Comparative genomics of the parasite Trichomonas vaginalis reveals genes involved in spillover from birds to humans

Trichomonas vaginalis, the causative agent of the venereal disease trichomoniasis, infects men and women globally and is associated with serious outcomes during pregnancy, increased risk of HIV-1 infection, and cancers of the human reproductive tract. Species of trichomonad parasitize a range of hosts in addition to humans, including birds, livestock, and pets. Genetic analysis of trichomonads recovered from columbid birds has provided evidence that they undergo frequent host-switching, and that a spillover event from columbids likely gave rise to T. vaginalis in humans. Here we describe a comparative genomics study of seven trichomonad species, generating chromosome-scale reference genomes for T. vaginalis and its avian sister species Trichomonas stableri, and assemblies of five other species that infect birds and mammals. Human-infecting trichomonad lineages have undergone recent and convergent genome size expansions compared to their avian sister species, a result of extensive repeat expansions specifically of multicopy gene families and transposable elements, with genetic drift likely a driver due to relaxed selection. Trichomonads are thought to have independently host-switched twice from birds to mammals/humans. We identify gene functions implicated in the transition, including host tissue adherence and phagocytosis, extracellular vesicle formation, and CAZyme virulence factors, which are all associated with pathogenesis phenotypes.