Protein variation in blood-dwelling schistosome worms generated by differential splicing of micro-exon gene transcripts.
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.
DeMarco
Ricardo
R
Department of Biology, University of York, York YO10 5YW, United Kingdom. rdemarco@ifsc.usp.br
Mathieson
William
W
Manuel
Sophia J
SJ
Dillon
Gary P
GP
Curwen
Rachel S
RS
Ashton
Peter D
PD
Ivens
Alasdair C
AC
Berriman
Matthew
M
Verjovski-Almeida
Sergio
S
Wilson
R Alan
RA
D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D005091:Exons; D015801:Helminth Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D040901:Proteomics; D012550:Schistosoma mansoni / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D015854:Up-Regulation
D015801:Helminth Proteins