Horizontal gene transfer of a functional cki homolog in the human pathogen Schistosoma mansoni .

Schistosomes are parasitic flatworms responsible for the neglected tropical disease schistosomiasis, causing devastating morbidity and mortality in the developing world. The parasites are protected by a skin-like tegument, and maintenance of this tegument is controlled by a schistosome ortholog of the tumor suppressor TP53. To understand mechanistically how p53-1 controls tegument production, we identified a cyclin dependent kinase inhibitor homolog ( cki ) that was co-expressed with p53-1 . RNA interference of cki resulted in a hyperproliferation phenotype, that, in combination with p53-1 RNA interference yielded abundant tumor-like growths, indicating that cki and p53-1 are bona fide tumor suppressors in Schistosoma mansoni . Interestingly, cki homologs are widely present throughout parasitic flatworms but evidently absent from their free-living ancestors, suggesting this cki homolog came from an ancient horizontal gene transfer event. This in turn implies that the evolution of parasitism in flatworms may have been aided by a highly unusual means of metazoan genetic inheritance.