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

Genome Biol. 2004;5(6):R39. doi: 10.1186/gb-2004-5-6-r39. Epub 2004 May 18.

Abstract

Background: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans Proteins / genetics
  • Conserved Sequence / genetics
  • Evolution, Molecular*
  • Expressed Sequence Tags*
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism*
  • Nippostrongylus / genetics*
  • Parasites / metabolism*
  • Protein Sorting Signals / genetics*
  • Selection, Genetic
  • Sequence Analysis, Protein / methods*
  • Sequence Homology, Nucleic Acid
  • Trans-Splicing / genetics

Substances

  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • Protein Sorting Signals