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

Abstract

<jats:p>Diplomonad parasites of the genus <jats:italic>Giardia</jats:italic> have adapted to colonizing different hosts, most notably the intestinal tract of mammals. The human-pathogenic <jats:italic>Giardia</jats:italic> species, <jats:italic>Giardia intestinalis</jats:italic>, has been extensively studied at the genome and gene expression level, but no such information is available for other <jats:italic>Giardia</jats:italic> species. Comparative data would be particularly valuable for <jats:italic>Giardia muris</jats:italic>, which colonizes mice and is commonly used as a prototypic <jats:italic>in vivo</jats:italic> model for investigating host responses to intestinal parasitic infection. Here we report the draft-genome of <jats:italic>G. muris</jats:italic>. We discovered a highly streamlined genome, amongst the most densely encoded ever described for a nuclear eukaryotic genome. <jats:italic>G. muris</jats:italic> and <jats:italic>G. intestinalis</jats:italic> 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 <jats:italic>G. intestinalis</jats:italic>, <jats:italic>G. muris</jats:italic> 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 <jats:italic>G. muris</jats:italic> genome suggest significant metabolic differences to <jats:italic>G. intestinalis</jats:italic>. Additionally, <jats:italic>G. muris</jats:italic> encodes proteins that might be used to modulate the prokaryotic microbiota. The responsible genes have been introduced in the <jats:italic>Giardia</jats:italic> genus via lateral gene transfer from prokaryotic sources. Our findings point to important evolutionary steps in the <jats:italic>Giardia</jats:italic> genus as it adapted to different hosts and it provides a powerful foundation for mechanistic exploration of host–pathogen interaction in the <jats:italic>G. muris</jats:italic>–mouse pathosystem.</jats:p>

A free-living protist that lacks canonical eukaryotic DNA replication and segregation systems

“…The high contiguity of the assembly is underscored by the large number of transcripts mapped to single contigs (90.2%), and since the proteins encoded by transcripts were consistently found in the predicted proteome, the latter is also considered to be of high quality. We also conducted BUSCO analyses, with the foreknowledge that genomic streamlining typical in Metamonada has led to the loss of many conserved proteins 17,24,25 .…”

“…Despite using a phylogeny-guided search with the Eukaryota database, a more comprehensive database than the protist BUSCO database, a remarkably large number of BUSCO proteins were inconsistently present in Metamonada. This is not surprising, as the clade harbors a very diverse group of taxa with varied lifestyles and many have undergone genome streamlining 9,10,[23][24][25] , and the BUSCO databases are expected to be more accurate with greater taxonomic proximity to the studied genome 1,26,27 . While it might be tempting to suggest the 101 BUSCO proteins that are shared by all metamonads be used to evaluate genome completion in the clade, the overwhelming evidence of differential genome streamlining strongly indicates that databases should be lineage specific (e.g., Carpediemonas, Giardia, etc).…”

Metabolic Reconstruction Elucidates the Lifestyle of the Last Diplomonadida Common Ancestor

“… Giardia intestinalis WB lost the ability to degrade arginine to l -ornithine and urea, making the deimination of arginine to l -citrulline the only option to degrade this amino acid. Giardia intestinalis GS B shared the ability to degrade arginine through two different pathways with G. muris ( 30 ). On the other hand, G. intestinalis GS B lost the synthesis of glycine from glyoxylate.…”

“…The absence of those pathways suggested that G. muris is highly dependent on a supply of nucleosides and nucleotides, especially purines, from the environment within the host. On the other hand, G. muris can synthesize coenzyme A de novo ( 30 ). Our analysis suggested that the genes responsible for the synthesis of coenzyme A in G. muris were acquired independently in the lineages leading to G. muris and S. salmonicida ( Fig.…”

“…Any reaction with a majority of hits from prokaryotes was considered an LGT candidate. Reactions whose evolutionary history has been described previously were manually curated to be consistent ( 14 , 28 , 30 ). Classifications of all reactions are listed in Table S1 in the supplemental material.…”