TY  - JOUR
A1  - DeMarco, Ricardo
A1  - Mathieson, William
A1  - Manuel, Sophia J.
A1  - Dillon, Gary P.
A1  - Curwen, Rachel S.
A1  - Ashton, Peter D.
A1  - Ivens, Alasdair C.
A1  - Berriman, Matthew
A1  - Verjovski-Almeida, Sergio
A1  - Wilson, R. Alan
T1  - Protein variation in blood-dwelling schistosome worms generated by differential splicing of micro-exon gene transcripts
Y1  - 2010/08/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1112 
EP  - 1121 
DO  - 10.1101/gr.100099.109 
VL  - 20 
IS  - 8 
UR  - http://genome.cshlp.org/content/20/8/1112.abstract 
N2  - 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. 
ER  -