    Bioinformatics 08/2013; · 5.47 Impact Factor
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    Amy H Buck, Mark Blaxter
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    ABSTRACT: In the last decade, many diverse RNAi (RNA interference) pathways have been discovered that mediate gene silencing at epigenetic, transcriptional and post-transcriptional levels. The diversity of RNAi pathways is inherently linked to the evolution of Ago (Argonaute) proteins, the central protein component of RISCs (RNA-induced silencing complexes). An increasing number of diverse Agos have been identified in different species. The functions of most of these proteins are not yet known, but they are generally assumed to play roles in development, genome stability and/or protection against viruses. Recent research in the nematode Caenorhabditis elegans has expanded the breadth of RNAi functions to include transgenerational epigenetic memory and, possibly, environmental sensing. These functions are inherently linked to the production of secondary siRNAs (small interfering RNAs) that bind to members of a clade of WAGOs (worm-specific Agos). In the present article, we review briefly what is known about the evolution and function of Ago proteins in eukaryotes, including the expansion of WAGOs in nematodes. We postulate that the rapid evolution of WAGOs enables the exceptional functional plasticity of nematodes, including their capacity for parasitism.
    Biochemical Society Transactions 08/2013; 41(4):881-6. · 2.59 Impact Factor
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    ABSTRACT: Meloidogyne root knot nematodes (RKN) can infect most of the world's agricultural crop species and are among the most important of all plant pathogens. As yet however we have little understanding of their origins or the genomic basis of their extreme polyphagy. The most damaging pathogens reproduce by mitotic parthenogenesis and are suggested to originate by interspecific hybridizations between unknown parental taxa. We sequenced the genome of the diploid meiotic parthenogen Meloidogyne floridensis, and use a comparative genomic approach to test the hypothesis that it was involved in the hybrid origin of the tropical mitotic parthenogen M. incognita. Phylogenomic analysis of gene families from M. floridensis, M. incognita and an outgroup species M. hapla was used to trace the evolutionary history of these species' genomes, demonstrating that M. floridensis was one of the parental species in the hybrid origins of M. incognita. Analysis of the M. floridensis genome revealed many gene loci present in divergent copies, as they are in M. incognita, indicating that it too had a hybrid origin. The triploid M. incognita is shown to be a complex double-hybrid between M. floridensis and a third, unidentified parent. The agriculturally important RKN have very complex origins involving the mixing of several parental genomes by hybridization and their extreme polyphagy and agricultural success may be related to this hybridization, producing transgressive variation on which natural selection acts. Studying RKN variation via individual marker loci may fail due to the species' convoluted origins, and multi-species population genomics is essential to understand the hybrid diversity and adaptive variation of this important species complex. This comparative genomic analysis provides a compelling example of the importance and complexity of hybridization in generating animal species diversity more generally.
    06/2013;

Publication Stats

9k Citations
1,394.57 Total Impact Points

Institutions

  • 1996–2014
    • The University of Edinburgh
      • • Institute of Evolutionary Biology
      • • Centre for Immunity, Infection and Evolution
      • • Institute of Cell Biology
      Edinburgh, Scotland, United Kingdom
  • 2011–2013
    • University of Cambridge
      • Department of Zoology
      Cambridge, ENG, United Kingdom
    • University of Manitoba
      Winnipeg, Manitoba, Canada
    • University of Oxford
      • Sir William Dunn School of Pathology
      Oxford, ENG, United Kingdom
  • 1999–2013
    • University of Milan
      • Unitá di Patologia
      Milano, Lombardy, Italy
    • New England Biolabs
      Ipswich, Massachusetts, United States
  • 2012
    • University of Liverpool
      Liverpool, England, United Kingdom
    • University College London
      • Department of Genetics, Evolution and Environment (GEE)
      London, ENG, United Kingdom
  • 2005–2010
    • University of Nottingham
      • • Centre for Sports Medicine
      • • School of Biology
      Nottingham, ENG, United Kingdom
    • University of Toronto
      • Hospital for Sick Children
      Toronto, Ontario, Canada
  • 2009
    • SickKids
      Toronto, Ontario, Canada
  • 2008
    • University of Leicester
      • Department of Biochemistry
      Leicester, ENG, United Kingdom
  • 2004
    • University of California, Berkeley
      • Department of Integrative Biology
      Berkeley, MO, United States
  • 2002
    • Heriot-Watt University
      • Centre for Marine Biodiversity and Biotechnology
      Edinburgh, SCT, United Kingdom
  • 2000
    • Smith College
      • Biological Sciences
      Northampton, MA, United States
    • Simon Fraser University
      • Department of Biological Sciences
      Burnaby, British Columbia, Canada
  • 1996–1999
    • University of Antwerp
      Antwerpen, Flanders, Belgium
  • 1998
    • Universität Basel
      Bâle, Basel-City, Switzerland
  • 1990–1995
    • Imperial College London
      • Division of Cell and Molecular Biology
      Londinium, England, United Kingdom
  • 1994
    • Ghent University
      Gand, Flanders, Belgium