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Signal sequence analysis of expressed sequence tags from the nematode Nippostrongylus brasiliensis and the evolution of secreted proteins in parasites

Yvonne M Harcus1, John Parkinson13, Cecilia Fernández14, Jennifer Daub1, Murray E Selkirk2, Mark L Blaxter1 and Rick M Maizels1*

Author Affiliations

1 Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh, EH9 3JT, UK

2 Department of Biological Sciences, Imperial College London, London SW7 2AZ, UK

3 Current address: Program in Genetics and Genomic Biology, Hospital for Sick Children, University Avenue, Toronto, Ontario M5G 1X8, Canada

4 Current address: Facultad de Química, Cátedra de Inmunología, Universita de la Republica, Montevideo 11300, Uruguay

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Genome Biology 2004, 5:R39  doi:10.1186/gb-2004-5-6-r39

Published: 18 May 2004



Parasitism is a highly successful mode of life and one that requires suites of gene adaptations to permit survival within a potentially hostile host. Among such adaptations is the secretion of proteins capable of modifying or manipulating the host environment. Nippostrongylus brasiliensis is a well-studied model nematode parasite of rodents, which secretes products known to modulate host immunity.


Taking a genomic approach to characterize potential secreted products, we analyzed expressed sequence tag (EST) sequences for putative amino-terminal secretory signals. We sequenced ESTs from a cDNA library constructed by oligo-capping to select full-length cDNAs, as well as from conventional cDNA libraries. SignalP analysis was applied to predicted open reading frames, to identify potential signal peptides and anchors. Among 1,234 ESTs, 197 (~16%) contain predicted 5' signal sequences, with 176 classified as conventional signal peptides and 21 as signal anchors. ESTs cluster into 742 distinct genes, of which 135 (18%) bear predicted signal-sequence coding regions. Comparisons of clusters with homologs from Caenorhabditis elegans and more distantly related organisms reveal that the majority (65% at P < e-10) of signal peptide-bearing sequences from N. brasiliensis show no similarity to previously reported genes, and less than 10% align to conserved genes recorded outside the phylum Nematoda. Of all novel sequences identified, 32% contained predicted signal peptides, whereas this was the case for only 3.4% of conserved genes with sequence homologies beyond the Nematoda.


These results indicate that secreted proteins may be undergoing accelerated evolution, either because of relaxed functional constraints, or in response to stronger selective pressure from host immunity.