Trichinella spiralis: Adaptation and parasitism

Publication of the genome from the clade I organism, Trichinella spiralis, has provided us an avenue to address more holistic problems in parasitology; namely the processes of adaptation and the evolution of parasitism. Parasitism among nematodes has evolved in multiple, independent events. Deciphering processes that drive species diversity and adaptation are keys to understanding parasitism and advancing control strategies. Studies have been put forth on morphological and physiological aspects of parasitism and adaptation in nematodes; however, data is now coming available to investigate adaptation, host switching and parasitism at the genomic level. Herein we compare proteomic data from the clade I parasite, Trichinella spiralis with data from Brugia malayi (clade III), Meloidogyne hapla and Meloidogyne incognita (clade IV), and free-living nematodes belonging to the genera Caenorhabditis and Pristionchus (clade V). We explore changes in protein family birth/death and expansion/reduction over the course of metazoan evolution using Homo sapiens, Drosophila melanogaster and Saccharomyces cerevisiae as out- groups for the phylum Nematoda. We further examine relationships between these changes and the ability and/or result of nematodes adapting to their environments. Data are consistent with gene loss occurring in conjunction with nematode specialization resulting from parasitic worms acclimating to well-defined, environmental niches. We observed evidence for independent, lateral gene transfer events involving conserved genes that may have played a role in the evolution of nematode parasitism. In general, parasitic nematodes gained proteins through duplication and lateral gene transfer, and lost proteins through random mutation and deletions. Data suggest independent acquisition rather than ancestral inheritance among the Nematoda followed by selective gene loss over evolutionary time. Data also show that parasitism and adaptation affected a broad range of proteins, especially those involved in sensory perception, metabolism, and transcription/translation. New protein gains with functions related to regu- lating transcription and translation, and protein family expansions with functions related to morphology and body development have occurred in association with parasitism. Further gains occurred as a result of lateral gene transfer and in particular, with the cyanase protein family In contrast, reductions and/or losses have occurred in protein families with functions related to metabolic process and signal trans- duction. Taking advantage of the independent occurrences of parasitism in nematodes, which enabled us to distinguish changes associated with parasitism from species specific niche adaptation, our study provides valuable insights into nematode parasitism at a proteome level using T. spiralis as a benchmark for early adaptation to or acquisition of parasitism

Genome sequence of Christensenella minuta DSM 22607T

Obesity influences and is influenced by the human gut microbiome. Here, we present the genome of Christensenella minuta, a highly heritable bacterial species which has been found to be strongly associated with obesity through an unknown biological mechanism. This novel genome provides a valuable resource for future obesity therapeutic studies

Cell death and transcriptional responses induced in larvae of the nematode Haemonchus contortus by toxins/toxicants with broad phylogenetic efficacy

Establishing methods to investigate treatments that induce cell death in parasitic nematodes will promote experimental approaches to elucidate mechanisms and to identify prospective anthelmintics capable of inducing this outcome. Here, we extended recent progress on a method to monitor cell death and to identify small molecule inhibitors i

Expressed sequence tags from life cycle stages of Trichinella spiralis: Application to biology and parasite control

While the approach taken to date to study Trichinella spp., involves mainly characterization of individual genes of interest, we initiated a genomics approach as an antecedent to more complete genome sequencing. Our approach involves use of expressed sequence tags (ESTs) obtained from three life cycle stages of Trichinella spiralis; adult worms (AD), mature muscle larvae (ML) and immature L1 larvae (immL1, also known as newborn larvae) (Mitreva et al., 2004a) to improve the technical capacity for research on Trichinella spp. and to generate information that will aid prospective development of relevant hypotheses. In this review, we will summarize findings of our EST analysis and discuss how they relate to topics mentioned above. The foundation laid by this data will also contribute toward development of a more substantial genomic database and technical capacity to dissect molecular interactions between vertebrate hosts and Trichinella spp

Identification and characterization of alternative splicing in parasitic nematode transcriptomes

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 Nematode.net 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

Pan-phylum comparison of nematode metabolic potential

<div><p>Nematodes are among the most important causative pathogens of neglected tropical diseases. The increased availability of genomic and transcriptomic data for many understudied nematode species provides a great opportunity to investigate different aspects of their biology. Increasingly, metabolic potential of pathogens is recognized as a critical determinant governing their development, growth and pathogenicity. Comparing metabolic potential among species with distinct trophic ecologies can provide insights on overall biology or molecular adaptations. Furthermore, ascertaining gene expression at pathway level can help in understanding metabolic dynamics over development. Comparison of biochemical pathways (or subpathways, i.e. pathway modules) among related species can also retrospectively indicate potential mistakes in gene-calling and functional annotation. We show with numerous illustrative case studies that comparisons at the level of pathway modules have the potential to uncover biological insights while remaining computationally tractable. Here, we reconstruct and compare metabolic modules found in the deduced proteomes of 13 nematodes and 10 non-nematode species (including hosts of the parasitic nematode species). We observed that the metabolic potential is, in general, concomitant with phylogenetic and/or ecological similarity. Varied metabolic strategies are required among the nematodes, with only 8 out of 51 pathway modules being completely conserved. Enzyme comparison based on topology of metabolic modules uncovered diversification between parasite and host that can potentially guide therapeutic intervention. Gene expression data from 4 nematode species were used to study metabolic dynamics over their life cycles. We report unexpected differential metabolism between immature and mature microfilariae of the human filarial parasite <i>Brugia malayi</i>. A set of genes potentially important for parasitism is also reported, based on an analysis of gene expression in <i>C</i>. <i>elegans</i> and the human hookworm <i>Necator americanus</i>. We illustrate how analyzing and comparing metabolism at the level of pathway modules can improve existing knowledge of nematode metabolic potential and can provide parasitism related insights. Our reconstruction and comparison of nematode metabolic pathways at a pan-phylum and inter-phylum level enabled determination of phylogenetic restrictions and differential expression of pathways. A visualization of our results is available at <a href="http://nematode.net" target="_blank">http://nematode.net</a> and the program for identification of module completeness (modDFS) is freely available at SourceForge. The methods reported will help biologists to predict biochemical potential of any organism with available deduced proteome, to direct experiments and test hypotheses.</p></div

Editorial: Novel Frontiers in Helminth Genomics

No abstract available