Microsporidian genome analysis reveals evolutionary strategies for obligate intracellular growth

Abstract

Microsporidia comprise a large phylum of obligate intracellular eukaryotes that are fungal-related parasites responsible for widespread disease, and here we address questions about microsporidia biology and evolution. We sequenced three microsporidian genomes from two species, Nematocida parisii and Nematocida sp1, which are natural pathogens of Caenorhabditis nematodes and provide model systems for studying microsporidian pathogenesis. We performed deep sequencing of transcripts from a time course of N. parisii infection. Examination of pathogen gene expression revealed compact transcripts and a dramatic takeover of host cells by Nematocida. We also performed phylogenomic analyses of Nematocida and other microsporidian genomes to refine microsporidian phylogeny and identify evolutionary events of gene loss, acquisition, and modification. In particular, we found that all microsporidia lost the tumor-suppressor gene retinoblastoma, which we speculate could accelerate the parasite cell cycle and increase the mutation rate. We also found that microsporidia acquired transporters that could import nucleosides to fuel rapid growth.

Annotation of microsporidian genomes using transcriptional signals

“…Such diversity could be related to the fact that A. algerae is able to infect both mammals and insect hosts. This diversity also suggests an increased host dependency, which is not in accordance with O. bayeri proteomic data, and suggests an increased genome complexity related to reduced host dependency 16 . Furthermore, the metabolic patterns of how the insect and mammalian stages of the parasite acquire amino acids and other nutrients are unknown, suggesting that the detected transporter genes need to be elucidated by further bench work on the precise metabolic pathways.…”

“…Such sequence variability has also been previously observed by sequencing cloned PCR products from A. algerae and also A. locustae 35 . Sequence polymorphisms have recently been described in the Nematocida genus 16 . Indeed, these authors have identified SNPs preferentially located in coding regions that generate synonymous codons.…”

“…Most of this variation can be attributed to length variations of intergenic regions and to the number of repeat sequences and TEs. In addition, genome size variations in microsporidia may also be a consequence of variations in the size of telomere repeats, as suggested by the O. bayeri sequencing project 16 .…”

“…Its genome, however, is still poorly documented 8 . Moreover, comparative genomic analysis using currently available microsporidian genomic data from other fully sequenced genomes (that is, Encephalitozoon cuniculi 9 , Encephalitozoon intestinalis 10 , Enterocytozoon bieneusi 11,12 , Nosema ceranae 13 Octosporea bayeri 14 and more recently, Encephalitozoon romaleae 15 , Encephalitozoon hellem 15 , Nematocida parisii 16 and Nematocida sp1 16 ) will provide a better understanding of specific host-parasite interactions and adaptation capacities.…”

The genome of an Encephalitozoon cuniculi type III strain reveals insights into the genetic diversity and mode of reproduction of a ubiquitous vertebrate pathogen

“…Homologs of genes involved in conserved biochemical pathways are few in microsporidia compared with other eukaryotes; a feature that highlights their dependence on host cells for metabolic supplies . Finally, most genome studies of species with mononucleated spores have revealed evidence of diploidy in microsporidia (Katinka et al, 2001;Cuomo et al, 2012;Selman et al, 2013;Desjardins et al, 2015;Watson et al, 2015), although recent analyses of diplokaryotic species have suggested that polyploidy can also occur in this group (Pelin et al, 2015).…”