Representation of an immune responsive gene family encoding fibrinogen-related proteins in the freshwater mollusc Biomphalaria glabrata, an intermediate host for Schistosoma mansoni

Zhang, Si-Ming; Loker, Eric S.

doi:10.1016/j.gene.2004.07.003

Cited by 83 publications

(75 citation statements)

References 33 publications

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“…Diversity in the sequence encoding the N-terminal immunoglobulin-like domain of FREP3 is three-to fourfold higher than in control, unrelated genes. Taken together, a mathematical estimate and Southern-blot data indicate that a specific number of germline sequences are maintained across each subfamily and could account for all of the known variation, including nucleotide changes and diversification through recombination 8,129 . The observed diversity in FREP3 cDNAs probably derives from somatic modification of FREP3 genes 8 .…”

Section: Variation In Invertebrate Immune Receptorsmentioning

confidence: 99%

Reconstructing immune phylogeny: new perspectives

2005

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Numerous studies of the mammalian immune system have begun to uncover profound interrelationships, as well as fundamental differences, between the adaptive and innate systems of immune recognition. Coincident with these investigations, the increasing experimental accessibility of non-mammalian jawed vertebrates, jawless vertebrates, protochordates and invertebrates has provided intriguing new information regarding the likely patterns of emergence of immune-related molecules during metazoan phylogeny, as well as the evolution of alternative mechanisms for receptor diversification. Such findings blur traditional distinctions between adaptive and innate immunity and emphasize that, throughout evolution, the immune system has used a remarkably extensive variety of solutions to meet fundamentally similar requirements for host protection.The evolutionary development of the METAZOANS was associated with the diversification of a wide range of specialized cell-surface molecules that mediate key metabolic processes, as well as provide crucial contact interfaces and carry out a broad range of other essential functions. It is not unexpected that some of these molecules also came to function as barriers to pathogenic invasion and, in doing so, began to carry out dedicated innate immune protective functions. Whereas the simplest form of protection, barrier formation, is essentially mechanical in nature, relentless pressure from genetic variation in pathogens probably drove the evolution of such innate immune protective molecules towards diversification and, in parallel, towards integration of signalling pathways to regulate cellular responses to external stimulation. However, despite the sophistication that such innate immune mediators achieved over time, their biological complexity, by definition, would be limited by genome space, so with increasing complexity of body plan and/or increasing pathogen sophistication, they could be overwhelmed. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMore than 500 million years ago, a TRANSPOSITION event, probably involving a recombinationactivating gene (RAG)-bearing element, might have given rise to the predecessors of the rearranging antigen-binding receptors of the jawed vertebrates, which encompass the vertebrate radiations that extend from the cartilaginous fish through to humans. This is considered the defining point in the emergence of RAG-mediated (conventional) adaptive immunity 1,2 , which has evolved to create a mechanism for deriving almost limitless variation from very few genes. Studies in traditional and non-traditional animal models, such as sharks, bony fish and birds, have brought this event and its ramifications for host defence into sharper focus. We can now predict much about how these rearranging antigenbinding receptors probably arose, what alternative pathways of immune-receptor gene evolution have occurred, what relationships exist between B-and T-cell-mediated immunity and natural killer (NK)-cell function, how complex immune ...

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Section: Variation In Invertebrate Immune Receptorsmentioning

confidence: 99%

Reconstructing immune phylogeny: new perspectives

2005

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“…The primers used for generating FREP2 dsRNA (537 bp) were: forward 5′-TAATACGACTCACTATAGGGTCGCTACCACTTCGACTTGTT-3′, reverse 5′-TAATACGACTCACTATAGGGCGTGGGACTGGCTCTTGATAT-3′.The sequence underlined is T7 promoter sequence (same for myoglobin primers below). The primers span the region that encodes the signal peptide (SP), IgSF, and interceding region (ICR) of FREP2, a region known to be specific to this particular FREP gene [35]. A full-length FREP2 cDNA was cloned from M line snails and the sequence was confirmed by sequencing.…”

Section: Dsrna Synthesismentioning

confidence: 99%

“…RNA was separated on a 1% formaldehyde agarose gel. Electrophoresis and RNA transfer, hybridization, and blotwashing were performed according to the supplier's instruction (NorthernMax TM System, Ambion) with modifications suggested by Zhang and Loker [35]. The FREP2 probe used in this study is identical to the FREP2 probe previously used [35].…”

Section: Northern Blotsmentioning

confidence: 99%

“…Previous work suggests that FREPs are involved in molluscan internal defense because they are capable of precipitating soluble trematode antigens and binding to trematode sporocysts. Although considerable data on the structure, diversity, and expression of FREPs have accumulated recently [32][33][34][35][36], the precise roles of FREPs in defense and perhaps other aspects of snail physiology require further clarification. Classical genetic knockout techniques are not presently available in mollusks, nor are they likely to soon be developed.…”

Section: Introductionmentioning

confidence: 99%

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In vivo and in vitro knockdown of FREP2 gene expression in the snail Biomphalaria glabrata using RNA interference

Jiang

Loker

Zhang

2006

Developmental & Comparative Immunology

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RNA interference (RNAi) is reported here for the first time for Biomphalaria glabrata, the snail intermediate host for the human parasite Schistosoma mansoni. The fibrinogen-related protein 2 (FREP2) gene, normally expressed at increased levels following exposure to digenetic trematode parasites, such as S. mansoni or Echinostoma paraensei, was targeted for knockdown. Doublestranded RNA (dsRNA) corresponding to specific regions of the FREP2 gene was introduced into snails by direct injection into the hemolymph, 2 days prior to exposure to trematodes, or added to co-cultures of B. glabrata embryonic (Bge) cells and E. paraensei sporocysts. After introduction of FREP2 dsRNA, expression levels of FREP2 were significantly reduced, to 20-30% of control values. In addition, we were able to disrupt expression of the house-keeping myoglobin gene, further confirming the feasibility of RNAi for B. glabrata. Cross-reactivity in RNAi has not been observed either among four FREP gene subfamilies or between FREP2 and myoglobin. Establishment of RNAi techniques in B. glabrata provides an important tool for clarifying the function of genes believed to play a role in host-parasite interactions, specifically between B. glabrata and its trematode parasites, including S. mansoni.

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“…The first family, the set of Fibrinogen-related protein (FREP) genes from the snail Biomphalaria glabrata are medically relevant because this snail is a model organism for infection by the human-affecting parasite Schistosoma mansoni [16,17]. The second family, the olfactory genes of nematode Caenorhabditis elegans, is an excellent model for studies of chemosensation [38].…”

Section: Introductionmentioning

confidence: 99%

Efficient RNAi-based gene family knockdown via set cover optimization

Zhao

Fanning

Lane

2005

Artificial Intelligence in Medicine

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RNA interference (RNAi) is a recently discovered genetic immune system with widespread therapeutic and genomic applications. In this paper, we address the problem of selecting an efficient set of initiator molecules (siRNAs) for RNAi-based gene family knockdown experiments. Our goal is to select a minimal set of siRNAs that (a) cover a targeted gene family or a specified subset of it, (b) do not cover any untargeted genes, and (c) are individually highly effective at inducing knockdown. We show that the problem of minimizing the number of siRNAs required to knock down a family of genes is NP-Hard via a reduction to the set cover problem. We also give a formal statement of a generalization of the basic problem that incorporates additional biological constraints and optimality criteria. We modify the classical branch-and-bound algorithm to include some of these biological criteria. We find that, in many typical cases, these constraints reduce the search space enough that we are able to compute exact minimal siRNA covers within reasonable time. For larger cases, we propose a probabilistic greedy algorithm for finding minimal siRNA covers efficiently. Our computational results on real biological data show that the probabilistic greedy algorithm produces siRNA covers as good as the branch-andbound algorithm in most cases. Both algorithms return minimal siRNA covers with high predicted probability that the selected siRNAs will be effective at inducing knockdown. We also examine the role of "off-target" interactions -the constraint of avoiding covering untargeted genes can, in some cases, substantially increase the complexity of the resulting solution. Overall, however, we find that in many common cases, our approach significantly reduces the number of siRNAs required in gene family knockdown experiments, as compared to knocking down genes independently.

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Representation of an immune responsive gene family encoding fibrinogen-related proteins in the freshwater mollusc Biomphalaria glabrata, an intermediate host for Schistosoma mansoni

Cited by 83 publications

References 33 publications

Reconstructing immune phylogeny: new perspectives

Reconstructing immune phylogeny: new perspectives

In vivo and in vitro knockdown of FREP2 gene expression in the snail Biomphalaria glabrata using RNA interference

Efficient RNAi-based gene family knockdown via set cover optimization

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