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

Abstract

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.