Unusual inheritance of a functional <i>cki</i> homolog in the human pathogen <i>Schistosoma mansoni</i>.

Abstract

Schistosomes, parasitic flatworms responsible for the neglected tropical disease schistosomiasis, are protected by a skin-like tegument, and tegument maintenance is controlled by a schistosome ortholog (<i>p53-1</i>) of the tumor suppressor TP53. To understand <i>p53-1</i> function, we characterized a schistosome cyclin-dependent kinase inhibitor homolog (<i>cki</i>). Knockdown of <i>cki</i> resulted in hyperproliferation that, combined with <i>p53-1</i> knockdown, yielded tumor-like growths, indicating that <i>cki</i> and <i>p53-1</i> are tumor suppressors in <i>Schistosoma mansoni</i>. <i>cki</i> homologs are ubiquitous in parasitic flatworms but are absent from their free-living ancestors, suggesting that <i>cki</i> may have come from horizontal gene transfer. This suggests that the evolution of parasitism in flatworms was aided by an unusual means of metazoan genetic inheritance.