Can Specialized Pathogens Colonize Distantly Related Hosts? Schistosome Evolution as a Case Study

P arasites that live in intimate contact with the immune system of their hosts require specialized adaptations to survive in such exposed environments. Once adapted to these demanding environments, it seems such parasites could not easily switch to distantly related hosts [1], and, thus, would be good candidates to diversify congruently with their hosts, i.e., cospeciation. One of the best-known parasite groups is the schistosomes, digenetic (having alternating sexually and asexually reproducing generations in their life cycle) trematodes that live in the vascular system of their vertebrate hosts. Schistosomes achieve notoriety because six of the roughly 100 described species [2,3] cause schistosomiasis, a disease that afflicts 200 million people, mostly in tropical Africa. Schistosomiasis is usually chronic and debilitating in its course, with most of the pathogenesis caused not directly by the adult worms but by the eggs they produce. Eggs become lodged in the viscera and incite tissue responses, often causing pronounced enlargements in the liver and spleen, and abnormalities in blood flow through these organs. If worms colonize the urinary system, hematuria (blood in the urine) and kidney and bladder damage often result. Schistosomiasis negatively affects growth and productivity, and has largely underappreciated, insidious effects on the people with this disease. Adult worms can be killed by drugs, but the limited availability and high cost of these drugs and the potential for emergence of drug resistance are important concerns. Immunity is slow to develop, though hope for an effective vaccine remains high. Schistosomes infect birds or mammals, but one species, Griphobilharzia amoena, often considered the missing link in schistosome evolution, is known to infect freshwater crocodiles [4]. Schistosomes share the habit of living in a vascular habitat with other trematodes, including the Spirorchiidae of turtles and the Sanguinicolidae of fishes. Worms in these three families have two-host life cycles—a snail host and a vertebrate host—and also share a distinctive tegument, or body covering, consisting of two lipid bilayers instead of the typical single bilayer. The double bilayer is believed to be an adaptation for survival in the immunologically hostile environment of the blood [5]. Schistosomes differ from the other two families of blood flukes, though, by being dioecious (having separate male and female worms) and dimorphic (with the two sexes different in morphology), and by having specialized habitat requirements. The remarkable biology of schistosomes has precipitated considerable discussion regarding their origins and their evolution of dioecy (the change from the typical state in trematodes of being hermaphrodites to a state with separate males and females) [2,4,6–10]. The discovery of G. amoena [4], the only species of schistosome known in an ectotherm, gave rise to a hypothesis that schistosomes arose in early ectothermic archosaurs, for example, ancestors of modern crocodiles, and radiated into endothermic archosaurs (birds). This view was supported by a phylogenetic analysis of adult morphology, which placed G. amoena as basal, or ancestral, among schistosomes [11], and challenged the role of endothermy as the pivotal factor driving schistosome diversification [10–12]. Molecular phylogenetic studies to date [7,13,14] have been hampered by an incomplete sampling of the 13 widely recognized schistosome genera, including the provocative and putatively basal G. amoena. The molecular phylogeny in Figure 1 includes representatives of all the commonly recognized genera of schistosomes, and spirorchiids from both freshwater and marine turtles [7]. Included in this molecular phylogeny is G. amoena, specimens of which were recovered from the Australian freshwater crocodile, Crocodylus johnstoni, obtained near Darwin, Australia. Our analysis shows that G. amoena is, in fact, not a basal schistosome, but is more closely related to spirorchiids from freshwater turtles. This expands the host range of spirorchiids to include reptiles other than turtles, and suggests that schistosomes parasitize only endotherms. Our analysis confirms that the sister group to the schistosomes are the spirorchiids from marine turtles [7], and that the basal schistosomes are parasites ofmarine birds and snails (Figure 1). This pattern supports the idea that a long-range host switch from turtles to avian hosts occurred in marine habitats, and that schistosomes subsequently colonized birds, mammals, and freshwater snails. This argues against a hypothesis of a longterm association between schistosomes and archosaurs (crocodilians), and suggests that exploitation of endotherms has been the key factor leading to the emergence of schistosomes and their dioecious condition [2,8]. We speculate that the transferal of a spirorchiid protoschistosome to an