Although free-living species display a high propensity for symbioses spanning the spectrum from commensalism to parasitism, there is strong evidence that the major parasitic lineages form a monophyletic group, demonstrating that obligate parasitism arose only once during the course of flatworm evolution (11). This was associated with a major developmental shift involving the separation of ontogenetically distinct

larval and adult stages, with replacement of the larval epidermis by a syncytial tegument. Within this clade, we now recognize four independent lineages: the cestodes (tapeworms), digeneans (flukes) and monopisthocotylean and polyopisthocotylean ‘monogeneans’. Interrelationships of these lineages remain controversial, but have begun to point toward a sister relationship between cestodes and digeneans, BMN 673 and paraphyly of the ‘Monogenea’ (11,14,15), in contrast to previous hypotheses (and classifications) that considered ‘monogeneans’ to be both monophyletic and the sister group to tapeworms. The main implications of the molecular-based hypotheses are a common origin of both enteric parasitism and complex life cycles in tapeworms MG132 and flukes despite major differences in their life histories, and that the first neodermatan flatworms were nonenteric and direct-developing, as seen in contemporary monopisthocotylean

and polyopisthocotylean parasites. Only in the last two decades science has our understanding of tapeworm interrelationships begun to stabilize, thanks to a more concerted effort on the part of cestodologists (16) and the wide application of molecular phylogenetic techniques (14). Circumscription of even the primary tapeworm lineages has required major revisions to reflect new insights into their affinities, resulting in the proposal of three new tapeworm orders since 2008 (17,18). Interrelationships of the 15 or more natural (i.e. monophyletic) groups of tapeworms

have yet to be resolved satisfactorily, but it is clear that early branching lineages colonized a wide spectrum of cartilaginous and bony fishes before subsequent diversification led to the colonization of homeothermic hosts (e.g. birds, mammals) (19–21). Among the early branching groups, only the Diphyllobothriidea [n.b. formally classified as a family of Pseudophyllidea (18)] radiated into homeotherms, but retained its association with fishes (which became 2nd intermediate hosts) and transmission via aquatic life cycles (22). There was thus a single primary colonization of homeothermic hosts coincident with the adoption of fully terrestrial life cycles that gave rise to the most speciose contemporary group, the Cyclophyllidea. The extent to which tapeworm–host associations were shaped by the unique adaptive immunity of the mammalian host is not clear from an evolutionary perspective.