The compact genome of reveals important steps in the evolution of intestinal protozoan parasites.

Diplomonad parasites of the genus have adapted to colonizing different hosts, most notably the intestinal tract of mammals. The human-pathogenic species, , has been extensively studied at the genome and gene expression level, but no such information is available for other species. Comparative data would be particularly valuable for , which colonizes mice and is commonly used as a prototypic model for investigating host responses to intestinal parasitic infection. Here we report the draft-genome of . We discovered a highly streamlined genome, amongst the most densely encoded ever described for a nuclear eukaryotic genome. and share many known or predicted virulence factors, including cysteine proteases and a large repertoire of cysteine-rich surface proteins involved in antigenic variation. Different to , maintains tandem arrays of pseudogenized surface antigens at the telomeres, whereas intact surface antigens are present centrally in the chromosomes. The two classes of surface antigens engage in genetic exchange. Reconstruction of metabolic pathways from the genome suggest significant metabolic differences to . Additionally, encodes proteins that might be used to modulate the prokaryotic microbiota. The responsible genes have been introduced in the genus via lateral gene transfer from prokaryotic sources. Our findings point to important evolutionary steps in the genus as it adapted to different hosts and it provides a powerful foundation for mechanistic exploration of host-pathogen interaction in the -mouse pathosystem.