Mark Blaxter

The University of Edinburgh, Edinburgh, Scotland, United Kingdom

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Publications (260)1638.41 Total impact

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    ABSTRACT: Transposable elements (TEs) are a major source of genome variation across the branches of life. Although TEs may occasionally play an adaptive role in their host's genome, they are much more often deleterious, and purifying selection is thus an important factor controlling genomic TE loads. In contrast, life history and genomic characteristics such as mating system, parasitism, GC content, and RNAi pathways, have been suggested to account for the startling disparity of TE loads in different species. Previous studies of fungal, plant, and animal genomes have reported conflicting results regarding the direction in which these genomic features drive TE evolution. Many of these studies have had limited power because they studied taxonomically narrow systems, comparing only a limited number of phylogenetically independent contrasts, and did not address long term effects on TE evolution. Here we explicitly test the long term determinants of TE evolution by comparing 42 nematode genomes that span over 500 million years of diversification, and include numerous transitions between life history states and RNAi pathways. We have analysed the reconstructed TE loads of ancestors through the Nematoda phylogeny to account for correlation with GC content and transitions in TE evolutionary models. We also analysed the effect of transitions in life history characteristics and RNAi using ANOVA of phylogenetically independent contrasts. We show that purifying selection against TEs is the dominant force throughout the evolutionary history of Nematoda, as indicated by reconstructed ancestral TE loads, and that strong stochastic Ornstein-Uhlenbeck processes are the underlying models which best explain TE diversification among extant species. In contrast we found no evidence that life history or RNAi variations have a significant influence upon genomic TE load across extended periods of evolutionary history. We suggest that these are largely inconsequential to the large differences in TE content observed between genomes and only by these large-scale comparisons can we distinguish long term and persistent effects from transient effects or misleading random changes.
    Full-text · Article · Dec 2015
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    ABSTRACT: Wolbachia pipientis is possibly the most widespread endosymbiont of arthropods and nematodes. While all Wolbachia strains have historically been defined as a single species, 16 monophyletic clusters of diversity (called supergroups) have been described. Different supergroups have distinct host ranges and symbiotic relationships, ranging from mutualism to reproductive manipulation. In filarial nematodes, which include parasites responsible for major diseases of humans (such as Onchocerca volvulus, agent of river blindness) and companion animals (Dirofilaria immitis, the dog heartworm), Wolbachia has an obligate mutualist role and is the target of new treatment regimens. Here, we compare the genomes of eight Wolbachia strains, spanning the diversity of the major supergroups (A-F), analysing synteny, transposable element content, GC skew and gene loss or gain. We detected genomic features that differ between Wolbachia supergroups, most notably in the C and D clades from filarial nematodes. In particular, strains from supergroup C (symbionts of O. volvulus and D. immitis) present a pattern of GC skew, conserved synteny and lack of transposable elements, unique in the Wolbachia genus. These features could be the consequence of a distinct symbiotic relationship between C Wolbachia strains and their hosts, highlighting underappreciated differences between the mutualistic supergroups found within filarial nematodes.
    Full-text · Article · Dec 2015 · Open Biology
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    ABSTRACT: Background Second and third generation sequencing technologies have revolutionised bacterial genomics. Short-read Illumina reads result in cheap but fragmented assemblies, whereas longer reads are more expensive but result in more complete genomes. The Oxford Nanopore MinION device is a revolutionary mobile sequencer that can produce thousands of long, single molecule reads. Results We sequenced Bacteroides fragilis strain BE1 using both the Illumina MiSeq and Oxford Nanopore MinION platforms. We were able to assemble a single chromosome of 5.18 Mb, with no gaps, using publicly available software and commodity computing hardware. We identified gene rearrangements and the state of invertible promoters in the strain. Conclusions The single chromosome assembly of Bacteroides fragilis strain BE1 was achieved using only modest amounts of data, publicly available software and commodity computing hardware. This combination of technologies offers the possibility of ultra-cheap, high quality, finished bacterial genomes.
    Full-text · Article · Dec 2015
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    ABSTRACT: Distinct populations of the potato cyst nematode (PCN) Globodera pallida exist in the UK that differ in their ability to overcome various sources of resistance. An efficient method for distinguishing between populations would enable pathogen-informed cultivar choice in the field. Science and Advice for Scottish Agriculture (SASA) annually undertake national DNA diagnostic tests to determine the presence of PCN in potato seed and ware land by extracting DNA from soil floats. These DNA samples provide a unique resource for monitoring the distribution of PCN and further interrogation of the diversity within species. We identify a region of mitochondrial DNA descriptive of three main groups of G. pallida present in the UK and adopt a metagenetic approach to the sequencing and analysis of all SASA samples simultaneously. Using this approach, we describe the distribution of G. pallida mitotypes across Scotland with field-scale resolution. Most fields contain a single mitotype, one-fifth contain a mix of mitotypes, and less than 3% contain all three mitotypes. Within mixed fields, we were able to quantify the relative abundance of each mitotype across an order of magnitude. Local areas within mixed fields are dominated by certain mitotypes and indicate towards a complex underlying 'pathoscape'. Finally, we assess mitotype distribution at the level of the individual cyst and provide evidence of 'hybrids'. This study provides a method for accurate, quantitative and high-throughput typing of up to one thousand fields simultaneously, while revealing novel insights into the national genetic variability of an economically important plant parasite.
    Full-text · Article · Nov 2015 · Molecular Ecology
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    ABSTRACT: Three strikingly different alternative male mating morphs (aggressive 'independents', semicooperative 'satellites' and female-mimic 'faeders') coexist as a balanced polymorphism in the ruff, Philomachus pugnax, a lek-breeding wading bird. Major differences in body size, ornamentation, and aggressive and mating behaviors are inherited as an autosomal polymorphism. We show that development into satellites and faeders is determined by a supergene consisting of divergent alternative, dominant and non-recombining haplotypes of an inversion on chromosome 11, which contains 125 predicted genes. Independents are homozygous for the ancestral sequence. One breakpoint of the inversion disrupts the essential CENP-N gene (encoding centromere protein N), and pedigree analysis confirms the lethality of homozygosity for the inversion. We describe new differences in behavior, testis size and steroid metabolism among morphs and identify polymorphic genes within the inversion that are likely to contribute to the differences among morphs in reproductive traits.
    Full-text · Article · Nov 2015 · Nature Genetics
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    ABSTRACT: Linking the evolution of the phenotype to the underlying genotype is a key aim of evolutionary genetics and is crucial to our understanding of how natural selection shapes a trait. Here we consider the genetic basis of sex allocation behaviour in the parasitoid wasp Nasonia vitripennis using a transcriptomics approach. Females allocate offspring sex in line with Local Mate Competition (LMC) theory. Female-biased sex ratios are produced when one or few females lay eggs on a patch. As the number of females contributing offspring to a patch increases, less female-biased sex ratios are favoured. We contrasted the transcriptomic responses of females as they oviposit under conditions known to influence sex allocation: foundress number (a social cue) and the state of the host (parasitised or not). We found, that when females encounter other females on a patch, or assess host quality with their ovipositors, the resulting changes in sex allocation is not associated with significant changes in whole-body gene expression. We also found that the gene expression changes produced by females, as they facultatively allocate sex in response to a host cue and a social cue, are very closely correlated. We expanded the list of candidate genes associated with oviposition behaviour in Nasonia, some of which may be involved in fundamental processes underlying the ability to facultatively allocate sex, including sperm storage and utilisation.
    Full-text · Article · Oct 2015 · G3-Genes Genomes Genetics
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    Amir Szitenberg · Max John · Mark L. Blaxter · David H. Lunt
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    ABSTRACT: The reproducibility of experiments is key to the scientific process, and particularly necessary for accurate reporting of analyses in data-rich fields such as phylogenomics. We present ReproPhylo, a phylogenomic analysis environment developed to ensure experimental reproducibility, to facilitate the handling of large-scale data, and to assist methodological experimentation. Reproducibility, and instantaneous repeatability, is built in to the ReproPhylo system and does not require user intervention or configuration because it stores the experimental workflow as a single, serialized Python object containing explicit provenance and environment information. This 'single file' approach ensures the persistence of provenance across iterations of the analysis, with changes automatically managed by the version control program Git. This file, along with a Git repository, are the primary reproducibility outputs of the program. In addition, ReproPhylo produces an extensive human-readable report and generates a comprehensive experimental archive file, both of which are suitable for submission with publications. The system facilitates thorough experimental exploration of both parameters and data. ReproPhylo is a platform independent CC0 Python module and is easily installed as a Docker image or a WinPython self-sufficient package, with a Jupyter Notebook GUI, or as a slimmer version in a Galaxy distribution.
    Full-text · Article · Sep 2015 · PLoS Computational Biology
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    ABSTRACT: An RNA-seq experiment with 48 biological replicates in each of 2 conditions was performed to determine the number of biological replicates (n_r) required, and to identify the most effective statistical analysis tools for identifying differential gene expression (DGE). When n_r=3, seven of the nine tools evaluated give true positive rates (TPR) of only 20 to 40 percent. For high fold-change genes (|log2(FC)|>2) the TPR is >85 percent. Two tools performed poorly; over- or under-predicting the number of differentially expressed genes. Increasing replication gives a large increase in TPR when considering all DE genes but only a small increase for high fold-change genes. Achieving a TPR >85% across all fold-changes requires n_r>20. For future RNA-seq experiments these results suggest n_r>6, rising to n_r>12 when identifying DGE irrespective of fold-change is important. For n_r>12, superior TPR makes edgeR the leading tool tested. For n_r≥12, minimizing false positives is more important and DESeq outperforms the other tools. (http://arxiv.org/abs/1505.02017)
    Full-text · Article · May 2015
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    ABSTRACT: An RNA-seq experiment with 48 biological replicates in each of 2 conditions was performed to determine the number of biological replicates ($n_r$) required, and to identify the most effective statistical analysis tools for identifying differential gene expression (DGE). When $n_r=3$, seven of the nine tools evaluated give true positive rates (TPR) of only 20 to 40 percent. For high fold-change genes ($|log_{2}(FC)|\gt2$) the TPR is $\gt85$ percent. Two tools performed poorly; over- or under-predicting the number of differentially expressed genes. Increasing replication gives a large increase in TPR when considering all DE genes but only a small increase for high fold-change genes. Achieving a TPR $\gt85$% across all fold-changes requires $n_r\gt20$. For future RNA-seq experiments these results suggest $n_r\gt6$, rising to $n_r\gt12$ when identifying DGE irrespective of fold-change is important. For $n_r\gt12$, superior TPR makes edgeR the leading tool tested. For $n_r \ge12$, minimizing false positives is more important and DESeq outperforms the other tools.
    Full-text · Article · May 2015
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    ABSTRACT: High-throughput RNA sequencing (RNA-seq) is now the standard method to determine differential gene expression. Identifying differentially expressed genes crucially depends on estimates of read count variability. These estimates are typically based on statistical models such as the negative binomial distribution, which is employed by the tools edgeR, DESeq and cuffdiff. Until now, the validity of these models has usually been tested on either low-replicate RNA-seq data or simulations. A 48-replicate RNA-seq experiment in yeast was performed and data tested against theoretical models. The observed gene read counts were consistent with both log-normal and negative binomial distributions, while the mean-variance relation followed the line of constant dispersion parameter of ~0.01. The high-replicate data also allowed for strict quality control and screening of "bad" replicates, which can drastically affect the gene read-count distribution. RNA-seq data have been submitted to ENA archive with project ID PRJEB5348. g.j.barton@dundee.ac.uk. © The Author(s) 2015. Published by Oxford University Press.
    Full-text · Article · May 2015 · Bioinformatics
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    Full-text · Dataset · May 2015
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    Full-text · Dataset · May 2015
  • Mark Blaxter · Martin Jones

    No preview · Article · May 2015 · Genome
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    Full-text · Dataset · Apr 2015
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    Full-text · Dataset · Apr 2015
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    ABSTRACT: Abstract Background The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High- quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation.
    Full-text · Article · Apr 2015 · Genome Biology
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    ABSTRACT: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. Highquality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation.
    Full-text · Article · Apr 2015 · Genome Biology
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    ABSTRACT: Author Summary Transposable elements are segments of DNA that have the ability to copy themselves independently of the host genome and thus pose a severe threat to the integrity of the genome. Organisms have evolved mechanisms to restrict the spread of transposable elements, with small RNA molecules being one of the most important defense mechanisms. In animals, the predominant small RNA transposon-silencing mechanism is the piRNA pathway, which appears to be widely conserved. However, little is known about how small RNA pathways that target transposons evolve. In order to study this question we investigated small RNA pathways across the nematode phylum, using a well-studied model organism—the nematode Caenorhabditis elegans—as the starting point. Surprisingly we found that the piRNA pathway has been completely lost in all groups of nematodes bar those most closely related to C. elegans. This finding raises the intriguing question of how these nematodes are able to control transposable element mobilization without piRNAs. We discovered that there are other small RNA pathways that target transposable elements in these nematodes, employing RNA-dependent RNA polymerases in order to make small RNAs antisense to transposable elements. Intriguingly, the most ancient of these mechanisms, found in the most basal nematodes, is a Dicer-dependent RNA-directed DNA methylation pathway. This pathway shares strong similarity to transposon-silencing mechanisms in plants and fungi, suggesting that it might have been present in an ancient common ancestor of all eukaryotes. Our results highlight the rapid evolution of small RNA pathways and demonstrate the importance of examining molecular pathways in detail across a range of evolutionary distances.
    Full-text · Article · Feb 2015 · PLoS Biology
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    ABSTRACT: microRNAs (miRNAs), a class of short, non-coding RNA can be found in a highly stable, cell-free form in mammalian body fluids. Specific miRNAs are secreted by parasitic nematodes in exosomes and have been detected in the serum of murine and dog hosts infected with the filarial nematodes Litomosoides sigmodontis and Dirofilaria immitis, respectively. Here we identify extracellular, parasite-derived small RNAs associated with Onchocerca species infecting cattle and humans. Small RNA libraries were prepared from total RNA extracted from the nodule fluid of cattle infected with Onchocerca ochengi as well as serum and plasma from humans infected with Onchocerca volvulus in Cameroon and Ghana. Parasite-derived miRNAs were identified based on the criteria that sequences unambiguously map to hairpin structures in Onchocerca genomes, do not align to the human genome and are not present in European control serum. A total of 62 mature miRNAs from 52 distinct pre-miRNA candidates were identified in nodule fluid from cattle infected with O. ochengi of which 59 are identical in the genome of the human parasite O. volvulus. Six of the extracellular miRNAs were also identified in sequencing analyses of serum and plasma from humans infected with O. volvulus. Based on sequencing analysis the abundance levels of the parasite miRNAs in serum or plasma range from 5 to 127 reads/per million total host miRNA reads identified, comparable to our previous analyses of Schistosoma mansoni and L. sigmodontis miRNAs in serum. All six of the O. volvulus miRNAs identified have orthologs in other filarial nematodes and four were identified in the serum of mice infected with L. sigmodontis. We have identified parasite-derived miRNAs associated with onchocerciasis in cattle and humans. Our results confirm the conserved nature of RNA secretion by diverse nematodes. Additional species-specific small RNAs from O. volvulus may be present in serum based on the novel miRNA sequences identified in the nodule fluid. In our analyses comparison to European control serum illuminates the scope for false-positives, warranting caution in criteria that should be applied to identification of biomarkers of infection.
    Full-text · Article · Jan 2015 · Parasites & Vectors
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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.
    Full-text · Article · Nov 2014 · PeerJ

Publication Stats

14k Citations
1,638.41 Total Impact Points

Institutions

  • 1996-2015
    • The University of Edinburgh
      • • Centre for Immunity, Infection and Evolution
      • • Institute of Evolutionary Biology
      • • School of Biological Sciences
      • • Ashworth Laboratory
      • • Institute of Cell Biology
      Edinburgh, Scotland, United Kingdom
  • 2012
    • University of Liverpool
      • Institute of Integrative Biology
      Liverpool, England, United Kingdom
  • 2011
    • University of Manitoba
      • Department of Entomology
      Winnipeg, Manitoba, Canada
    • University of Cologne
      • Zoological Institute
      Köln, North Rhine-Westphalia, Germany
  • 2005
    • University of Toronto
      • Department of Biochemistry
      Toronto, Ontario, Canada
  • 1995
    • University of Antwerp
      Antwerpen, Flanders, Belgium
  • 1990-1995
    • Imperial College London
      • Division of Cell and Molecular Biology
      Londinium, England, United Kingdom
  • 1994
    • University of Otago
      • Department of Biochemistry
      Taieri, Otago, New Zealand
  • 1992
    • Imperial Valley College
      • Department of Biology
      IPL, California, United States
  • 1988-1990
    • London School of Hygiene and Tropical Medicine
      • Department of Pathogen Molecular Biology
      Londinium, England, United Kingdom