@article{DeMarco01082010, author = {DeMarco, Ricardo and Mathieson, William and Manuel, Sophia J. and Dillon, Gary P. and Curwen, Rachel S. and Ashton, Peter D. and Ivens, Alasdair C. and Berriman, Matthew and Verjovski-Almeida, Sergio and Wilson, R. Alan}, title = {Protein variation in blood-dwelling schistosome worms generated by differential splicing of micro-exon gene transcripts}, volume = {20}, number = {8}, pages = {1112-1121}, year = {2010}, doi = {10.1101/gr.100099.109}, 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 (≤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.}, URL = {http://genome.cshlp.org/content/20/8/1112.abstract}, eprint = {http://genome.cshlp.org/content/20/8/1112.full.pdf+html}, journal = {Genome Research} }