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

Genome Res. 2010 Aug;20(8):1112-21. doi: 10.1101/gr.100099.109. Epub 2010 Jul 6.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Helminth Proteins

Associated data

  • GENBANK/GU258169
  • GENBANK/GU258170
  • GENBANK/GU258171
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  • GENBANK/GU258219
  • GEO/GPL10466
  • GEO/GSE22037