Trends in Parasitology
Volume 21, Issue 11, November 2005, Pages 533-536
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The molecular biology of schistosomes

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Twenty years ago, an article by Carter and Colley was published in an early issue of this journal. The report outlined pioneering studies by several laboratories into schistosome molecular biology and molecular genetics. To commemorate that prescient report and, in like fashion, to provide a brief (and non-comprehensive) synopsis of progress in this field up to the present time, I will outline some key aspects of the molecular biology of schistosomes that have been reported in the intervening years.

Section snippets

Tropical scourge

As many people today are affected by schistosomiasis as were 50 years ago, although where these infected people live has changed during these five decades, following changes in socioeconomic and political events; residents of sub-Saharan Africa endure the heaviest burden [1]. Moreover, a recent meta-analysis indicates that the burden of schistosomiasis is far greater than previously estimated, in terms of anaemia, chronic pain, diarrhoea, exercise intolerance and undernourishment (in addition

Genome and transcriptome

Schistosome species that infect humans include Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum and, to a lesser extent, Schistosoma intercalatum and Schistosoma mekongi. Of these, the African blood fluke S. mansoni and the Asian blood fluke S. japonicum have been characterized reasonably well at the genomic level. Schistosomes have comparatively large genomes, estimated to be ∼270 Mb for the haploid genome of S. mansoni, arrayed on seven pairs of autosomes and one pair of sex

Mobile genetic elements, other repetitive sequences and schistosome phylogeny

Between 40% and 60% of the schistosome genome seems to consist of repetitive sequences. Much of this repetitive component comprises mobile genetic elements that include the Merlin transposon, the SM-α SINE-like elements, long terminal repeat (LTR) retrotransposons such as Boudicca, and non-LTR retrotransposons, including SR2 and pido 14, 15, 16, 17, 18. As with other species, these mobile sequences have had a substantial influence on the evolution of the schistosome genome [19]. In addition,

Mitochondrial genome

Mitochondria accomplish the respiratory metabolism of eukaryote cells. The mitochondrial genomes of S. japonicum and S. mansoni have been sequenced, as have most of the mitochondrial genomes of Schistosoma malayensis, S. mekongi and S. haematobium, and sequences of informative loci from the mitochondrial genomes of several other flatworms are known [23]. The studies determining the sequences confirmed that the schistosome mitochondrial genome is small, circular and haploid, conforming to the

Signal transduction

In addition to functions predicted from transcriptomics analyses [8], many schistosome genes and proteins have been functionally characterized, including components of signal-transduction pathways. Much of the motivation for progress in research into signalling and the molecular biology of reproduction has been the understanding that female parasite development and reproduction are dependent on the presence of the male schistosome [24]. Genes that encode tegument-localized signal-transduction

Motility

Jones et al. [34] have reviewed the cytoskeleton and motor proteins at the surface of the human schistosomes, and their roles in surface maintenance and host–parasite interactions. Several genes and proteins associated with motility functions in schistosomes have been characterized in detail, including myosin, paramyosin, tropomyosin, actin, troponins and dynein light chains. Maule and co-workers have characterized neuropeptides that are central to signal transduction in the schistosome nervous

Nutrition

Schistosomes use amino acids from the digestion of host haemoglobin from ingested blood for growth, development and reproduction. Genes encoding haemoglobin-degrading hydrolases – including cathepsins B, C, D and L, and leucine aminopeptidase – and their recombinant forms and substrate preferences have been characterized 36, 37. Schistosome cells move amino acids and glucose across their surface membranes with the aid of transporter proteins that are localized in the parasite tegument 38, 39.

Molecular and cellular manipulation tools

Since Carter and Colley first reported on the availability of phage cDNA libraries [3], many other gene- and genome-manipulation tools for schistosome molecular genetics have been developed or deployed. These include bacterial artificial chromosome libraries containing manifold genome equivalents [43], gene microarrays [44], reporter systems for gene regulatory element analysis 45, 46, transcription factor analysis – including investigation of a Y-box-binding protein from S. mansoni [47] –

Drugs, vaccines and concluding remarks

Praziquantel (PZQ) is the drug of choice for treating all forms of schistosomiasis. Although PZQ was first used ∼25 years ago, the molecular basis of its antischistosomal action has not been elucidated fully. Greenberg et al. have characterized schistosome voltage-gated calcium channels and compared their molecular structures with homologous channels from other eukaryotes. These channels seem to have a key role in the action of PZQ [56]. The artemisinin derivative artemether also offers promise

Acknowledgements

I am a recipient of a Burroughs Wellcome Fund scholar award in molecular parasitology. Support from NIH/NIAID award number P50 AI39461–06A1 is gratefully acknowledged.

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