Genomics of Loa loa, a Wolbachia-free filarial parasite of humans

Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Nature Genetics (Impact Factor: 29.35). 03/2013; 45(5). DOI: 10.1038/ng.2585
Source: PubMed


Loa loa, the African eyeworm, is a major filarial pathogen of humans. Unlike most filariae, L. loa does not contain the obligate intracellular Wolbachia endosymbiont. We describe the 91.4-Mb genome of L. loa and that of the related filarial parasite Wuchereria bancrofti and predict 14,907 L. loa genes on the basis of microfilarial RNA sequencing. By comparing these genomes to that of another filarial parasite, Brugia malayi, and to those of several other nematodes, we demonstrate synteny among filariae but not with nonparasitic nematodes. The L. loa genome encodes many immunologically relevant genes, as well as protein kinases targeted by drugs currently approved for use in humans. Despite lacking Wolbachia, L. loa shows no new metabolic synthesis or transport capabilities compared to other filariae. These results suggest that the role of Wolbachia in filarial biology is more subtle than previously thought and reveal marked differences between parasitic and nonparasitic nematodes.

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Available from: Jennifer Russo Wortman, Apr 02, 2014
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    • "wCte Ctenocephalides felis SRR1222150 Raw data – – – B [36] wOo Onchocerca ochengi HE660029 Complete 1 957,990 32.1 C [24] wOv Onchocerca volvulus strain Cameroon HG810405 Complete 1 960,618 32.1 C Cotton et al. (unpublished) wDi Dirofilaria immitis PRJEB4154 a WGS 2 921,012 32.7 C [22] wBm strain TRS Brugia malayi AE017321 Complete 1 1,080,084 34.2 D [35] wBn Wuchereria bancrofti ADHD00000000 WGS 763 1,052,327 34.0 D [26] wLs Litomosoides sigmodontis PRJEB4155 a WGS 10 1,048,936 32.1 D [22] wFol Folsomia candida SRR1222159 Raw data – – – E [36] wCle Cimex lectularius AP013028 Complete 1 1,250,060 36.3 F [69] wOc Osmia caerulescens SRR1221705 Raw data – – – F [36] wMen Mengenilla moldrzyki SRX095325 WGS – – – F [68] "
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    ABSTRACT: Wolbachia are highly extended bacterial endosymbionts that infect arthropods and filarial nematodes and produce contrasting phenotypes on their hosts. Wolbachia taxonomy has been understudied. Currently, Wolbachia strains are classified into phylogenetic supergroups. Here we applied phylogenomic analyses to study Wolbachia evolutionary relationships and examined metrics derived from their genome sequences such as average nucleotide identity (ANI), in silico DNA-DNA hybridization (DDH), G+C content, and synteny to shed light on the taxonomy of these bacteria. Draft genome sequences of strains wDacA and wDacB obtained from the carmine cochineal insect Dactylopius coccus were included. Although all analyses indicated that each Wolbachia supergroup represents a distinct evolutionary lineage, we found that some of the analyzed supergroups showed enough internal heterogeneity to be considered as assemblages of more than one species. Thus, supergroups would represent supraspecific groupings. Consequently, Wolbachia pipientis nomen species would apply only to strains of supergroup B and we propose the designation of 'Candidatus Wolbachia bourtzisii', 'Candidatus Wolbachia onchocercicola', 'Candidatus Wolbachia blaxterii', 'Candidatus Wolbachia brugii', 'Candidatus Wolbachia taylorii', 'Candidatus Wolbachia collembolicola' and 'Candidatus Wolbachia multihospitis' for other supergroups. Copyright © 2015 Elsevier GmbH. All rights reserved.
    Systematic and Applied Microbiology 07/2015; 38(6). DOI:10.1016/j.syapm.2015.05.005 · 3.28 Impact Factor
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    • "We combined a bioinformatics approach with manual curation to provide improved insights into functional and structural aspects of the RIOK family of parasitic and free-living nematodes whose draft genomes are publicly available (Ghedin et al., 2007; Dieterich et al., 2008; Opperman et al., 2008; Jex et al., 2011; Mitreva et al., 2011; Desjardins et al., 2013; Laing et al., 2013; Schwarz et al., 2013; Srinivasan et al., 2013). Due to a lack of reliable culturing systems to propagate parasites in the laboratory and because current gene silencing approaches are unreliable or impractical, functional analyses of genes in parasitic nematodes of animals are challenging (Geldhof et al., 2006; Maule et al., 2011). "
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    ABSTRACT: Despite RIO kinases being essential for life, their functions, substrates and cellular pathways remain enigmatic. In the present study, gene structures were characterised for 26 RIO kinase from draft genomes of parasitic and free-living nematodes. RNA-seq transcription profiles of RIO kinase genes were investigated for selected parasitic nematodes and showed that these kinases are transcribed in developmental stages that infect their mammalian host. Three-dimensional structural models of Caenorhabditis elegans RIO kinases were predicted, and elucidated functional domains and conserved regions in nematode homologs. These findings provide prospects for functional studies of RIO kinase genes in C. elegans and an opportunity for the design and validation of nematode-specific inhibitors of these enzymes in socioeconomic parasitic worms.
    International Journal for Parasitology 07/2014; 44(11). DOI:10.1016/j.ijpara.2014.06.005 · 3.87 Impact Factor
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    • "These datasets are, therefore, a vital source of information on the genetic content and complexity of these parasites and will remain so even after draft genomes are published as genome sequencing does not, in and of itself, provide any information on AS. Historically, initial reports of draft genomes rarely comment on AS [57-64]. For instance, the draft genome of the well-studied filarial nematode B. malayi was published in 2007, but the report made no mention of AS [59]. "
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    ABSTRACT: Alternative splicing (AS) of mRNA is a vital mechanism for enhancing genomic complexity in eukaryotes. Spliced isoforms of the same gene can have diverse molecular and biological functions and are often differentially expressed across various tissues, times, and conditions. Thus, AS has important implications in the study of parasitic nematodes with complex life cycles. Transcriptomic datasets are available from many species, but data must be revisited with splice-aware assembly protocols to facilitate the study of AS in helminthes. We sequenced cDNA from the model worm Caenorhabditis elegans using 454/Roche technology for use as an experimental dataset. Reads were assembled with Newbler software, invoking the cDNA option. Several combinations of parameters were tested and assembled transcripts were verified by comparison with previously reported C. elegans genes and transcript isoforms and with Illumina RNAseq data. Thoughtful adjustment of program parameters increased the percentage of assembled transcripts that matched known C. elegans sequences, decreased mis-assembly rates (i.e., cis- and trans-chimeras), and improved the coverage of the geneset. The optimized protocol was used to update de novo transcriptome assemblies from nine parasitic nematode species, including important pathogens of humans and domestic animals. Our assemblies indicated AS rates in the range of 20-30%, typically with 2-3 transcripts per AS locus, depending on the species. Transcript isoforms from the nine species were translated and searched for similarity to known proteins and functional domains. Some 21 InterPro domains, including several involved in nucleotide and chromatin binding, were statistically correlated with AS genetic loci. In most cases, the Roche/454 data explored in this study are the only sequences available from the species in question; however, the recently published genome of the human hookworm Necator americanus provided an additional opportunity to validate our results. Our optimized assembly parameters facilitated the first survey of AS among parasitic nematodes. The nine transcriptome assemblies, their protein translations, and basic annotations are available from as a resource for the research community. These should be useful for studies of specific genes and gene families of interest as well as for curating draft genome assemblies as they become available.
    Parasites & Vectors 04/2014; 7(1):151. DOI:10.1186/1756-3305-7-151 · 3.43 Impact Factor
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