RT Journal Article SR Electronic T1 The compact genome of Giardia muris reveals important steps in the evolution of intestinal protozoan parasites JF bioRxiv FD Cold Spring Harbor Laboratory SP 870949 DO 10.1101/870949 A1 Feifei Xu A1 Alejandro Jiménez-González A1 Elin Einarsson A1 Ásgeir Ástvaldsson A1 Dimitra Peirasmaki A1 Lars Eckmann A1 Jan O. Andersson A1 Staffan G. Svärd A1 Jon Jerlström-Hultqvist YR 2019 UL http://biorxiv.org/content/early/2019/12/10/870949.abstract AB Diplomonad parasites of the genus Giardia have adapted to colonizing different hosts, most notably the intestinal tract of mammals. The human-pathogenic Giardia species, Giardia intestinalis, has been extensively studied at the genome and gene expression level, but no such information is available for other Giardia species. Comparative data would be particularly valuable for Giardia muris, which colonizes mice and is commonly used as a prototypic in vivo model for investigating host responses to intestinal parasitic infection. Here we report the draft-genome of G. muris. We discovered a highly streamlined genome, amongst the most densely encoded ever described for a nuclear eukaryotic genome. G. muris and G. intestinalis 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 G. intestinalis, G. muris 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 G. muris genome suggest significant metabolic differences to G. intestinalis. Additionally, G. muris encodes proteins that might be used to modulate the prokaryotic microbiota. The responsible genes have been introduced in the Giardia genus via lateral gene transfer from prokaryotic sources. Our findings point to important evolutionary steps in the Giardia genus as it adapted to different hosts and it provides a powerful foundation for mechanistic exploration of host-pathogen interaction in the G. muris – mouse pathosystem.Importance The Giardia genus comprises eukaryotic single-celled parasites that infect many animals. The Giardia intestinalis species complex, which can colonize and cause diarrheal disease in humans and different animal hosts has been extensively explored at the genomic and cell biologic levels. Other Giardia species, such as the mouse parasite Giardia muris, have remained uncharacterized at the genomic level, hampering our understanding of in vivo host-pathogen interactions and the impact of host dependence on the evolution of the Giardia genus. We discovered that the G. muris genome encodes many of the same virulence factors as G. intestinalis. The G. muris genome has undergone genome contraction, potentially in response to a more defined infective niche in the murine host. We describe differences in metabolic and microbiome modulatory gene repertoire, mediated mainly by lateral gene transfer, that could be important for understanding infective success across the Giardia genus. Our findings provide new insights for the use of G. muris as a powerful model for exploring host-pathogen interactions in giardiasis.