Protein variation in blood-dwelling schistosome worms generated by differential splicing of micro-exon gene transcripts

Ricardo DeMarco, William Mathieson, Sophia J Manuel, Gary P Dillon, Rachel S Curwen, Peter D Ashton, Alasdair C Ivens, Matthew Berriman, Sergio Verjovski-Almeida, R Alan Wilson

Research output: Contribution to journalArticlepeer-review

Abstract

Schistosoma mansoni is a well-adapted blood-dwelling parasitic helminth, persisting for decades in its human host despite being continually exposed to potential immune attack. Here, we describe in detail micro-exon genes (MEG) in S. mansoni, some present in multiple copies, which represent a novel molecular system for creating protein variation through the alternate splicing of short (<or =36 bp) symmetric exons organized in tandem. Analysis of three closely related copies of one MEG family allowed us to trace several evolutionary events and propose a mechanism for micro-exon generation and diversification. Microarray experiments show that the majority of MEGs are up-regulated in life cycle stages associated with establishment in the mammalian host after skin penetration. Sequencing of RT-PCR products allowed the description of several alternate splice forms of micro-exon genes, highlighting the potential use of these transcripts to generate a complex pool of protein variants. We obtained direct evidence for the existence of such pools by proteomic analysis of secretions from migrating schistosomula and mature eggs. Whole-mount in situ hybridization and immunolocalization showed that MEG transcripts and proteins were restricted to glands or epithelia exposed to the external environment. The ability of schistosomes to produce a complex pool of variant proteins aligns them with the other major groups of blood parasites, but using a completely different mechanism. We believe that our data open a new chapter in the study of immune evasion by schistosomes, and their ability to generate variant proteins could represent a significant obstacle to vaccine development.
Original languageEnglish
Pages (from-to)1112-21
Number of pages10
JournalGenome Research
Volume20
Issue number8
DOIs
Publication statusPublished - Aug 2010

Keywords

  • Schistosoma mansoni
  • Animals
  • Biological Evolution
  • Exons
  • Amino Acid Sequence
  • Transcription, Genetic
  • Base Sequence
  • Alternative Splicing
  • Proteomics
  • Molecular Sequence Data
  • Helminth Proteins
  • Up-Regulation
  • Sequence Homology, Amino Acid

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